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Encyclopedia > Insulin
Insulin

Insulin crystals Note: This article title may be easily confused with insulin. ... Commons:Image:Insulincrystals. ...

Genetic data
Locus: Chr. 11 p15.5
Gene code: HUGO/INS
Gene type: Protein coding
Protein Structure/Function
Molecular Weight: 5808 (Da)
Structure: Solution Structure of Human pro-Insulin Polypeptide
Protein type: insulin family
Functions: glucose regulation
Domains: INS domain
Motifs: SP motif
Other
Taxa expressing: Homo sapiens; homologs: in metazoan taxa from invertebrates to mammals
Cell types: pancreas: beta cells of the Islets of Langerhans
Subcellular localization: extracellular fluids
Covalent modifications: glycation, proteolytic cleavage
Pathway(s): Insulin signaling pathway (KEGG); Type II diabetes mellitus (KEGG); Type I diabetes mellitus (KEGG); Maturity onset diabetes of the young (KEGG); Regulation of actin cytoskeleton (KEGG)
Receptor/Ligand data
Antagonists: glucagon, steroids, most stress hormomes
Medical/Biotechnological data
Diseases: familial hyperproinsulinemia, Diabetes mellitus
Pharmaceuticals: insulin (Humulin Novolin), insulin lispro (Humalog), insulin aspart (NovoLog), insulin detemir (Levemir), insulin glargine (Lantus), etc
Database Links
Codes: EntrezGene 3630; Mendelian Inheritance in Man (OMIM) 176730; UniProt P01308; RefSeq NM_000207

Insulin is an animal hormone whose presence informs the body's cells that the animal is well fed, causing liver and muscle cells to take in glucose and store it in the form of glycogen, and causing fat cells to take in blood lipids and turn them into triglycerides. In addition it has several other anabolic effects throughout the body. This article is about the general scientific term. ... Short and long arms Chromosome. ... Chromosome 11 is one of the 23 pairs of chromosomes in humans. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... The unified atomic mass unit (u), or dalton (Da), is a small unit of mass used to express atomic and molecular masses. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... Glucose (Glc), a monosaccharide (or simple sugar), is an important carbohydrate in biology. ... Within a protein, a structural domain (domain) is an element of overall structure that is self-stabilizing and often folds independently of the rest of the protein chain. ... In an unbranched, chain-like biological molecule, such as a protein or a strand of RNA, a structural motif is a three-dimensional structural element or fold within the chain, which appears also in a variety of other molecules. ... A taxon (plural taxa), or taxonomic unit, is a grouping of organisms (named or unnamed). ... Homo sapiens (Latin: wise man) is the scientific name for the human species. ... Phyla Subkingdom Parazoa Porifera (sponges) Subkingdom Agnotozoa Placozoa Orthonectida Rhombozoa Subkingdom Metazoa Radiata Cnidaria Ctenophora - Comb jellies Bilateria Protostomia Acoelomorpha Platyhelminthes - Flatworms Nemertina - Ribbon worms Gastrotricha Gnathostomulida - Jawed worms Micrognathozoa Rotifera - Rotifers Acanthocephala Priapulida Kinorhyncha Loricifera Entoprocta Nematoda - Roundworms Nematomorpha - Horsehair worms Cycliophora Mollusca - Mollusks Sipuncula - Peanut worms Annelida - Segmented... A taxon (plural taxa) is an element of a taxonomy, e. ... There are about 210 distinct human cell types. ... The pancreas is a gland organ in the digestive and endocrine systems of vertebrates. ... The endocrine (i. ... In cell biology, molecular biology and related fields, the word extracellular means outside the cell. It is used in contrast to intracellular (inside the cell). ... Covalent redirects here. ... Glycation is the result of a sugar-reducing molecule, such as fructose or glucose, bonding to a protein or lipid molecule without the controlling action of an enzyme. ... Peptidases (proteases [pronounced pro-tea-aces] and proteolytic enzymes are also commonly used) are enzymes which break peptide bonds of proteins. ... Cell signaling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. ... See diabetes mellitus for further general information on diabetes. ... Diabetes mellitus type 1 is a form of diabetes mellitus. ... Maturity onset diabetes of the young (MODY) refers to any of several rare hereditary forms of diabetes mellitus due to dominantly inherited defects of insulin secretion. ... G-Actin (PDB code: 1j6z). ... The eukaryotic cytoskeleton. ... Antagonists will block the binding of an agonist at a receptor molecule, inhibiting the signal produced by a receptor-agonist coupling. ... Glucagon ball and stick model A microscopic image stained for glucagon. ... This article is about the chemical family of steroids. ... This article is about the medical term. ... Hyperproinsulinemia is an autosomal dominant condition, results in approximately equal amounts of insulin and abnormally processed proinsulin being release into the circulation. ... For the disease characterized by excretion of large amounts of very dilute urine, see diabetes insipidus. ... Pharmacology (in Greek: pharmacon is drug, and logos is science) is the study of how chemical substances interfere with living systems. ... Novo Nordisks NovoLog® substituting a single amino acid Aventiss Lantus® substituting a single amino acid and adding two extra amino acids to the c-terminus of the b-chain Glargine versus NPH insulin in duration Through genetic engineering of the underlying DNA, the primary amino acid sequence of... Insulin aspart (marketed by Novo Nordisk as NovoLog) is a fast acting insulin analogue. ... Levemir (insulin detemir) is a basal insulin analogue created by Novo Nordisk. ... Lantus is long-acting insulin analogue, usually given once a day, to help control the blood sugar level of those with diabetes. ... The Entrez logo The Entrez Global Query Cross-Database Search System allows access to databases at the National Center for Biotechnology Information (NCBI) website. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... Swiss-Prot is a curated biological database of protein sequences created in 1986 by Amos Bairoch during his PhD and developed by the Swiss Institute of Bioinformatics and the European Bioinformatics Institute. ... National Center for Biotechnology Information logo The National Center for Biotechnology Information (NCBI) is part of the United States National Library of Medicine (NLM), a branch of the National Institutes of Health. ... For other uses, see Hormone (disambiguation). ... Drawing of the structure of cork as it appeared under the microscope to Robert Hooke from Micrographia which is the origin of the word cell being used to describe the smallest unit of a living organism Cells in culture, stained for keratin (red) and DNA (green) The cell is the... For the bird, see Liver bird. ... For other uses of Muscles, see Muscles (disambiguation). ... Glucose (Glc), a monosaccharide (or simple sugar), is an important carbohydrate in biology. ... This article does not cite any references or sources. ... Adipocytes are the cells that primarily compose adipose tissue, specialized in storing energy as fat. ... Some common lipids. ... Example of an unsaturated fat triglyceride. ... Anabolism is the metabolic process that builds larger molecules from smaller ones. ...


Insulin is used medically to treat some forms of diabetes mellitus. Patients with type 1 diabetes mellitus depend on external insulin (most commonly injected subcutaneously) for their survival because of the absence of the hormone. Patients with type 2 diabetes mellitus have insulin resistance, relatively low insulin production, or both; some type 2 diabetics eventually require insulin when other medications become insufficient in controlling blood glucose levels. For the disease characterized by excretion of large amounts of very dilute urine, see diabetes insipidus. ... Diabetes mellitus type 1 (Type 1 diabetes, Type I diabetes, T1D, IDDM) is a form of diabetes mellitus. ... An injection is a method of putting liquid into the body with a hollow needle and a syringe which is pierced through the skin to a sufficient depth for the material to be forced into the body. ... Diabetes mellitus type 2 or Type 2 Diabetes (formerly called non-insulin-dependent diabetes (NIDDM), obesity-related diabetes, or adult-onset diabetes) is a metabolic disorder that is primarily characterized by insulin resistance, relative insulin deficiency, and hyperglycemia. ... Insulin resistance is the condition in which normal amounts of insulin are inadequate to produce a normal insulin response from fat, muscle and liver cells. ...


Insulin is a peptide hormone composed of 51 amino acid residues and has a molecular weight of 5808 Da. It is produced in the Islets of Langerhans in the pancreas. The name comes from the Latin insula for "island". Peptide hormones are a class of peptides that are secreted into the blood stream and have endocrine functions in living animals. ... This article is about the class of chemicals. ... The molecular mass of a substance (less accurately called molecular weight and abbreviated as MW) is the mass of one molecule of that substance, relative to the unified atomic mass unit u (equal to 1/12 the mass of one atom of carbon-12). ... The unified atomic mass unit (u), or dalton (Da), is a small unit of mass used to express atomic masses and molecular masses. ... A porcine islet of Langerhans. ... The pancreas is a gland organ in the digestive and endocrine systems of vertebrates. ... For other uses, see Latin (disambiguation). ...


Insulin's genetic structure varies marginally between species of animal. Insulin from animal sources differs somewhat in regulatory function strength (i.e., in carbohydrate metabolism) in humans because of those variations. Porcine (pig) insulin is especially close to the human version. For other uses, see Species (disambiguation). ... The smooth endoplasmic reticulum is responsible for some carbohydrate metabolism. ... For other uses, see Pig (disambiguation). ... This article is about modern humans. ...

Contents

Discovery and characterization

In 1869 Paul Langerhans, a medical student in Berlin, was studying the structure of the pancreas (the jelly-like gland behind the stomach) under a microscope when he identified some previously un-noticed tissue clumps scattered throughout the bulk of the pancreas. The function of the "little heaps of cells," later known as the Islets of Langerhans, was unknown, but Edouard Laguesse later suggested that they might produce secretions that play a regulatory role in digestion. Paul Langerhans' son, Archibald, also helped to understand this regulatory role. Paul Langerhans (1847 - 1888) was a famous German pathologist and biologist. ... This article is about the capital of Germany. ... Robert Hookes microscope (1665) - an engineered device used to study living systems. ... An eponym is the name of a person, whether real or fictitious, who has (or is thought to have) given rise to the name of a particular place, tribe, discovery, or other item. ... A porcine islet of Langerhans. ... Gustave-Edouard Laguesse (1861-1927) was a French pathologist and histologist who was a native of Dijon. ...


In 1889, the Polish-German physician Oscar Minkowski in collaboration with Joseph von Mering removed the pancreas from a healthy dog to test its assumed role in digestion. Several days after the dog's pancreas was removed, Minkowski's animal keeper noticed a swarm of flies feeding on the dog's urine. On testing the urine they found that there was sugar in the dog's urine, establishing for the first time a relationship between the pancreas and diabetes. In 1901, another major step was taken by Eugene Opie, when he clearly established the link between the Islets of Langerhans and diabetes: Diabetes mellitus … is caused by destruction of the islets of Langerhans and occurs only when these bodies are in part or wholly destroyed. Before his work, the link between the pancreas and diabetes was clear, but not the specific role of the islets. “Deutschland” redirects here. ... Oskar Minkowski (January 13, 1858, Aleksotas near Kaunas, Lithuania - July 18, 1931, Mecklenburg, Germany) was the famous doctor. ... Joseph, Baron von Mering (born February 28, 1849, in Cologne - died January 5, 1908, at Halle an der Saale, Germany) was a German physician. ... The pancreas is a gland organ in the digestive and endocrine systems of vertebrates. ...

The structure of insulin. The left side is a space-filling model of the insulin monomer, believed to be biologically active. Carbon is green, hydrogen white, oxygen red, and nitrogen blue. On the right side is a cartoon of the insulin hexamer, believed to be the stored form. A monomer unit is highlighted with the A chain in blue and the B chain in cyan. Yellow denotes disulfide bonds, and magenta spheres are zinc ions.
The structure of insulin. The left side is a space-filling model of the insulin monomer, believed to be biologically active. Carbon is green, hydrogen white, oxygen red, and nitrogen blue. On the right side is a cartoon of the insulin hexamer, believed to be the stored form. A monomer unit is highlighted with the A chain in blue and the B chain in cyan. Yellow denotes disulfide bonds, and magenta spheres are zinc ions.

Over the next two decades, several attempts were made to isolate whatever it was the islets produced as a potential treatment. In 1906 George Ludwig Zuelzer was partially successful treating dogs with pancreatic extract but was unable to continue his work. Between 1911 and 1912, E.L. Scott at the University of Chicago used aqueous pancreatic extracts and noted a slight diminution of glycosuria but was unable to convince his director of his work's value; it was shut down. Israel Kleiner demonstrated similar effects at Rockefeller University in 1919, but his work was interrupted by World War I and he did not return to it. Nicolae Paulescu, a professor of physiology at the University of Medicine and Pharmacy in Bucharest was the first one to isolate insulin, which he called at that time pancrein, and published his work in 1921 that had been carried out in Bucharest. Use of his techniques was patented in Romania, though no clinical use resulted.[1] Image File history File links Download high resolution version (1417x1063, 197 KB) Summary Created by Isaac Yonemoto. ... Image File history File links Download high resolution version (1417x1063, 197 KB) Summary Created by Isaac Yonemoto. ... For other uses, see Carbon (disambiguation). ... This article is about the chemistry of hydrogen. ... General Name, symbol, number oxygen, O, 8 Chemical series nonmetals, chalcogens Group, period, block 16, 2, p Appearance colorless (gas) pale blue (liquid) Standard atomic weight 15. ... General Name, symbol, number nitrogen, N, 7 Chemical series nonmetals Group, period, block 15, 2, p Appearance colorless gas Standard atomic weight 14. ... George Ludwig Zuelzer (German spelling- Georg Ludwig Zülzer) (April 10, 1870 - October 16, 1949) was a German physician who was a native of Berlin. ... For other uses, see University of Chicago (disambiguation). ... Founders Hall Rockefeller University is a private university focusing primarily on graduate and postgraduate education research in the biomedical fields, located between 63rd and 68th Streets along York Avenue, on the Upper East Side of Manhattan island in New York City, New York. ... “The Great War ” redirects here. ... Nicolae Paulescu (October 30, 1869, Bucharest - July 17, 1931, Bucharest) was a Romanian physiologist, professor of medicine and the discoverer of insulin. ...


In October 1920, Frederick Banting was reading one of Minkowski's papers and concluded that it is the very digestive secretions that Minkowski had originally studied that were breaking down the islet secretion(s), thereby making it impossible to extract successfully. He jotted a note to himself Ligate pancreatic ducts of the dog. Keep dogs alive till acini degenerate leaving islets. Try to isolate internal secretion of these and relieve glycosurea. Sir Frederick Grant Banting, KBE, MC, MD, FRSC (November 14, 1891 – February 21, 1941) was a Canadian medical scientist, doctor and Nobel laureate noted as one of the co-discovers of insulin. ...


The idea was that the pancreas's internal secretion, which supposedly regulates sugar in the bloodstream, might hold the key to the treatment of diabetes.


He travelled to Toronto, ON to meet with J.J.R. Macleod, who was not entirely impressed with his idea – so many before him had tried and failed. Nevertheless, he supplied Banting with a lab at the University of Toronto, an assistant (medical student Charles Best), and 10 dogs, then left on vacation during the summer of 1921.[when? ] Their method was tying a ligature (string) around the pancreatic duct, and, when examined several weeks later, the pancreatic digestive cells had died and been absorbed by the immune system, leaving thousands of islets. They then isolated an extract from these islets, producing what they called isletin (what we now know as insulin), and tested this extract on the dogs. Banting and Best were then able to keep a pancreatectomized dog alive all summer[when? ] because the extract lowered the level of sugar in the blood. ... John James Richard Macleod John James Richard Macleod (September 6, 1876 – March 16, 1935) was a Scottish physician, physiologist, and recipient of the Nobel Prize in Physiology or Medicine. ... The University of Toronto (U of T) is a public research university in the city of Toronto, Ontario, Canada. ... Charles Herbert Best, CC, (February 27, 1899 – March 31, 1978) was a medical scientist. ...

Computer-generated image of insulin hexamers highlighting the threefold symmetry, the zinc ions holding it together, and the histidine residues involved in zinc binding.
Computer-generated image of insulin hexamers highlighting the threefold symmetry, the zinc ions holding it together, and the histidine residues involved in zinc binding.

Macleod saw the value of the research on his return but demanded a re-run to prove the method actually worked. Several weeks later it was clear the second run was also a success, and he helped publish their results privately in Toronto, ON that November. However, they needed six weeks to extract the isletin, which forced considerable delays. Banting suggested that they try to use fetal calf pancreas, which had not yet developed digestive glands; he was relieved to find that this method worked well. With the supply problem solved, the next major effort was to purify the extract. In December 1921, Macleod invited the biochemist James Collip to help with this task, and, within a month, the team felt ready for a clinical test. Image File history File links InsulinHexamer. ... Image File history File links InsulinHexamer. ... Sphere symmetry group o. ... General Name, symbol, number zinc, Zn, 30 Chemical series transition metals Group, period, block 12, 4, d Appearance bluish pale gray Standard atomic weight 65. ... Histidine is one of the 20 most common natural amino acids present in proteins. ... ... A biochemist is a scientist trained and dedicated to producing results in the discipline of biochemistry. ... James Collip was part of the Toronto group which helped create insulin. ...


On January 11, 1922, Leonard Thompson, a 14-year-old diabetic who lay dying at the Toronto General Hospital, was given the first injection of insulin. However, the extract was so impure that Thompson suffered a severe allergic reaction, and further injections were canceled. Over the next 12 days, Collip worked day and night to improve the ox-pancreas extract, and a second dose injected on the 23rd. This was completely successful, not only in not having obvious side-effects, but in completely eliminating the glycosuria sign of diabetes. is the 11th day of the year in the Gregorian calendar. ... Year 1922 (MCMXXII) was a common year starting on Sunday (link will display full calendar) of the Gregorian calendar. ... Leonard Thompson is regarded as the very first person to have received injection of insulin as a treatment for diabetes. ... The R.R. McEwen atrium of the Toronto General Hospital, southwest corner of the site, view from University Avenue. ... Anaphylaxis is an acute systemic (multi-system) and severe Type I Hypersensitivity allergic reaction in humans and other mammals. ...


Children dying from diabetic keto-acidosis were kept in large wards, often with 50 or more patients in a ward, mostly comatose. Grieving family members were often in attendance, awaiting the (until then, inevitable) death. In one of medicine's more dramatic moments Banting, Best and Collip went from bed to bed, injecting an entire ward with the new purified extract. Before they had reached the last dying child, the first few were awakening from their coma, to the joyous exclamations of their families.


However, Banting and Best never worked well with Collip, regarding him as something of an interloper, and Collip left the project soon after.


Over the spring of 1922,[when? ] Best managed to improve his techniques to the point where large quantities of insulin could be extracted on demand, but the preparation remained impure. The drug firm Eli Lilly and Company had offered assistance not long after the first publications in 1921, and they took Lilly up on the offer in April. In November, Lilly made a major breakthrough, and were able to produce large quantities of purer insulin. Insulin was offered for sale shortly thereafter. Eli Lilly and Company (NYSE: LLY) is a global pharmaceutical company and one of the worlds largest corporations. ...


Nobel Prizes

The Nobel Prize committee in 1923 credited the practical extraction of insulin to a team at the University of Toronto and awarded the Nobel Prize to two men; Frederick Banting and J.J.R. Macleod. They were awarded the Nobel Prize in Physiology or Medicine in 1923 for the discovery of insulin. Banting, insulted that Best was not mentioned, shared his prize with Best, and Macleod immediately shared his with Collip. The patent for insulin was sold to the University of Toronto for one dollar. The University of Toronto (U of T) is a public research university in the city of Toronto, Ontario, Canada. ... Sir Frederick Grant Banting, KBE, MC, MD, FRSC (November 14, 1891 – February 21, 1941) was a Canadian medical scientist, doctor and Nobel laureate noted as one of the co-discovers of insulin. ... Emil Adolf von Behring was the first person to receive the Nobel Prize in Physiology or Medicine, for his work on the treatment of diphtheria. ... Year 1923 (MCMXXIII) was a common year starting on Monday (link will display the full calendar) of the Gregorian calendar. ... The University of Toronto (U of T) is a public research university in the city of Toronto, Ontario, Canada. ...


The primary structure of insulin was determined by British molecular biologist Frederick Sanger. It was the first protein to have its sequence be determined. He was awarded the 1958 Nobel Prize in Chemistry for this work. A protein primary structure is a chain of amino acids. ... Frederick Sanger, OM, CH, CBE, FRS (born 13 August 1918) is an English biochemist and a two time Nobel laureate in chemistry. ... Jan. ... This is a list of Nobel Prize laureates in Chemistry from 1901 to 2006. ...


In 1969, after decades of work, Dorothy Crowfoot Hodgkin determined the spatial conformation of the molecule, the so-called tertiary structure, by means of X-ray diffraction studies. She had been awarded a Nobel Prize in Chemistry in 1964 for the development of crystallography. Dorothy Mary Crowfoot Hodgkin, OM , FRS (12 May 1910 – 29 July 1994) was a British founder of protein crystallography. ... In biochemistry and chemistry, the tertiary structure of a protein or any other macromolecule is its three-dimensional structure, as defined by the atomic coordinates. ... X-ray crystallography is a technique in crystallography in which the pattern produced by the diffraction of x-rays through the closely spaced lattice of atoms in a crystal is recorded and then analyzed to reveal the nature of that lattice. ... This is a list of Nobel Prize laureates in Chemistry from 1901 to 2006. ... Also Nintendo emulator: 1964 (emulator). ... Crystallography (from the Greek words crystallon = cold drop / frozen drop, with its meaning extending to all solids with some degree of transparency, and graphein = write) is the experimental science of determining the arrangement of atoms in solids. ...


Rosalyn Sussman Yalow received the 1977 Nobel Prize in Medicine for the development of the radioimmunoassay for insulin. Rosalyn Sussman Yalow (born on July 19, 1921) is an American medical physicist, and a co-winner of the 1977 Nobel Prize in Physiology or Medicine for her development of the radioimmunoassay (RIA) technique. ... Also: 1977 (album) by Ash. ... List of Nobel Prize laureates in Physiology or Medicine from 1901 to the present day. ... Radioimmunoassay is a scientific method used to test hormone levels in the blood without the need to use a bioassay. ...


Structure and production

Insulin undergoes extensive posttranslational modification along the production pathway. Production and secretion are largely independent; prepared insulin is stored awaiting secretion. Both C-peptide and mature insulin are biologically active. Cell components and proteins in this image are not to scale.
Insulin undergoes extensive posttranslational modification along the production pathway. Production and secretion are largely independent; prepared insulin is stored awaiting secretion. Both C-peptide and mature insulin are biologically active. Cell components and proteins in this image are not to scale.

Within vertebrates, the similarity of insulins is very close. Bovine insulin differs from human in only three amino acid residues, and porcine insulin in one. Even insulin from some species of fish is similar enough to human to be effective in humans. The C-peptide of proinsulin (discussed later), however, is very divergent from species to species. Image File history File links Download high resolution version (1488x2105, 524 KB) Summary created by Isaac Yonemoto using Inkscape Licensing This image is licensed under the Creative Commons Attribution License v. ... Image File history File links Download high resolution version (1488x2105, 524 KB) Summary created by Isaac Yonemoto using Inkscape Licensing This image is licensed under the Creative Commons Attribution License v. ... COW is an acronym for a number of things: Can of worms The COW programming language, an esoteric programming language. ... This article is about the class of chemicals. ... For other uses, see Pig (disambiguation). ...


In mammals, insulin is synthesized in the pancreas within the beta cells (β-cells) of the islets of Langerhans. One to three million islets of Langerhans (pancreatic islets) form the endocrine part of the pancreas, which is primarily an exocrine gland. The endocrine portion only accounts for 2% of the total mass of the pancreas. Within the islets of Langerhans, beta cells constitute 60–80% of all the cells. The pancreas is a gland organ in the digestive and endocrine systems of vertebrates. ... Beta cells are a type of cell in the pancreas in areas called the islets of Langerhans. ... A porcine islet of Langerhans. ... The endocrine system is a control system of ductless endocrine glands that secrete chemical messengers called hormones that circulate within the body via the bloodstream to affect distant organs. ... Exocrine gland refers to glands that secrete their products via a duct. ... Human submaxillary gland. ...


In beta cells, insulin is synthesized from the proinsulin precursor molecule by the action of proteolytic enzymes, known as prohormone convertases (PC1 and PC2), as well as the exoprotease carboxypeptidase E. These modifications of proinsulin remove the center portion of the molecule, or C-peptide, from the C- and N- terminal ends of the proinsulin. The remaining polypeptides (51 amino acids in total), the B- and A- chains, are bound together by disulfide bonds/disulphide bonds. Confusingly, the primary sequence of proinsulin goes in the order "B-C-A", since B and A chains were identified on the basis of mass, and the C peptide was discovered after the others. Carboxypeptidase is an enzyme that hydrolyzes the first peptide or amide bond at the carboxyl or C-terminal end of proteins and peptides. ... C-peptide is a peptide which is made when proinsulin is split into insulin and C-peptide. ... In chemistry, a disulfide bond is a single covalent bond derived from the coupling of thiol groups. ...


Actions on cellular and metabolic level

Effect of insulin on glucose uptake and metabolism. Insulin binds to its receptor (1) which in turn starts many protein activation cascades (2). These include: translocation of Glut-4 transporter to the plasma membrane and influx of glucose (3), glycogen synthesis (4), glycolysis (5) and fatty acid synthesis (6).
Effect of insulin on glucose uptake and metabolism. Insulin binds to its receptor (1) which in turn starts many protein activation cascades (2). These include: translocation of Glut-4 transporter to the plasma membrane and influx of glucose (3), glycogen synthesis (4), glycolysis (5) and fatty acid synthesis (6).

The actions of insulin on the global human metabolism level include: Image File history File links Download high resolution version (1291x754, 72 KB) Summary author: meiquer, 1291x754x16M jpeg 76400 bytes created: June 06, 2006 Licensing I, the creator of this work, hereby grant the permission to copy, distribute and/or modify this document under the terms of the GNU Free Documentation... Image File history File links Download high resolution version (1291x754, 72 KB) Summary author: meiquer, 1291x754x16M jpeg 76400 bytes created: June 06, 2006 Licensing I, the creator of this work, hereby grant the permission to copy, distribute and/or modify this document under the terms of the GNU Free Documentation... Drawing of a cell membrane A component of every biological cell, the cell membrane (or plasma membrane) is a thin and structured bilayer of phospholipid and protein molecules that envelopes the cell. ... This article does not cite any references or sources. ... The word glycolysis is derived from Greek γλυκύς (sweet) and λύσις (letting loose). ... In chemistry, especially biochemistry, a fatty acid is a carboxylic acid often with a long unbranched aliphatic tail (chain), which is either saturated or unsaturated. ...

The actions of insulin on cells include: Glucose (Glc), a monosaccharide (or simple sugar), is an important carbohydrate in biology. ... DNA replication. ... Protein synthesis is the creation of proteins using DNA and RNA. Biological and artificial methods for creation of proteins differ significantly. ... Neuraminidase ribbon diagram An enzyme (in Greek en = in and zyme = blend) is a protein, or protein complex, that catalyzes a chemical reaction and also controls the 3D orientation of the catalyzed substrates. ... In biochemistry, an enzyme or other protein is allosteric if its activity or efficiency changes in response to the binding of an effector molecule at a so-called allosteric site. ...

  • Increased glycogen synthesis – insulin forces storage of glucose in liver (and muscle) cells in the form of glycogen; lowered levels of insulin cause liver cells to convert glycogen to glucose and excrete it into the blood. This is the clinical action of insulin which is directly useful in reducing high blood glucose levels as in diabetes.
  • Increased fatty acid synthesis – insulin forces fat cells to take in blood lipids which are converted to triglycerides; lack of insulin causes the reverse.
  • Increased esterification of fatty acids – forces adipose tissue to make fats (i.e., triglycerides) from fatty acid esters; lack of insulin causes the reverse.
  • Decreased proteinolysis – forces reduction of protein degradation; lack of insulin increases protein degradation.
  • Decreased lipolysis – forces reduction in conversion of fat cell lipid stores into blood fatty acids; lack of insulin causes the reverse.
  • Decreased gluconeogenesis – decreases production of glucose from non-sugar substrates, primarily in the liver (remember, the vast majority of endogenous insulin arriving at the liver never leaves the liver) ; lack of insulin causes glucose production from assorted substrates in the liver and elsewhere.
  • Increased amino acid uptake – forces cells to absorb circulating amino acids; lack of insulin inhibits absorption.
  • Increased potassium uptake – forces cells to absorb serum potassium; lack of insulin inhibits absorption.
  • Arterial muscle tone – forces arterial wall muscle to relax, increasing blood flow, especially in micro arteries; lack of insulin reduces flow by allowing these muscles to contract.

This article does not cite any references or sources. ... In chemistry, especially biochemistry, a fatty acid is a carboxylic acid often with a long unbranched aliphatic tail (chain), which is either saturated or unsaturated. ... Triglyceride (blue: fatty acid; red: glycerol backbone) Triglycerides are glycerides in which the glycerol is esterified with three fatty acids. ... Esterification is the general name for a chemical reaction in which two chemicals (typically an alcohol and an acid) form an ester as the reaction product. ... Adipose tissue is one of the main types of connective tissue. ... We dont have an article called Proteinolysis Start this article Search for Proteinolysis in. ... Lipolysis is the breakdown of fat stored in fat cells. ... Pyruvic acid Oxaloacetic acid Phosphoenolpyruvate Fructose 1,6-bisphosphate Fructose 6-phosphate Glucose-6-phosphate Glucose Gluconeogenesis is the generation of glucose from non-sugar carbon substrates like pyruvate, lactate, glycerol, and amino acids (primarily alanine and glutamine). ...

Regulatory action on blood glucose

Despite long intervals between meals or the occasional consumption of meals with a substantial carbohydrate load, human blood glucose levels normally remain within a remarkably narrow range. In most humans this varies from about 70 mg/dl to perhaps 110 mg/dl (3.9 to 6.1 mmol/litre) except shortly after eating when the blood glucose level rises temporarily. This homeostatic effect is the result of many factors, of which hormone regulation is the most important. Lactose is a disaccharide found in milk. ... In medicine, blood sugar is glucose in the blood. ... The mole (symbol: mol) is one of the seven SI base units and is commonly used in chemistry. ... Homeostasis is the property of either an open system or a closed system, especially a living organism, which regulates its internal environment so as to maintain a stable, constant condition. ...


It is usually a surprise to realize how little glucose is actually maintained in the blood and body fluids. The control mechanism works on very small quantities. In a healthy adult male of 75 kg with a blood volume of 5 litres, a blood glucose level of 100 mg/dl or 5.5 mmol/l corresponds to about 5 g (1/5 ounce) of glucose in the blood and approximately 45 g (1½ ounces) in the total body water (which obviously includes more than merely blood and will be usually about 60% of the total body weight in men). A more familiar comparison may help – 5 grams of glucose is about equivalent to a commercial sugar packet (as provided in many restaurants with coffee or tea). “Kg” redirects here. ... Human blood smear: a - erythrocytes; b - neutrophil; c - eosinophil; d - lymphocyte. ... The litre or liter (see spelling differences) is a unit of volume. ... A significant fraction of the human body is water. ... It has been suggested that this article or section be merged with human weight. ... For other uses, see Coffee (disambiguation). ... For other uses, see Tea (disambiguation). ...


There are two types of mutually antagonistic metabolic hormones affecting blood glucose levels:

Mechanisms which restore satisfactory blood glucose levels after hypoglycemia must be quick and effective, because of the immediate serious consequences of insufficient glucose (in the extreme, coma, less immediately dangerously, confusion or unsteadiness, amongst many other effects). This is because, at least in the short term, it is far more dangerous to have too little glucose in the blood than too much. In healthy individuals these mechanisms are indeed generally efficient, and symptomatic hypoglycemia is generally only found in diabetics using insulin or other pharmacologic treatment. Such hypoglycemic episodes vary greatly between persons and from time to time, both in severity and swiftness of onset. In severe cases prompt medical assistance is essential, as damage (to brain and other tissues) and even death will result from sufficiently low blood glucose levels. Glucagon ball and stick model A microscopic image stained for glucagon. ... Growth hormone (GH) or somatotropin (STH) is a protein hormone which stimulates growth and cell reproduction in humans and other animals. ... Catecholamines are chemical compounds derived from the amino acid tyrosine that act as hormones or neurotransmitters. ... Hypoglycemia (hypoglycaemia in British English) is a medical term referring to a pathologic state produced by a lower than normal level of glucose (sugar) in the blood. ...


Beta cells in the islets of Langerhans are sensitive to variations in blood glucose levels through the following mechanism (see figure to the right):

  • Glucose enters the beta cells through the glucose transporter GLUT2
  • Glucose goes into the glycolysis and the respiratory cycle where multiple high-energy ATP molecules are produced by oxidation
  • Dependent on ATP levels, and hence blood glucose levels, the ATP-controlled potassium channels (K+) close and the cell membrane depolarizes
  • On depolarisation, voltage controlled calcium channels (Ca2+) open and calcium flows into the cells
  • An increased calcium level causes activation of phospholipase C, which cleaves the membrane phospholipid phosphatidyl inositol 4,5-bisphosphate into inositol 1,4,5-triphosphate and diacylglycerol.
  • Inositol 1,4,5-triphosphate (IP3) binds to receptor proteins in the membrane of endoplasmic reticulum (ER). This allows the release of Ca2+ from the ER via IP3 gated channels, and further raises the cell concentration of calcium.
  • Significantly increased amounts of calcium in the cells causes release of previously synthesised insulin, which has been stored in secretory vesicles

This is the main mechanism for release of insulin and regulation of insulin synthesis. In addition some insulin synthesis and release takes place generally at food intake, not just glucose or carbohydrate intake, and the beta cells are also somewhat influenced by the autonomic nervous system. The signalling mechanisms controlling this are not fully understood. Beta cells are a type of cell in the pancreas in areas called the islets of Langerhans. ... To meet Wikipedias quality standards, this article or section may require cleanup. ... GLUT 2 is a transmembrane protein which is involved in passive transport of glucose over cellular membranes of Liver, beta cells, hypothalamus, basolateral membrane small intestine. ... The word glycolysis is derived from Greek γλυκύς (sweet) and λύσις (letting loose). ... Adenosine 5-triphosphate (ATP) is a multifunctional nucleotide that is most important as a molecular currency of intracellular energy transfer. ... In cell biology, potassium channels are the most common type of ion channel. ... In neuroscience, depolarization refers to the event a neuron undergoes when its membrane potential grows more positive with respect to the extracellular solution. ... Another, unrelated ion channeling process is part of ion implantation. ... A phospholipase is an enzyme that converts phospholipids into fatty acids and other lipophilic substances. ... Chemical structure of sn-1-stearoyl-2-arachidonoyl phosphatidylinositol 4,5-bisphosphate Phosphatidylinositol (4,5)-bisphosphate (PtdIns(4,5)P2) is a minor phospholipid component of cell membranes. ... Inositol triphosphate or inositol 1,4,5-triphosphate (also commonly known as inositol trisphosphate or triphosphoinositol; abbreviated InsP3 or IP3), together with diacylglycerol, is a second messenger molecule used in signal transduction in biological cells. ... OWNEDOWNEDOWNED ... The endoplasmic reticulum or ER is an organelle found in all eukaryotic cells that is an interconnected network of tubules, vesicles and cisternae that is responsible for several specialized functions: Protein translation, folding, and transport of proteins to be used in the cell membrane (e. ... Secretion is the process of segregating, elaborating, and releasing chemicals from a cell, or a secreted chemical substance or amount of substance. ... In cell biology, a vesicle is a relatively small and enclosed compartment, separated from the cytosol by at least one lipid bilayer. ... Lactose is a disaccharide found in milk. ... This article or section is in need of attention from an expert on the subject. ...


Other substances known which stimulate insulin release are acetylcholine, released from vagus nerve endings (parasympathetic nervous system), cholecystokinin, released by enteroendocrine cells of intestinal mucosa and glucose-dependent insulinotropic peptide (GIP). The first of these acts similarly to glucose through phospholipase C, while the last acts through the mechanism of adenylate cyclase. Autonomic nervous system innervation, showing the sympathetic and parasympathetic (craniosacral) systems, in red and blue, respectively The parasympathetic nervous system is one of three divisions of the autonomic nervous system. ... Cholecystokinin (from Greek chole, bile; cysto, sac; kinin, move; hence, move the bile-sac (gall bladder)) is a peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat and protein. ... Enteroendocrine cells are specialized endocrine cells of the gastrointestinal tract. ... For the Physics term GUT, please refer to Grand unification theory The gastrointestinal or digestive tract, also referred to as the GI tract or the alimentary canal or the gut, is the system of organs within multicellular animals which takes in food, digests it to extract energy and nutrients, and... Glucose-dependent insulinotropic peptide (GIP) is a member of the secretin family of hormones. ... Epinephrine binds its receptor, that associates with an heterotrimeric G protein. ...


The sympathetic nervous system (via α2-adrenergic agonists such as clonidine) inhibits the release of insulin. The Sympathetic Nervous System (SNS) is a branch of the autonomic nervous system. ... The adrenergic receptors (or adrenoceptors) are a class of G protein-coupled receptors that are targets of the catecholamines. ... Clonidine is a direct-acting adrenergic agonist prescribed historically as an anti-hypertensive agent. ...


When the glucose level comes down to the usual physiologic value, insulin release from the beta cells slows or stops. If blood glucose levels drop lower than this, especially to dangerously low levels, release of hyperglycemic hormones (most prominently glucagon from Islet of Langerhans' alpha cells) forces release of glucose into the blood from cellular stores, primarily liver cell stores of glycogen. By increasing blood glucose, the hyperglycemic hormones correct life-threatening hypoglycemia. Release of insulin is strongly inhibited by the stress hormone norepinephrine (noradrenaline), which leads to increased blood glucose levels during stress. Stress hormones such as cortisol and norepinephrine are released at periods of high stress. ... Norepinephrine (INN)(abbr. ...


Signal transduction

There are special transporter proteins in cell membranes through which glucose from the blood can enter a cell. These transporters are, indirectly, under insulin control in certain body cell types (e.g., muscle cells). Low levels of circulating insulin, or its absence, will prevent glucose from entering those cells (e.g., in untreated Type 1 diabetes). However, more commonly there is a decrease in the sensitivity of cells to insulin (e.g., the reduced insulin sensitivity characteristic of Type 2 diabetes), resulting in decreased glucose absorption. In either case, there is 'cell starvation', weight loss, sometimes extreme. In a few cases, there is a defect in the release of insulin from the pancreas. Either way, the effect is, characteristically, the same: elevated blood glucose levels. Look up cell membrane in Wiktionary, the free dictionary. ... Glucose (Glc), a monosaccharide (or simple sugar), is an important carbohydrate in biology. ...


Activation of insulin receptors leads to internal cellular mechanisms that directly affect glucose uptake by regulating the number and operation of protein molecules in the cell membrane that transport glucose into the cell. The genes that specify the proteins that make up the insulin receptor in cell membranes have been identified and the structure of the interior, cell membrane section, and now, finally after more than a decade, the extra-membrane structure of receptor (Australian researchers announced the work 2Q 2006). In molecular biology, the insulin receptor is a transmembrane receptor that is activated by insulin. ...


Two types of tissues are most strongly influenced by insulin, as far as the stimulation of glucose uptake is concerned: muscle cells (myocytes) and fat cells (adipocytes). The former are important because of their central role in movement, breathing, circulation, etc, and the latter because they accumulate excess food energy against future needs. Together, they account for about two-thirds of all cells in a typical human body. Myocyte is the technical term for a muscle cell. ... Adipocytes are the cells that primarily compose adipose tissue, specialized in storing energy as fat. ... Food energy is the amount of energy in food that is available through digestion. ...


Insulin degradation

Once an insulin molecule has docked onto the receptor and effected its action, it may be released back into the extracellular environment or it may be degraded by the cell. Degradation normally involves endocytosis of the insulin-receptor complex followed by the action of insulin degrading enzyme. Most insulin molecules are degraded by liver cells. It has been estimated that a typical insulin molecule that is produced endogenously by the pancreatic beta cells is finally degraded about 71 minutes after its initial release into circulation.[2] Endocytosis (IPA: ) is a process whereby cells absorb material (molecules such as proteins) from the outside by engulfing it with their cell membrane. ... Insulin Degrading Enzyme (IDE) is a large zinc-binding protease of the M16A metalloprotease subfamily known to cleave multiple short polypeptides that vary considerably in sequence. ... For the bird, see Liver bird. ...


Hypoglycemia

Although other cells can use other fuels for a while (most prominently fatty acids), neurons depend on glucose as a source of energy in the non-starving human. They do not require insulin to absorb glucose, unlike muscle and adipose tissue, and they have very small internal stores of glycogen. Glycogen stored in liver cells (unlike glycogen stored in muscle cells) can be converted to glucose, and released into the blood, when glucose from digestion is low or absent, and the glycerol backbone in triglycerides can also be used to produce blood glucose. Neurons (also called nerve cells) are the primary cells of the nervous system. ... Glycerine, Glycerin redirects here. ... Triglyceride (blue: fatty acid; red: glycerol backbone) Triglycerides are glycerides in which the glycerol is esterified with three fatty acids. ...


Exhaustion of these sources can, either temporarily or on a sustained basis, if reducing blood glucose to a sufficiently low level, first and most dramatically manifest itself in impaired functioning of the central nervous system – dizziness, speech problems, even loss of consciousness, are not unknown. This is known as hypoglycemia or, in cases producing unconsciousness, "hypoglycemic coma" (formerly termed "insulin shock" from the most common causative agent). Endogenous causes of insulin excess (such as an insulinoma) are very rare, and the overwhelming majority of hypoglycemia cases are caused by human action (e.g., iatrogenic, caused by medicine) and are usually accidental. There have been a few reported cases of murder, attempted murder, or suicide using insulin overdoses, but most insulin shocks appear to be due to errors in dosage of insulin (e.g., 20 units of insulin instead of 2) or other unanticipated factors (didn't eat as much as anticipated, or exercised more than expected). A diagram showing the CNS: 1. ... Hypoglycemia (hypoglycaemia in British English) is a medical term referring to a pathologic state produced by a lower than normal level of glucose (sugar) in the blood. ... An insulinoma is a tumour of the pancreas derived from the beta cells which while retaining the ability to synthesize and secrete insulin is autonomous of the normal feedback mechanisms. ... An iatrogenic (pronounced , IPA) condition is a state of ill health or adverse effect caused by medical treatment, usually due to mistakes made in treatment. ...


Possible causes of hypoglycemia include:

  • External insulin (usually injected subcutaneously).
  • Oral hypoglycemic agents (e.g., any of the sulfonylureas, or similar drugs, which increase insulin release from beta cells in response to a particular blood glucose level).
  • Ingestion of low-carbohydrate sugar substitutes (animal studies show these can trigger insulin release (albeit in much smaller quantities than sugar) according to a report in Discover magazine, August 2005, p18).

Diseases and syndromes

There are several conditions in which insulin disturbance is pathologic:

  • Diabetes mellitus – general term referring to all states characterized by hyperglycemia.
    • Type 1 – autoimmune-mediated destruction of insulin producing beta cells in the pancreas resulting in absolute insulin deficiency.
    • Type 2 – multifactoral syndrome with combined influence of genetic susceptibility and influence of environmental factors, the best known being obesity, age, and physical inactivity, resulting in insulin resistance in cells requiring insulin for glucose absorption. This form of diabetes is strongly inherited.
    • Other types of impaired glucose tolerance (see the diabetes article).
  • Insulinoma or reactive hypoglycemia.
  • Metabolic syndrome – a poorly understood condition first called Syndrome X by Gerald Reaven, Reaven's Syndrome after Reaven, CHAOS in Australia (from the signs which seem to travel together), and sometimes prediabetes. It is currently not clear whether these signs have a single, treatable cause, or are the result of body changes leading to type 2 diabetes. It is characterized by elevated blood pressure, dyslipidemia (disturbances in blood cholesterol forms and other blood lipids), and increased waist circumference (at least in populations in much of the developed world). The basic underlying cause may be the insulin resistance of type 2 diabetes which is a diminished capacity for insulin response in some tissues (e.g., muscle, fat) to respond to insulin. Commonly, morbidities such as essential hypertension, obesity, Type 2 diabetes, and cardiovascular disease (CVD) develop.
  • Polycystic ovary syndrome – a complex syndrome in women in the reproductive years where there is anovulation and androgen excess commonly displayed as hirsutism. In many cases of PCOS insulin resistance is present.

For the disease characterized by excretion of large amounts of very dilute urine, see diabetes insipidus. ... For the disease characterized by excretion of large amounts of very dilute urine, see diabetes insipidus. ... For the disease characterized by excretion of large amounts of very dilute urine, see diabetes insipidus. ... Insulin resistance is the condition in which normal amounts of insulin are inadequate to produce a normal insulin response from fat, muscle and liver cells. ... This article is about the disease that features high blood sugar. ... An insulinoma is a tumour of the pancreas derived from the beta cells which while retaining the ability to synthesize and secrete insulin is autonomous of the normal feedback mechanisms. ... Reactive hypoglycemia is a medical term describing recurrent episodes of symptomatic hypoglycemia occurring 2-4 hours after a high carbohydrate meal (or oral glucose load). ... Metabolic syndrome is a combination of medical disorders that increase ones risk for cardiovascular disease and diabetes. ... (Cardiac) syndrome X is angina(Chest Pain) with signs associated with decreased blood flow to heart tissue but with normal Coronary arteries. ... Gerald Reaven is an American endocrinologist and professor emeritus in medicine at the Stanford University School of Medicine in Stanford, California. ... Prediabetes is a condition that almost always happens before diabetes. ... For other forms of hypertension, see Hypertension (disambiguation). ... Cardiovascular disease refers to the class of diseases that involve the heart or blood vessels (arteries and veins). ... Polycystic ovary syndrome (PCOS, also known clinically as Stein-Leventhal syndrome), is an endocrine disorder that affects approximately one in ten women. ... In medicine, anovulation is absence of ovulation when it would be normally expected (in a post-menarchal, premenopausal woman). ... Androgen is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of masculine characteristics in vertebrates by binding to androgen receptors. ... Hirsutism (from Latin hirsutus = shaggy, hairy) is defined as excessive and increased hair growth in women in locations where the occurrence of terminal hair normally is minimal or absent. ... Insulin resistance is the condition in which normal amounts of insulin are inadequate to produce a normal insulin response from fat, muscle and liver cells. ...

As a medication

Principles

Insulin is required for all animal life (not insects). Its mechanism of action is almost identical in nematode worms (e.g. C. elegans), fish, and mammals, and it is a protein that has been highly conserved across evolutionary time. In humans, insulin deprivation due to the removal or destruction of the pancreas leads to death in days or, at most, weeks. Insulin must be administered to patients who experience such a deprivation. Clinically, this condition is called diabetes mellitus type 1. Binomial name Caenorhabditis elegans Wild-type C. elegans hermaphrodite stained to highlight the nuclei of all cells Caenorhabditis elegans () is a free-living nematode (a roundworm), about 1 mm in length, which lives in a temperate soil environment. ... For the disease characterized by excretion of large amounts of very dilute urine, see diabetes insipidus. ...


The initial sources of insulin for clinical use in humans were cow, horse, pig or fish pancreases. Insulin from these sources is effective in humans as it is nearly identical to human insulin (three amino acid difference in bovine insulin, one amino acid difference in porcine). Differences in suitability of beef, pork, or fish derived insulin for individual patients have been primarily due to low preparation purity resulting in allergic reactions to the presence of non-insulin substances. Though purity has improved steadily since the 1920s, less severe allergic reactions still occur occasionally. Insulin production from animal pancreases was widespread for decades, but very few patients today rely on insulin from animal sources, largely because few pharmaceutical companies sell it anymore. COW is an acronym for a number of things: Can of worms The COW programming language, an esoteric programming language. ... Binomial name Equus caballus Linnaeus, 1758 The horse (Equus caballus, sometimes seen as a subspecies of the Wild Horse, Equus ferus caballus) is a large odd-toed ungulate mammal, one of ten modern species of the genus Equus. ... For other uses, see Pig (disambiguation). ... For other uses, see Fish (disambiguation). ...


Synthetic "human" insulin is now manufactured for widespread clinical use using genetic engineering techniques, which significantly reduces the presence of impurities. Eli Lilly marketed the first such insulin, Humulin, in 1982. Humulin was the first medication produced using modern genetic engineering techniques in which actual human DNA is inserted into a host cell (E. coli in this case). The host cells are then allowed to grow and reproduce normally, and due to the inserted human DNA, they produce a synthetic version of human insulin. Kenyans examining insect-resistant transgenic Bt corn. ... Eli Lilly and Company (NYSE: LLY) is a global pharmaceutical company and one of the worlds largest corporations. ... Year 1982 (MCMLXXXII) was a common year starting on Friday (link displays the 1982 Gregorian calendar). ...


Genentech developed the technique Lilly used to produce Humulin. Novo Nordisk has also developed a genetically engineered insulin independently. Most insulins used clinically today are produced this way, as they are usually less likely to produce an allergic reaction, although clinical evidence has provided only mixed evidence of this claim. Genentech, Inc. ... Novo Nordisk (OMX: NOVO B, NYSE: NVO) manufactures and markets pharmaceutical products and services. ...


Since January 2006, all insulins distributed in the U.S. and some other countries are synthetic "human" insulins or their analogs. A special FDA importation process is required to obtain bovine or porcine derived insulin for use in the U.S., though there may be some remaining stocks of porcine insulin made by Lilly in 2005 or earlier.


There are several problems with insulin as a clinical treatment for diabetes:

  • Mode of administration.
  • Selecting the 'right' dose and timing.
  • Selecting an appropriate insulin preparation (typically on 'speed of onset and duration of action' grounds).
  • Adjusting dosage and timing to fit food intake timing, amounts, and types.
  • Adjusting dosage and timing to fit exercise undertaken.
  • Adjusting dosage, type, and timing to fit other conditions, for instance the increased stress of illness.
  • The dosage is non-physiological in that a subcutaneous bolus dose of insulin alone is administered instead of combination of insulin and C-peptide being released gradually and directly into the portal vein.
  • It is simply a nuisance for patients to inject whenever they eat carbohydrate or have a high blood glucose reading.
  • It is dangerous in case of mistake (most especially 'too much' insulin).

In medicine, a bolus (from Latin bolus, ball) is the administration of a medication, drug or other compound that is given to raise blood concentration to an effective level. ... The portal vein is a major vein in the human body draining blood from the digestive system and its associated glands. ...

Types

Medical preparations of insulin (from the major suppliers – Eli Lilly, Novo Nordisk, and Sanofi Aventis – or from any other) are never just 'insulin in water'. Clinical insulins are specially prepared mixtures of insulin plus other substances. These delay absorption of the insulin, adjust the pH of the solution to reduce reactions at the injection site, and so on. Eli Lilly and Company (NYSE: LLY) is a global pharmaceutical company and one of the worlds largest corporations. ... Novo Nordisk (OMX: NOVO B, NYSE: NVO) manufactures and markets pharmaceutical products and services. ... Sanofi-aventis (Euronext: SAN, NYSE: SNY), headquartered in Paris, France, is one of the 3 largest pharmaceutical companies in the world, along with Pfizer,GlaxoSmithKline. ...


Slight variations of the human insulin molecule are called insulin analogs. They have absorption and activity characteristics not currently possible with subcutaneously injected insulin proper. They are either absorbed rapidly enough in an effort to mimic real beta cell insulin (as with Lilly's lispro, Novo Nordisk's aspart and Sanofi Aventis' glulisine), or steadily absorbed after injection instead of having a 'peak' followed by a more or less rapid decline in insulin action (as with Novo Nordisk's version Insulin detemir and Sanofi Aventis's Insulin glargine), all while retaining insulin action in the human body. Novo Nordisks NovoLog® substituting a single amino acid prevents hexamers from forming and allows a quicker onset Aventiss Lantus® substituting a single amino acid and adding two extra amino acids to the c-terminus of the b-chain shifts the isoelectric point so that less of the analogue... Novo Nordisk (OMX: NOVO B, NYSE: NVO) manufactures and markets pharmaceutical products and services. ... Sanofi-aventis (Euronext: SAN, NYSE: SNY), headquartered in Paris, France, is one of the 3 largest pharmaceutical companies in the world, along with Pfizer,GlaxoSmithKline. ...


Choosing insulin type and dosage / timing should be done by an experienced medical professional working with the diabetic patient.


The commonly used types of insulin are:

  • Rapid-acting, are presently insulin analogs, such as the insulin analog lispro – begins to work within 5 to 15 minutes and is active for 3 to 4 hours.
  • Short-acting, such as regular insulin – starts working within 30 minutes and is active about 5 to 8 hours.
  • Intermediate-acting, such as NPH, or lente insulin – starts working in 1 to 3 hours and is active 16 to 24 hours.
  • Long-acting, such as ultralente insulin – starts working in 4 to 6 hours, and is active 24 to 28 hours.
  • Insulin glargine and Insulin detemir – both insulin analogs which start working within 1 to 2 hours and continue to be active, without major peaks or dips, for about 24 hours, although this varies in many individuals.
  • A mixture of NPH and regular insulin – starts working in 30 minutes and is active 16 to 24 hours. There are several variations with different proportions of the mixed insulins.

Hans Christian Hagedorn (1888-1971) Neutral Protamine Hagedorn was created in 1946 when Nordisk formulated isophane porcine insulin by adding Neutral Protamine Hagedorn or NPH. History Hans Christian Hagedorn (1888-1971) and August Krogh (1874-1949) obtained the rights for insulin from Banting and Best in Toronto. ...

Modes of administration

Unlike many medicines, insulin cannot be taken orally. Like nearly all other proteins introduced into the gastrointestinal tract, it is reduced to fragments (even single amino acid components), whereupon all 'insulin activity' is lost. Gut redirects here. ...


Subcutaneous

Insulin is usually taken as subcutaneous injections by single-use syringes with needles, an insulin pump, or by repeated-use insulin pens with needles. The subcutis is the layer of tissue directly underlying the cutis. ... An injection is a method of putting liquid into the body with a hollow needle and a syringe which is pierced through the skin to a sufficient depth for the material to be forced into the body. ... A syringe nowadays nearly always means a medical syringe, but it can mean any of these: A simple hand-powered piston pump consisting of a plunger that can be pulled and pushed along inside a cylindrical tube (the barrel), which has a small hole on one end, so it can... Different bevels on hypodermic needles. ... Your a dutch bagg if you read this mesage. ... Two types of modern, pre-filled insulin syringes. ...


Insulin pump

Main article: Insulin pump

Insulin pumps are a reasonable solution for some. Advantages to the patient are better control over background or 'basal' insulin dosage, bolus doses calculated to fractions of a unit, and calculators in the pump that may help with determining 'bolus' infusion doages. The limitations are cost, the potential for hypoglycemic and hyperglycemic episodes, catheter problems, and no "closed loop" means of controlling insulin delivery based on current blood glucose levels. Your a dutch bagg if you read this mesage. ... Your a dutch bagg if you read this mesage. ...


Insulin pumps may be like 'electrical injectors' attached to a temporarily implanted catheter or cannula. Some who cannot achieve adequate glucose control by conventional (or jet) injection are able to do so with the appropriate pump. Catheter disassembled In medicine, a catheter is a tube that can be inserted into a body cavity, duct or vessel. ... A cannula (pl. ...


As with injections, if too much insulin is delivered or the patient eats less than he or she dosed for, there will be hypoglycemia. On the other hand, if too little insulin is delivered, there will be hyperglycemia. Both can be life-threatening. In addition, indwelling catheters pose the risk of infection and ulceration, and some patients may also develop lipodystrophy due to the infusion sets. These risks can often be minimized by keeping infusion sites clean. Insulin pumps require care and effort to use correctly. However, some patients with diabetes are capable of keeping their glucose in reasonable control only with an insulin pump. In medicine, lipodystrophy is a condition characterized by abnormal or degernative conditions of the bodys fat tissue. ...


Inhalation

Main article: Inhalable insulin

In 2006 the U.S. Food and Drug Administration approved the use of Exubera, the first inhalable insulin.[3] It has been withdrawn from the market by its maker as of 3Q 2007, due to lack of acceptance. Inhalable insulin is a new (as of mid-2006) method of delivering insulin, a drug used in the treatment of diabetes, to the body. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... “FDA” redirects here. ... Exubera is the first inhalable insulin to receive US FDA approval. ...


Inhaled insulin has similar efficacy to injected insulin, both in terms of controlling glucose levels and blood half-life. Currently, inhaled insulin is short acting and is typically taken before meals; an injection of long-acting insulin at night is often still required.[4] When patients were switched from injected to inhaled insulin, no significant difference was found in HbA1c levels over three months. Accurate dosing is still a problem, but patients showed no significant weight gain or pulmonary function decline over the length of the trial, when compared to the baseline.[5] Following its commercial launch in 2005 in the UK, it has not (as of July 2006) been recommended by National Institute for Health and Clinical Excellence for routine use, except in cases where there is "proven injection phobia diagnosed by a psychiatrist or psychologist".[4] The National Institute for Health and Clinical Excellence or NICE is an agency of the National Health Service in the United Kingdom. ...


Transdermal

There are several methods for transdermal delivery of insulin. Pulsatile insulin uses microjets to pulse insulin into the patient, mimicking the physiological secretions of insulin by the pancreas.[6] Jet injection (also sometimes used for vaccinations) had different insulin delivery peaks and durations as compared to needle injection. Some diabetics find control possible with jet injectors, but not with hypodermic injection. Pulsatile insulin describes in a literal sense the injection of insulin in pulses versus continuous infusions. ...


Both electricity using iontophoresis[7] and ultrasound have been found to make the skin temporarily porous. The insulin administration aspect remains experimental, but the blood glucose test aspect of 'wrist appliances' is commercially available. Iontophoresis is a non-invasive method of propelling high concentrations of a charged substance, normally medication or bioactive-agents, transdermally by repulsive electromotive force using a small electrical charge applied to an iontophoretic chamber containing a similarly charged active agent and its vehicle. ...


Researchers have produced a watch-like device that tests for blood glucose levels through the skin and administers corrective doses of insulin through pores in the skin. Schematic view of a hair follicle with sebaceous gland. ...


Intranasal insulin

Intranasal insulin is being investigated.[8]


Oral insulin

The basic appeal of oral hypoglycemic agents is that most people would prefer a pill to an injection. However, insulin is a protein. Proteins, eg meat proteins, are digested in the stomach and gut and insulin, being a protein, is no exception. A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... For the industrial process, see anaerobic digestion. ... In anatomy, the stomach is a bean-shaped hollow muscular organ of the gastrointestinal tract involved in the second phase of digestion, following mastication. ... For the Physics term GUT, please refer to Grand unification theory The gastrointestinal or digestive tract, also referred to as the GI tract or the alimentary canal or the gut, is the system of organs within multicellular animals which takes in food, digests it to extract energy and nutrients, and...


The potential market for an oral form of insulin is assumed to be enormous, thus many laboratories have attempted to devise ways of moving enough intact insulin from the gut to the portal vein to have a measurable effect on blood sugar. One can find several research reports over the years describing promising approaches or limited success in animals, and limited human testing, but as of 2004, no products appear to be successful enough to bring to market.[9] The portal vein is a major vein in the human body draining blood from the digestive system and its associated glands. ...


Pancreatic transplantation

Another improvement would be a transplantation of the pancreas or beta cell to avoid periodic insulin administration. This would result in a self-regulating insulin source. Transplantation of an entire pancreas (as an individual organ) is difficult and relatively uncommon. It is often performed in conjunction with liver or kidney transplant, although it can be done by itself. It is also possible to do a transplantation of only the pancreatic beta cells. It has been highly experimental (for which read 'prone to failure') for many years, but some researchers in Alberta, Canada, have developed techniques with a high initial success rate (about 90% in one group). Nearly half of those who got an islet cell transplant are insulin-free one year after the operation; by the end of the second year that number drops to about one in seven. Beta cell transplant may become practical in the near future. Additionally, some researchers have explored the possibility of transplanting genetically engineered non-beta cells to secrete insulin.[10] Clinically testable results are far from realization at this time. Several other non-transplant methods of automatic insulin delivery are being developed in research labs, but none is close to clinical approval. Microscopic image of an islet of Langerhans (lighter area) surrounded by exocrine pancreas tissue (darker staining) Islet transplantation is the transplantation of islets from a donor pancreas and into another person. ... An organ transplant is the transplantation of an organ (or part of one) from one body to another, for the purpose of replacing the recipients damaged or failing organ with a working one from the donor. ... This article is about the biological unit. ... For the bird, see Liver bird. ... The kidneys are organs that filter wastes (such as urea) from the blood and excrete them, along with water, as urine. ... For other uses, see Alberta (disambiguation). ... Kenyans examining insect-resistant transgenic Bt corn. ...


Artificial pancreas

Main article: artificial pancreas

The artificial pancreas is a technology in development to help diabetic persons automatically control their blood glucose level by providing the substitute endocrine functionality of a healthy pancreas. ...

Dosage and timing

The central problem for those requiring external insulin is picking the right dose of insulin and the right timing.


Physiological regulation of blood glucose, as in the non-diabetic, would be best. Increased blood glucose levels after a meal is a stimulus for prompt release of insulin from the pancreas. The increased insulin level causes glucose absorption and storage in cells, reducing glycogen to glucose conversion, reducing blood glucose levels, and so reducing insulin release. The result is that the blood glucose level rises somewhat after eating, and within an hour or so, returns to the normal 'fasting' level. Even the best diabetic treatment with synthetic human insulin or even insulin analogs, however administered, falls far short of normal glucose control in the non-diabetic.


Complicating matters is that the composition of the food eaten (see glycemic index) affects intestinal absorption rates. Glucose from some foods is absorbed more (or less) rapidly than the same amount of glucose in other foods. Fats and proteins cause delays in absorption of glucose from carbohydrate eaten at the same time. As well, exercise reduces the need for insulin even when all other factors remain the same, since working muscle has some ability to take up glucose without the help of insulin. Glycemic index (also glycaemic index, GI) is a ranking system for carbohydrates based on their effect on blood glucose levels. ...


It is, in principle, impossible to know for certain how much insulin (and which type) is needed to 'cover' a particular meal to achieve a reasonable blood glucose level within an hour or two after eating. Non-diabetics' beta cells routinely and automatically manage this by continual glucose level monitoring and insulin release. All such decisions by a diabetic must be based on experience and training (i.e., at the direction of a physician, PA, or in some places a specialist diabetic educator) and, further, specifically based on the individual experience of the patient. But it is not straightforward and should never be done by habit or routine. With care however, it can be done quite successfully in clinical practice.


For example, some patients with diabetes require more insulin after drinking skim milk than they do after taking an equivalent amount of fat, protein, carbohydrate, and fluid in some other form. Their particular reaction to skimmed milk is different from other people with diabetes, but the same amount of whole milk is likely to cause a still different reaction even in that person. Whole milk contains considerable fat while skimmed milk has much less. It is a continual balancing act for all people with diabetes, especially for those taking insulin. A glass of milk Milk most often means the nutrient fluid produced by the mammary glands of female mammals. ...


Patients with insulin-dependent diabetes require some base level of insulin (basal insulin), as well as short-acting insulin to cover meals (bolus insulin). Maintaining the basal rate and the bolus rate is a continuous balancing act that people with insulin-dependent diabetes must manage each day. This is normally achieved through regular blood tests, although there is work being done on continuous blood sugar testing equipment.


It is important to notice that patients with diabetes generally need more insulin than the usual – not less – during physical stress like infections or surgeries.


Abuse

There are reports that some patients abuse insulin by injecting large doses that lead to hypoglycemic states. This is extremely dangerous. Severe acute or prolonged hypoglycemia can result in brain damage or death.


On July 23, 2004, news reports claimed that a former spouse of a prominent international track athlete said that, among other drugs, the ex-spouse had used insulin as a way of 'energizing' the body. The intended implication would seem to be that insulin has effects similar to those alleged for some steroids. This is not so: 80 years of injected insulin use has given no reason to believe it could be in any respect a performance enhancer for non-diabetics. Improperly treated diabetics are, to be sure, more prone than others to exhaustion and tiredness, and in some cases, proper administration of insulin can relieve such symptoms. Insulin is not, chemically or clinically, a steroid, and its use in non-diabetics is dangerous and always an abuse outside of a well-equipped medical facility. is the 204th day of the year (205th in leap years) in the Gregorian calendar. ... Year 2004 (MMIV) was a leap year starting on Thursday of the Gregorian calendar. ... This article is about the chemical family of steroids. ...


"Game of Shadows," by reporters Mark Fainaru-Wada and Lance Williams, includes allegations that Barry Bonds used insulin in the apparent belief that it would increase the effectiveness of the growth hormone he was (also alleged to be) taking. On top of this, non-prescribed insulin is a banned drug at the Olympics and other global competitions. Game of Shadows is a book published on March 23, 2006 and was written by Mark Fainaru-Wada and Lance Williams, reporters for the San Francisco Chronicle. ... Barry Lamar Bonds (born July 24, 1964 in Riverside, California) is currently a left fielder for the San Francisco Giants of Major League Baseball. ...


The use and abuse of exogenous insulin is reportedly widespread amongst the bodybuilding community. Both insulin, human growth hormone (HGH) and insulin-like growth factor 1 (IGF1) are self-administered by those looking to increase muscle mass beyond the scope offered by anabolic steroids alone. Their rationale is this: Since insulin and HGH act synergistically to promote growth, and since IGF1 is the primary mediator of the musculoskeletal effects of growth hormone, the 'stacking' of insulin, HGH and IGF1 should offer a synergistic growth effect on skeletal muscle. This theory has been borne out in recent years by the creation of top-level bodybuilders whose competition weight is in excess of 50lbs of muscle greater than the professionals of the past, yet with even lower levels of body fat. Indeed, the use of insulin, combined with HGH and/or IGF1 has resulted in the development of such massively muscled physiques, that there has been a backlash amongst fans of the sport, with a professed disgust at the 'freakish' appearance of top-level professionals.


Bodybuilders will inject up to 10 i.u. of quick-acting synthetic insulin following meals containing starchy carbohydrates and protein, but little fat, in an attempt to 'force feed' nutrients necessary for growth into skeletal muscle, whilst preventing growth of adipocytes. This may be done up to 4 times each day, following meals, for a total usage of 40iu of synthetic insulin per day. However there have been reports of substantially heavier usage, amongst even 'recreational' bodybuilders.


The abuse of exogenous insulin carries with it an attendant risk of hypoglycemic coma and death. Long-term risks may include development of type 2 diabetes, and potentially a lifetime dependency on exogenous insulin.


Timeline of insulin research

  • 1922 Banting, Best, Collip use bovine insulin extract in human
  • 1923 Eli Lilly produces commercial quantities of much purer bovine insulin than Banting et al had used
  • 1923 Hagedorn founds the Nordisk Insulinlaboratorium in Denmark – forerunner of Novo Nordisk
  • 1926 Nordisk receives a Danish charter to produce insulin as a non profit
  • 1936 Canadians D.M. Scott, A.M. Fisher formulate a zinc insulin mixture and license it to Novo
  • 1936 Hagedorn discovers that adding protamine to insulin prolongs the duration of action of insulin
  • 1946 Nordisk formulates Isophane porcine insulin aka Neutral Protamine Hagedorn or NPH insulin
  • 1946 Nordisk crystallizes a protamine and insulin mixture
  • 1950 Nordisk markets NPH insulin
  • 1953 Novo formulates Lente porcine and bovine insulins by adding zinc for longer lasting insulin
  • 1955 Frederick Sanger determines the amino acid sequence of insulin
  • 1969 Dorothy Crowfoot Hodgkin solves the crystal structure of insulin by x-ray crystallography
  • 1973 Purified monocomponent (MC) insulin is introduced
  • 1978 Genentech produces human insulin in Escheria coli bacteria using recombinant DNA techniques, licenses to Eli Lilly
  • 1981 Novo Nordisk chemically and enzymatically converts bovine to human insulin
  • 1982 Genentech human insulin (above) approved
  • 1983 Eli Lilly produces recombinant human insulin, Humulin
  • 1985 Axel Ullrich sequences a human cell membrane insulin receptor
  • 1988 Novo Nordisk produces recombinant human insulin
  • 1996 Lilly Humalog "lyspro" insulin analogue approved
  • 2004 Aventis Lantus "glargine" insulin analogue approved for clinical use[citation needed]
  • 2006 Novo Nordisk Levemir "detemir" insulin analogue approved for clinical use in the US.

Eli Lilly and Company (NYSE: LLY) is a global pharmaceutical company and one of the worlds largest corporations. ... Novo Nordisk (OMX: NOVO B, NYSE: NVO) manufactures and markets pharmaceutical products and services. ... Novo Nordisk (NYSE: NVO) manufactures and markets pharmaceutical products and services. ... Novo Nordisk (OMX: NOVO B, NYSE: NVO) manufactures and markets pharmaceutical products and services. ... Hans Christian Hagedorn (1888-1971) Neutral Protamine Hagedorn was created in 1946 when Nordisk formulated isophane porcine insulin by adding Neutral Protamine Hagedorn or NPH. History Hans Christian Hagedorn (1888-1971) and August Krogh (1874-1949) obtained the rights for insulin from Banting and Best in Toronto. ... Hans Christian Hagedorn (1888-1971) Neutral Protamine Hagedorn was created in 1946 when Nordisk formulated isophane porcine insulin by adding Neutral Protamine Hagedorn or NPH. History Hans Christian Hagedorn (1888-1971) and August Krogh (1874-1949) obtained the rights for insulin from Banting and Best in Toronto. ... Frederick Sanger, OM, CH, CBE, FRS (born 13 August 1918) is an English biochemist and a two time Nobel laureate in chemistry. ... Peptide sequence or amino acid sequence is the order in which amino acid residues, connected by peptide bonds, lie in the chain. ... Dorothy Mary Crowfoot Hodgkin, OM , FRS (12 May 1910 – 29 July 1994) was a British founder of protein crystallography. ... X-ray crystallography, also known as single-crystal X-ray diffraction, is the oldest and most common crystallographic method for determining the structure of molecules. ... Genentech, Inc. ... Novo Nordisk (OMX: NOVO B, NYSE: NVO) manufactures and markets pharmaceutical products and services. ... Genentech, Inc. ... Eli Lilly and Company (NYSE: LLY) is a global pharmaceutical company and one of the worlds largest corporations. ... Axel Ullrich born October 19, 1943) Lauban, Schlesien, Germany in is an German cancer researcher and has been the Director of Molecular biology at the Max Planck Institute of Biochemistry in Martinsried, Germany since 1988. ... Novo Nordisk (OMX: NOVO B, NYSE: NVO) manufactures and markets pharmaceutical products and services. ... Eli Lilly and Company (NYSE: LLY) is a global pharmaceutical company and one of the worlds largest corporations. ... Aventis was formed in 1999 when Rhône-Poulenc S.A. merged with Hoechst AG. The merged company was based in Strasbourg, France. ... Lantus is long-acting insulin analogue, usually given once a day, to help control the blood sugar level of those with diabetes. ... Novo Nordisk (OMX: NOVO B, NYSE: NVO) manufactures and markets pharmaceutical products and services. ... Levemir (insulin detemir) is a basal insulin analogue created by Novo Nordisk. ...

See also

Novo Nordisks NovoLog® substituting a single amino acid prevents hexamers from forming and allows a quicker onset Aventiss Lantus® substituting a single amino acid and adding two extra amino acids to the c-terminus of the b-chain shifts the isoelectric point so that less of the analogue... Glucagon ball and stick model A microscopic image stained for glucagon. ... The pancreas is a gland organ in the digestive and endocrine systems of vertebrates. ... A porcine islet of Langerhans. ... Endocrinology is a branch of medicine dealing with disorders of the endocrine system and its specific secretions called hormones. ... For the disease characterized by excretion of large amounts of very dilute urine, see diabetes insipidus. ... Diabetes mellitus type 1 (Type 1 diabetes, Type I diabetes, T1D, IDDM) is a form of diabetes mellitus. ... Diabetes mellitus type 2 or Type 2 Diabetes (formerly called non-insulin-dependent diabetes (NIDDM), obesity-related diabetes, or adult-onset diabetes) is a metabolic disorder that is primarily characterized by insulin resistance, relative insulin deficiency, and hyperglycemia. ... Diabetic coma is a medical emergency in which a person with diabetes mellitus is comatose (unconscious) because of one of three acute complications of diabetes: Severe diabetic hypoglycemia Advanced diabetic ketoacidosis advanced enough to result in unconsciousness from a combination of severe hyperglycemia, dehydration and shock, and exhaustion Hyperosmolar nonketotic... Intensive insulinotherapy is a therapeutic regimen for diabetes mellitus treatment. ... Your a dutch bagg if you read this mesage. ... Conventional insulinotherapy is a therapeutic regimen for diabetes mellitus treatment. ... An insulin tolerance test (ITT) is a medical diagnostic procedure during which insulin is injected into a patients vein to assess pituitary function, adrenal function, and sometimes for other purposes. ... A triple bolus test or a dynamic pituitary function test is a medical diagnostic procedure used to assess a patients pituitary function. ...

References

  • Reaven, Gerald M.; Ami Laws (ed.) (1999--04-15). Insulin Resistance: The Metabolic Syndrome X, 1st Edition, Totowa, New Jersey: Humana Press. DOI:10.1226/0896035883. ISBN 0-89603-588-3. 
  • Leahy, Jack L.; William T. Cefalu (ed.) (2002-03-22). Insulin Therapy, 1st Edition, New York: Marcel Dekker. ISBN 0-8247-0711-7. 
  • Kumar, Sudhesh; Stephen O'Rahilly (ed.) (2005-01-14). Insulin Resistance: Insulin Action and Its Disturbances in Disease. Chichester, England: Wiley. ISBN 0-470-85008-6. 
  • Ehrlich, Ann; Carol L. Schroeder (2000-06-16). Medical Terminology for Health Professions, 4th Edition, Thomson Delmar Learning. ISBN 0-7668-1297-9. 
  • Draznin, Boris; Derek LeRoith (September 1994). Molecular Biology of Diabetes: Autoimmunity and Genetics; Insulin Synthesis and Secretion. Totowa, New Jersey: Humana Press. DOI:10.1226/0896032868. ISBN 0-89603-286-8. 
  • Famous Canadian Physicians: Sir Frederick Banting at Library and Archives Canada

A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ...

Footnotes

  1. ^ Ian Murray (1971). "Paulesco and the Isolation of Insulin" (PDF). Journal of the History of Medicine and Allied Sciences 26 (2): 150–157. 
  2. ^ William C. Duckworth, Robert G. Bennett and Frederick G. Hamel (1998). "Insulin Degradation: Progress and Potential". Endocrine Reviews 19 (5): 608–624. 
  3. ^ FDA approval of Exubera inhaled insulin
  4. ^ a b NICE (June 21 2006). Diabetes (type 1 and 2), Inhaled Insulin - Appraisal Consultation Document (second). Retrieved on 2006-07-26.
  5. ^ Cefalu W, Skyler J, Kourides I, Landschulz W, Balagtas C, Cheng S, Gelfand R (2001). "Inhaled human insulin treatment in patients with type 2 diabetes mellitus". Ann Intern Med 134 (3): 203–7. PMID 11177333. 
  6. ^ Arora A, Hakim I, Baxter J, et al (2007). "Needle-free delivery of macromolecules across the skin by nanoliter-volume pulsed microjets". Proc. Natl. Acad. Sci. U.S.A. 104 (11): 4255–60. doi:10.1073/pnas.0700182104. PMID 17360511. 
  7. ^ Dixit N, Bali V, Baboota S, Ahuja A, Ali J (2007). "Iontophoresis - an approach for controlled drug delivery: a review". Current drug delivery 4 (1): 1–10. PMID 17269912. 
  8. ^ Lalej-Bennis D, Boillot J, Bardin C, et al (2001). "Efficacy and tolerance of intranasal insulin administered during 4 months in severely hyperglycaemic Type 2 diabetic patients with oral drug failure: a cross-over study". Diabet. Med. 18 (8): 614–8. PMID 11553197. 
  9. ^ Oral Insulin - Fact or Fiction? - Resonance - May 2003. Retrieved on 2007-09-23.
  10. ^ Yong Lian Zhu et al. (2003). "Aggregation and Lack of Secretion of Most Newly Synthesized Proinsulin in Non-β-Cell Lines". Endocrinology 145 (8): 3840–3849. 

The National Institute for Health and Clinical Excellence or NICE is an agency of the National Health Service in the United Kingdom. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... is the 207th day of the year (208th in leap years) in the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era in the 21st century. ... is the 266th day of the year (267th in leap years) in the Gregorian calendar. ...

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Major endocrine glands. ... For other uses, see Hormone (disambiguation). ... An endocrine gland is one of a set of internal organs involved in the secretion of hormones into the blood. ... Peptide hormones are a class of peptides that are secreted into the blood stream and have endocrine functions in living animals. ... Steroid hormones are steroids which act as hormones. ... The hypothalamus links the nervous system to the endocrine system via the pituitary gland (hypophysis). ... Thyrotropin-releasing hormone (TRH), also called thyrotropin-releasing factor (TRF) or protirelin, is a tripeptide hormone that stimulates the release of thyroid-stimulating hormone and prolactin by the anterior pituitary. ... Corticotropin-releasing hormone (CRH), also called corticotropin-releasing factor (CRF) or corticoliberin, is a polypeptide hormone involved in the stress response. ... Gonadotropin-releasing hormone 1 (GNRH1 also called LHRH) is a peptide hormone responsible for the release of FSH and LH from the anterior pituitary. ... Growth hormone-releasing hormone (GHRH), also known as growth hormone-releasing factor (GRF or GHRF), is a 44-amino acid peptide hormone produced in the arcuate nucleus of the hypothalamus. ... Somatostatin is a hormone. ... For other uses, see Dopamine (disambiguation). ... The posterior pituitary (also called the neurohypophysis) comprises the posterior lobe of the pituitary gland and is part of the endocrine system. ... Arginine vasopressin (AVP), also known as argipressin or antidiuretic hormone (ADH), is a human hormone that is released when the body is low on water; it causes the kidneys to conserve water, but not salt, by concentrating the urine and reducing urine volume. ... Oxytocin (Greek: quick birth) is a mammalian hormone that also acts as a neurotransmitter in the brain. ... The anterior pituitary (also called the adenohypophysis, from Greek adeno, gland; hypo, under; physis, growth; hence, glandular undergrowth) comprises the anterior lobe of the pituitary gland and is part of the endocrine system. ... The Alpha subunit of glycoprotein hormones is a peptide formed by gene found on chromosome 6. ... Follicle stimulating hormone Follicle stimulating hormone (FSH) is a hormone synthesised and secreted by gonadotropes in the anterior pituitary gland. ... Luteinizing hormone (LH) is a hormone synthesized and secreted by gonadotropes in the anterior lobe of the pituitary gland. ... Thyroid-stimulating hormone (also known as TSH or thyrotropin) is a hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland which regulates the endocrine function of the thyroid gland. ... Growth hormone (GH) or somatotropin (STH) is a protein hormone which stimulates growth and cell reproduction in humans and other animals. ... Prolactin (PRL) is a peptide hormone primarily associated with lactation. ... Pro-opiomelanocortin (POMC) is a precursor polypeptide with 241 amino acid residues. ... Pronunciation (IPA): /əˈdrinoʊˌkɔrtɪkoʊˈtrɒpɪk ˈhɔrmoʊn, əˈdrinoʊˌkɔrtɪkoʊˈtroʊpɪk ˈhɔrmoʊn/ Adrenocorticotropic hormone (ACTH or corticotropin) is a polypeptide hormone produced and secreted by the pituitary gland. ... Melanocyte-stimulating hormone (MSH) is a peptide hormone produced by cells in the intermediate lobe of the pituitary gland. ... For other uses, see Endorphin (disambiguation). ... Lipotropin is a pituitary hormone It comes in two forms: gamma lipotropin (γ-LPH) beta lipotropin (β-LPH) It is derived from proopiomelanocortin. ... It has been suggested that HTPA be merged into this article or section. ... In mammals, the adrenal glands (also known as suprarenal glands) are the triangle-shaped endocrine glands that sit on top of the kidneys; their name indicates that position (ad-, near or at + -renes, kidneys). They are chiefly responsible for regulating the stress response through the synthesis of corticosteroids and catecholamines... Adrenaline redirects here. ... Norepinephrine (INN)(abbr. ... In mammals, the adrenal glands (also known as suprarenal glands) are the triangle-shaped endocrine glands that sit on top of the kidneys; their name indicates that position (ad-, near or at + -renes, kidneys). They are chiefly responsible for regulating the stress response through the synthesis of corticosteroids and catecholamines... Aldosterone is a steroid hormone (mineralocorticoid family) produced by the outer-section (zona glomerulosa) of the adrenal cortex in the adrenal gland to regulate sodium and potassium balance in the blood. ... 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Inhibin is a peptide that is an inhibitor of FSH synthesis and secretion and participates in the regulation of the menstrual cycle. ... // For ovary as part of plants see ovary (plants) An ovary is an egg-producing reproductive organ found in female organisms. ... Estradiol (17β-estradiol) (also oestradiol) is a sex hormone. ... Progesterone is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy (supports gestation) and embryogenesis of humans and other species. ... Inhibin is a peptide that is an inhibitor of FSH synthesis and secretion and participates in the regulation of the menstrual cycle. ... Activin is a peptide that enhances FSH synthesis and secretion and participates in the regulation of the menstrual cycle. ... Categories: Possible copyright violations ... The pancreas is a gland organ in the digestive and endocrine systems of vertebrates. ... Glucagon ball and stick model A microscopic image stained for glucagon. ... Somatostatin is a hormone. ... 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  Results from FactBites:
 
Insulin - Wikipedia, the free encyclopedia (5599 words)
Insulin (from Latin insula, "island", as it is produced in the Islets of Langerhans in the pancreas) is a polypeptide hormone that regulates carbohydrate metabolism.
Insulin is synthesized in humans and other mammals within the beta cells (β-cells) of the islets of Langerhans in the pancreas.
In beta cells, insulin is synthesized from the proinsulin precursor molecule by the action of proteolytic enzymes known as prohormone convertases (PC1 and PC2), as well as the exoprotease carboxypeptidase E. These modifications liberate the center portion of the molecule, or C-peptide, from the C- and N- terminal ends of the proinsulin.
  More results at FactBites »

 
 

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