Insulin (/ˈɪn.sjʊ.lɪn/,[5][6] from Latin insula, 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (INS) gene. It is the main anabolic hormone of the body.[7] It regulates the metabolism of carbohydrates, fats, and protein by promoting the absorption of glucose from the blood into cells of the liver, fat, and skeletal muscles.[8] In these tissues the absorbed glucose is converted into either glycogen, via glycogenesis, or fats (triglycerides), via lipogenesis; in the liver, glucose is converted into both.[8] Glucose production and secretion by the liver are strongly inhibited by high concentrations of insulin in the blood.[9] Circulating insulin also affects the synthesis of proteins in a wide variety of tissues. It is thus an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules in the cells. Low insulin in the blood has the opposite effect, promoting widespread catabolism, especially of reserve body fat.
Beta cells are sensitive to blood sugar levels so that they secrete insulin into the blood in response to high level of glucose, and inhibit secretion of insulin when glucose levels are low.[10] Insulin production is also regulated by glucose: high glucose promotes insulin production while low glucose levels lead to lower production.[11] Insulin enhances glucose uptake and metabolism in the cells, thereby reducing blood sugar. Their neighboring alpha cells, by taking their cues from the beta cells,[10] secrete glucagon into the blood in the opposite manner: increased secretion when blood glucose is low, and decreased secretion when glucose concentrations are high. Glucagon increases blood glucose by stimulating glycogenolysis and gluconeogenesis in the liver.[8][10] The secretion of insulin and glucagon into the blood in response to the blood glucose concentration is the primary mechanism of glucose homeostasis.[10]
Decreased or absent insulin activity results in diabetes, a condition of high blood sugar level (hyperglycaemia). There are two types of the disease. In type 1 diabetes, the beta cells are destroyed by an autoimmune reaction so that insulin can no longer be synthesized or be secreted into the blood.[12] In type 2 diabetes, the destruction of beta cells is less pronounced than in type 1, and is not due to an autoimmune process. Instead, there is an accumulation of amyloid in the pancreatic islets, which likely disrupts their anatomy and physiology.[10] The pathogenesis of type 2 diabetes is not well understood but reduced population of islet beta-cells, reduced secretory function of islet beta-cells that survive, and peripheral tissue insulin resistance are known to be involved.[7] Type 2 diabetes is characterized by increased glucagon secretion which is unaffected by, and unresponsive to the concentration of blood glucose. But insulin is still secreted into the blood in response to the blood glucose.[10] As a result, glucose accumulates in the blood.
The human insulin protein is composed of 51 amino acids, and has a molecular mass of 5808 Da. It is a heterodimer of an A-chain and a B-chain, which are linked together by disulfide bonds. Insulin's structure varies slightly between species of animals. Insulin from non-human animal sources differs somewhat in effectiveness (in carbohydrate metabolism effects) from human insulin because of these variations. Porcine insulin is especially close to the human version, and was widely used to treat type 1 diabetics before human insulin could be produced in large quantities by recombinant DNA technologies.[13][14][15][16]
Insulin was the first peptide hormone discovered.[17] Frederick Banting and Charles Best, working in the laboratory of John Macleod at the University of Toronto, were the first to isolate insulin from dog pancreas in 1921. Frederick Sanger sequenced the amino acid structure in 1951, which made insulin the first protein to be fully sequenced.[18] The crystal structure of insulin in the solid state was determined by Dorothy Hodgkin in 1969. Insulin is also the first protein to be chemically synthesised and produced by DNA recombinant technology.[19] It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.[20]
- ^ a b c GRCh38: Ensembl release 89: ENSG00000254647 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000000215 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Insulin | Meaning of Insulin by Lexico". Lexico Dictionaries | English. Archived from the original on 1 August 2020.
- ^ "insulin - WordReference.com Dictionary of English". www.wordreference.com.
- ^ a b Voet D, Voet JG (2011). Biochemistry (4th ed.). New York: Wiley.
- ^ a b c Stryer L (1995). Biochemistry (Fourth ed.). New York: W.H. Freeman and Company. pp. 773–74. ISBN 0-7167-2009-4.
- ^ Sonksen P, Sonksen J (July 2000). "Insulin: understanding its action in health and disease". British Journal of Anaesthesia. 85 (1): 69–79. doi:10.1093/bja/85.1.69. PMID 10927996.
- ^ a b c d e f Koeslag JH, Saunders PT, Terblanche E (June 2003). "A reappraisal of the blood glucose homeostat which comprehensively explains the type 2 diabetes mellitus-syndrome X complex". The Journal of Physiology. 549 (Pt 2) (published 2003): 333–46. doi:10.1113/jphysiol.2002.037895. PMC 2342944. PMID 12717005.
- ^ Andrali SS, Sampley ML, Vanderford NL, Ozcan S (1 October 2008). "Glucose regulation of insulin gene expression in pancreatic beta-cells". The Biochemical Journal. 415 (1): 1–10. doi:10.1042/BJ20081029. ISSN 1470-8728. PMID 18778246.
- ^ American Society of Health-System Pharmacists (1 February 2009). "Insulin Injection [". PubMed Health. National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 12 October 2012.
- ^ Drug Information Portal NLM – Insulin human USAN druginfo.nlm.nih.gov Archived 19 November 2022 at the Wayback Machine
- ^ "First Successful Laboratory Production of Human Insulin Announced". News Release. Genentech. 6 September 1978. Archived from the original on 27 September 2016. Retrieved 26 September 2016.
- ^ Tof I (1994). "Recombinant DNA technology in the synthesis of human insulin". Little Tree Publishing. Retrieved 3 November 2009.
- ^ Aggarwal SR (December 2012). "What's fueling the biotech engine-2011 to 2012". Nature Biotechnology. 30 (12): 1191–7. doi:10.1038/nbt.2437. PMID 23222785. S2CID 8707897.
- ^ Weiss M, Steiner DF, Philipson LH (2000). "Insulin Biosynthesis, Secretion, Structure, and Structure-Activity Relationships". In Feingold KR, Anawalt B, Boyce A, Chrousos G, Dungan K, Grossman A, et al. (eds.). Endotext. MDText.com, Inc. PMID 25905258. Retrieved 18 February 2020.
- ^ Cite error: The named reference
Stretton_2002was invoked but never defined (see the help page). - ^ "The discovery and development of insulin as a medical treatment can be traced back to the 19th century". Diabetes. 15 January 2019. Retrieved 17 February 2020.
- ^ 19th WHO Model List of Essential Medicines (April 2015) (PDF). WHO. April 2015. p. 455. hdl:10665/189763. ISBN 978-92-4-120994-6. Retrieved 10 May 2015.