In molecular biology, the insulin receptor is a transmembrane receptor that is activated by insulin. It belongs to the large class of tyrosine kinase receptors. Hugo is a masculine name. ... 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. ... The National Center for Biotechnology Information (NCBI) is part of the US National Library of Medicine (NLM), which is a branch of the US National Institutes of Health. ... 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. ... Short and long arms Chromosome. ... Chromosome 19 is one of the 23 pairs of chromosomes in humans. ... Molecular biology is the study of biology at a molecular level. ... Transmembrane receptors are integral membrane proteins, which reside and operate typically within a cells plasma membrane, but also in the membranes of some subcellular compartments and organelles. ... In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm that binds to a specific factor (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ... 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. ... Wikipedia does not yet have an article with this exact name. ...

Two alpha subunits and two beta subunits make up the insulin receptor. The beta subunits pass through the cellular membrane and are linked by disulfide bonds. In chemistry, a disulfide bond is a single covalent bond derived from the coupling of thiol groups. ...

Function

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).

Tyrosine kinase receptors, including the insulin receptor, mediate their activity by causing the addition of a phosphate groups to particular tyrosines on certain proteins within a cell. The "substrate" proteins which are phosphorylated by the Insulin Receptor include a protein called "IRS-1" for "insulin receptor substrate 1". IRS-1 binding and phosphorylation eventually leads to an increase in the high affinity glucose transporter (Glut4) molecules on the outer membrane of insulin-responsive tissues, including muscle cells and adipose tissue, and therefore to an increase in the uptake of glucose from blood into these tissues. Briefly, the glucose transporter (Glut4), is transported from cellular vesicles to the cell surface, where it then can mediate the transport of glucose into the cell. 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. ... Electron micrograph of a section of a liver cell showing glycogen deposits as accumulations of electron dense particles (arrows). ... Glycolysis is a metabolic pathway by which a 6-carbon glucose (Glc) molecule is oxidized to two molecules of pyruvic acid (Pyr). ... 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. ... Wikipedia does not yet have an article with this exact name. ... In chemistry, a phosphate is a polyatomic ion or radical consisting of one phosphorus atom and four oxygen. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... Insulin receptor substrate (IRS) is an important ligand in the insulin response of human cells. ... Insulin receptor substrate (IRS) is an important ligand in the insulin response of human cells. ... To meet Wikipedias quality standards, this article or section may require cleanup. ... To meet Wikipedias quality standards, this article or section may require cleanup. ... A top-down view of skeletal muscle Muscle (from Latin musculus little mouse [1]) is contractile tissue of the body and is derived from the mesodermal layer of embryonic germ cells. ... Adipose tissue is an anatomical term for loose connective tissue composed of energy in the form of fat, although it also cushions and insulates the body. ... Glucose (Glc), a monosaccharide (or simple sugar), is the most important carbohydrate in biology. ...

Pathology

The main activity of activation of the insulin receptor is inducing glucose uptake. For this reason "insulin insensitvity", or a decrease in insulin receptor signaling, leads to diabetes mellitus type 2 - the cells are unable to take up glucose, and the result is hyperglycemia (an increase in circulating glucose), and all the sequelae which result from diabetes. See diabetes mellitus for further general information on diabetes. ...

Patients with insulin resistance may display acanthosis nigricans. 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. ... Acanthosis nigricans is a brown to black, poorly defined, velvety hyperpigmentation of the skin, usually present in the posterior and lateral folds of the neck, the axilla, groin, umbilicus, and other areas. ...

A few patients with homozygous mutations in the INSR gene have been described which causes Donohue Syndrome or Leprechaunism. In most cases the outlook for these patients is poor with death occurring in the first year of life. Donohue Syndrome (also known as Leprechaunism) is an extremely rare medical condition. ...

Regulation of gene expression

The activated IRS-1 acts as a secondary messenger within the cell to stimulate the transcription of insulin-regulated genes. First, the protein Grb2 binds the P-Tyr residue of IRS-1 in its SH2 domain. Grb2 is then able to bind Sos, which in turn catalyzes the replacement of bound GDP with GTP on Ras, a G protein. This protein then begins a phosphorylation cascade, culminating in the activation of mitogen-activated protein kinase (MAPK), which enters the nucleus and phosphorylates various nuclear transcription factors (such as Elk1). Ribbon diagram of the SH2 domain of human P56-Lck tyrosine kinase (PDB accession code 1LKK, chain A), colored from blue (N-terminus) to red (C-terminus). ... G-proteins, short for guanine nucleotide binding proteins, are a family of proteins involved in second messenger cascades. ... In cell biology, mitogen-activated protein kinases (MAPKs) (EC 2. ...

Stimulation of glycogen synthesis

Glycogen synthesis is also stimulated by the insulin receptor via IRS-1. In this case, it is the SH2 domain of PI-3 kinase (PI-3K) that binds the P-Tyr of IRS-1. Now activated, PI-3K can convert the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) to phosphatidylinositol 3,4,5-triphosphate (PIP3). This indirectly activates a protein kinase, PKB, via phosphorylation. PKB then phosphorylates several target proteins, including glycogen synthase kinase 3 (GSK-3). GSK-3 is responsible for phosphorylating (and thus deactivating) glycogen synthase. When GSK-3 is phosphorylated, it is deactivated, and prevented from deactivating glycogen synthase. In this roundabout manner, insulin increases glycogen synthesis. Ribbon diagram of the SH2 domain of human P56-Lck tyrosine kinase (PDB accession code 1LKK, chain A), colored from blue (N-terminus) to red (C-terminus). ... Glycogen Synthase Kinase 3 (GSK-3) is a serine/threonine protein kinase. ... Glycogen Synthase Kinase 3 (GSK-3) is a serine/threonine protein kinase. ... Glycogen Synthase Kinase 3 (GSK-3) is a serine/threonine protein kinase. ...

External links

• MeSH Insulin+receptor