insulin insulin insulin (/ˈɪn.sjʊ.lɪn/, from latin insula, 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ins gene. it is considered to be the main anabolic hormone of the body. it regulates the metabolism of carbohydrates, fats and protein by promoting the absorption of glucose from the blood into liver, fat and skeletal muscle cells. in these tissues the absorbed glucose is converted into either glycogen via glycogenesis or fats (triglycerides) via lipogenesis, or, in the case of the liver, into both. glucose production and secretion by the liver is strongly inhibited by high concentrations of insulin in the blood. circulating insulin also affects the synthesis of proteins in a wide variety of tissues. it is therefore an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules inside the cells. low insulin levels in the blood have the opposite effect by promoting widespread catabolism, especially of reserve body fat. this article is about the naturally occurring protein. for uses of insulin in treating diabetes, see insulin (medication). insavailable structurespdbortholog search: pdbe rcsb list of pdb id codes1a7f, 1ai0, 1aiy, 1b9e, 1ben, 1ev3, 1ev6, 1evr, 1fu2, 1fub, 1g7a, 1g7b, 1guj, 1hiq, 1his, 1hit, 1hls, 1htv, 1hui, 1iog, 1ioh, 1j73, 1jca, 1jco, 1k3m, 1kmf, 1lkq, 1lph, 1mhi, 1mhj, 1mso, 1os3, 1os4, 1q4v, 1qiy, 1qiz, 1qj0, 1rwe, 1sf1, 1t1k, 1t1p, 1t1q, 1trz, 1tyl, 1tym, 1uz9, 1vkt, 1w8p, 1xda, 1xgl, 1xw7, 1zeg, 1zeh, 1znj, 2aiy, 2c8q, 2c8r, 2ceu, 2h67, 2hh4, 2hho, 2hiu, 2jmn, 2jum, 2juu, 2juv, 2jv1, 2jzq, 2k91, 2k9r, 2kjj, 2kju, 2kqq, 2kxk, 2l1y, 2l1z, 2lgb, 2m1d, 2m1e, 2m2m, 2m2n, 2m2o, 2m2p, 2oly, 2olz, 2om0, 2om1, 2omg, 2omh, 2omi, 2qiu, 2r34, 2r35, 2r36, 2rn5, 2vjz, 2vk0, 2w44, 2wby, 2wc0, 2wru, 2wrv, 2wrw, 2wrx, 2ws0, 2ws1, 2ws4, 2ws6, 2ws7, 3aiy, 3bxq, 3e7y, 3e7z, 3exx, 3fq9, 3i3z, 3i40, 3ilg, 3inc, 3ir0, 3q6e, 3rov, 3tt8, 3u4n, 3utq, 3uts, 3utt, 3v19, 3v1g, 3w11, 3w12, 3w13, 3w7y, 3w7z, 3w80, 3zi3, 3zqr, 3zs2, 3zu1, 4aiy, 4ajx, 4ajz, 4ak0, 4akj, 4efx, 4eww, 4ewx, 4ewz, 4ex0, 4ex1, 4exx, 4ey1, 4ey9, 4eyd, 4eyn, 4eyp, 4f0n, 4f0o, 4f1a, 4f1b, 4f1c, 4f1d, 4f1f, 4f1g, 4f4t, 4f4v, 4f51, 4f8f, 4fg3, 4fka, 4gbc, 4gbi, 4gbk, 4gbl, 4gbn, 4iuz, 5aiy, 2lwz, 3jsd, 3kq6, 3p2x, 3p33, 1jk8, 2mli, 2mpg, 2mpi, 2mvc, 2mvd, 4cxl, 4cxn, 4cy7, 4nib, 4oga, 4p65, 4q5z, 4rxw, 4une, 4ung, 4unh, 4xc4, 4wdi, 4z76, 4z77, 4z78, 2n2w, 5co6, 5ena, 4y19, 5bqq, 5boq, 2n2v, 5cny, 5co9, 5en9, 4y1a, 2n2x, 5bpo, 5co2, 5bts, 5hyj, 5c0d,%%s1efe, 1sjt, 1sju, 2kqp,%%s1t0c,%%s2g54, 2g56, 3hyd, 2omqidentifiersaliasesins, iddm, iddm1, iddm2, ilpr, irdn, mody10, insulin, pndm4external idsomim: 176730 mgi: 96573 homologene: 173 genecards: ins gene location (human)chr.chromosome 11 (human)band11p15.5start2,159,779 bpend2,161,221 bpgene location (mouse)chr.chromosome 7 (mouse)band7 f5|7 88.0 cmstart142,232,393 bpend142,297,118 bprna expression patternbgeehumanmouse (ortholog)top expressed inbeta cellbody of pancreasright lobe of liverright adrenal glandleft adrenal glandleft uterine tuberight coronary arterycanal of the cervixfundussubstantia nigratop expressed inislet of langerhanspyloric antrumyolk sacretinal pigment epitheliumsecondary oocytequadriceps femoris muscleanklesexually immature organismneuronspermatidmore reference expression databiogpsmore reference expression datagene ontologymolecular function insulin receptor binding identical protein binding protease binding insulin-like growth factor receptor binding protein binding hormone activity cellular component endoplasmic reticulum lumen transport vesicle golgi membrane secretory granule lumen golgi lumen endoplasmic reticulum-golgi intermediate compartment membrane endosome lumen extracellular region extracellular space biological process negative regulation of nad(p)h oxidase activity positive regulation of dna replication positive regulation of mapk cascade positive regulation of brown fat cell differentiation positive regulation of cell differentiation mapk cascade positive regulation of respiratory burst positive regulation of phosphatidylinositol 3-kinase signaling negative regulation of protein oligomerization positive regulation of nf-kappab transcription factor activity negative regulation of respiratory burst involved in inflammatory response cell-cell signaling positive regulation of nitric oxide biosynthetic process positive regulation of glycolytic process positive regulation of nitric-oxide synthase activity positive regulation of protein autophosphorylation activation of protein kinase b activity wound healing positive regulation of mitotic nuclear division negative regulation of feeding behavior positive regulation of peptide hormone secretion negative regulation of protein catabolic process positive regulation of cell migration acute-phase response regulation of protein secretion positive regulation of glycogen biosynthetic process positive regulation of protein kinase b signaling g protein-coupled receptor signaling pathway regulation of cellular amino acid metabolic process negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway endoplasmic reticulum to golgi vesicle-mediated transport negative regulation of lipid catabolic process positive regulation of cell growth negative regulation of glycogen catabolic process positive regulation of insulin receptor signaling pathway glucose metabolic process negative regulation of acute inflammatory response negative regulation of protein secretion positive regulation of peptidyl-tyrosine phosphorylation glucose homeostasis positive regulation of cell population proliferation fatty acid homeostasis positive regulation of protein metabolic process regulation of transmembrane transporter activity negative regulation of gluconeogenesis negative regulation of fatty acid metabolic process regulation of protein localization regulation of transcription, dna-templated positive regulation of lipid biosynthetic process carbohydrate metabolic process negative regulation of proteolysis alpha-beta t cell activation positive regulation of protein localization to nucleus positive regulation of glucose import insulin receptor signaling pathway positive regulation of gene expression regulation of signaling receptor activity positive regulation of nitric oxide mediated signal transduction regulation of synaptic plasticity cognition positive regulation of long-term synaptic potentiation positive regulation of dendritic spine maintenance regulation of protein localization to plasma membrane negative regulation of reactive oxygen species biosynthetic process neuron projection maintenance response to l-arginine signal transduction sources:amigo / quickgoorthologsspecieshumanmouseentrez363016334ensemblensg00000254647ensmusg00000000215uniprotp01308p01326refseq (mrna)nm_000207nm_001185097nm_001185098nm_001291897nm_001185083nm_001185084nm_008387refseq (protein)np_000198np_001172026np_001172027np_001278826np_000198.1np_001172026.1np_001172027.1np_001278826.1np_000198np_000198np_000198np_000198np_001172012np_001172013np_032413location (ucsc)chr 11: 2.16 – 2.16 mbchr 7: 142.23 – 142.3 mbpubmed searchwikidataview/edit humanview/edit mouse insulin is a peptide hormone containing two chains cross-linked by disulfide bridges. 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. insulin enhances glucose uptake and metabolism in the cells, thereby reducing blood sugar level. their neighboring alpha cells, by taking their cues from the beta cells, 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 level by stimulating glycogenolysis and gluconeogenesis in the liver. the secretion of insulin and glucagon into the blood in response to the blood glucose concentration is the primary mechanism of glucose homeostasis. decreased or absent insulin activity results in diabetes mellitus, a condition of high blood sugar level (hyperglycaemia). there are two types of the disease. in diabetes mellitus type 1, the beta cells are destroyed by an autoimmune reaction so that insulin can no longer be synthesized or be secreted into the blood. in diabetes mellitus type 2, 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. 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. 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. 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. insulin was the first peptide hormone discovered. frederick banting and charles herbert best, working in the laboratory of j. j. r. 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. 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. it is on the who model list of essential medicines, the most important medications needed in a basic health system. evolution and species distribution insulin may have originated more than a billion years ago. the molecular origins of insulin go at least as far back as the simplest unicellular eukaryotes. apart from animals, insulin-like proteins are also known to exist in fungi and protists. insulin is produced by beta cells of the pancreatic islets in most vertebrates and by the brockmann body in some teleost fish. cone snails: conus geographus and conus tulipa, venomous sea snails that hunt small fish, use modified forms of insulin in their venom cocktails. the insulin toxin, closer in structure to fishes' than to snails' native insulin, slows down the prey fishes by lowering their blood glucose levels. production diagram of insulin regulation upon high blood glucose insulin is produced exclusively in the beta cells of the pancreatic islets in mammals, and the brockmann body in some fish. human insulin is produced from the ins gene, located on chromosome 11. rodents have two functional insulin genes; one is the homolog of most mammalian genes (ins2), and the other is a retroposed copy that includes promoter sequence but that is missing an intron (ins1). transcription of the insulin gene increases in response to elevated blood glucose. this is primarily controlled by transcription factors that bind enhancer sequences in the ~400 base pairs before the gene's transcription start site. the major transcription factors influencing insulin secretion are pdx1, neurod1, and mafa. during a low-glucose state, pdx1 (pancreatic and duodenal homeobox protein 1) is located in the nuclear periphery as a result of interaction with hdac1 and 2, which results in downregulation of insulin secretion. an increase in blood glucose levels causes phosphorylation of pdx1, which leads it to undergo nuclear translocation and bind the a3 element within the insulin promoter. upon translocation it interacts with coactivators hat p300 and setd7. pdx1 affects the histone modifications through acetylation and deacetylation as well as methylation. it is also said to suppress glucagon. neurod1, also known as β2, regulates insulin exocytosis in pancreatic β cells by directly inducing the expression of genes involved in exocytosis. it is localized in the cytosol, but in response to high glucose it becomes glycosylated by ogt and/or phosphorylated by erk, which causes translocation to the nucleus. in the nucleus β2 heterodimerizes with e47, binds to the e1 element of the insulin promoter and recruits co-activator p300 which acetylates β2. it is able to interact with other transcription factors as well in activation of the insulin gene. mafa is degraded by proteasomes upon low blood glucose levels. increased levels of glucose make an unknown protein glycosylated. this protein works as a transcription factor for mafa in an unknown manner and mafa is transported out of the cell. mafa is then translocated back into the nucleus where it binds the c1 element of the insulin promoter. these transcription factors work synergistically and in a complex arrangement. increased blood glucose can after a while destroy the binding capacities of these proteins, and therefore reduce the amount of insulin secreted, causing diabetes. the decreased binding activities can be mediated by glucose induced oxidative stress and antioxidants are said to prevent the decreased insulin secretion in glucotoxic pancreatic β cells. stress signalling molecules and reactive oxygen species inhibits the insulin gene by interfering with the cofactors binding the transcription factors and the transcription factors itself. several regulatory sequences in the promoter region of the human insulin gene bind to transcription factors. in general, the a-boxes bind to pdx1 factors, e-boxes bind to neurod, c-boxes bind to mafa, and camp response elements to creb. there are also silencers that inhibit transcription. synthesis 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.