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Insulin receptor

Insulin receptor
PDB rendering based on 1gag.
Available structures: 1gag, 1i44, 1ir3, 1irk, 1p14, 1rqq, 2auh, 2b4s, 2dtg, 2hr7
Symbol(s) INSR; CD220; HHF5
External IDs OMIM: 147670 MGI: 96575 Homologene: 20090
RNA expression pattern

More reference expression data

Human Mouse
Entrez 3643 16337
Ensembl ENSG00000171105 ENSMUSG00000005534
Uniprot P06213 O35466
Refseq NM_000208 (mRNA)
NP_000199 (protein)
XM_972939 (mRNA)
XP_978033 (protein)
Location Chr 19: 7.07 - 7.25 Mb Chr 8: 3.16 - 3.28 Mb
Pubmed search [1] [2]

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.

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.



  Tyrosine kinase receptors, including the insulin receptor, mediate their activity by causing the addition of a phosphate group 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.


The main activity of activation of the insulin receptor is inducing glucose uptake. For this reason "insulin insensitivity", 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.

Patients with insulin resistance may display acanthosis nigricans.

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.

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).

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.

Degradation of insulin

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 is finally degraded about 71 minutes after its initial release into circulation.[1]


  1. ^ William C. Duckworth, Robert G. Bennett and Frederick G. Hamel (1998). Insulin Degradation: Progress and Potential, Endocrine Reviews 19 (5): 608-624.

Further reading

  • Pearson RB, Kemp BE (1991). "Protein kinase phosphorylation site sequences and consensus specificity motifs: tabulations.". Meth. Enzymol. 200: 62-81. PMID 1956339.
  • Joost HG (1995). "Structural and functional heterogeneity of insulin receptors.". Cell. Signal. 7 (2): 85-91. PMID 7794689.
  • O'Dell SD, Day IN (1998). "Insulin-like growth factor II (IGF-II).". Int. J. Biochem. Cell Biol. 30 (7): 767-71. PMID 9722981.
  • Lopaczynski W (1999). "Differential regulation of signaling pathways for insulin and insulin-like growth factor I.". Acta Biochim. Pol. 46 (1): 51-60. PMID 10453981.
  • Sasaoka T, Kobayashi M (2000). "The functional significance of Shc in insulin signaling as a substrate of the insulin receptor.". Endocr. J. 47 (4): 373-81. PMID 11075717.
  • Perz M, Torlińska T (2001). "Insulin receptor--structural and functional characteristics.". Med. Sci. Monit. 7 (1): 169-77. PMID 11208515.
  • Benaim G, Villalobo A (2002). "Phosphorylation of calmodulin. Functional implications.". Eur. J. Biochem. 269 (15): 3619-31. PMID 12153558.
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Insulin_receptor". A list of authors is available in Wikipedia.
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