Editing Insulin receptor (section)

== Function ==

=== 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|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 [[Phosphoinositide 3-kinase|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|phosphatidylinositol 4,5-bisphosphate]] (PIP<sub>2</sub>) to [[Phosphatidylinositol (3,4,5)-trisphosphate|phosphatidylinositol 3,4,5-triphosphate]] (PIP<sub>3</sub>).  This indirectly activates a protein kinase, PKB ([[Akt]]), 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.<ref name="pmid9793760">{{cite journal | vauthors = Duckworth WC, Bennett RG, Hamel FG | title = Insulin degradation: progress and potential | journal = Endocrine Reviews | volume = 19 | issue = 5 | pages = 608–24 | date = October 1998 | pmid = 9793760 | doi = 10.1210/edrv.19.5.0349 | doi-access = free }}</ref>

=== Immune system ===
Besides the metabolic function, insulin receptors are also expressed on immune cells, such as macrophages, B cells, and T cells. On T cells, the expression of insulin receptors is undetectable during the resting state but up-regulated upon [[T-cell receptor]] (TCR) activation. Indeed, [[insulin]] has been shown when supplied exogenously to promote ''in vitro'' T cell proliferation in animal models. Insulin receptor signalling is important for maximizing the potential effect of T cells during acute infection and inflammation.<ref>{{cite journal | vauthors = Tsai S, Clemente-Casares X, Zhou AC, Lei H, Ahn JJ, Chan YT, Choi O, Luck H, Woo M, Dunn SE, Engleman EG, Watts TH, Winer S, Winer DA | display-authors = 6 | title = Insulin Receptor-Mediated Stimulation Boosts T Cell Immunity during Inflammation and Infection | journal = Cell Metabolism | volume = 28 | issue = 6 | pages = 922–934.e4 | date = August 2018 | pmid = 30174303 | doi = 10.1016/j.cmet.2018.08.003 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Fischer HJ, Sie C, Schumann E, Witte AK, Dressel R, van den Brandt J, Reichardt HM | title = The Insulin Receptor Plays a Critical Role in T Cell Function and Adaptive Immunity | journal = Journal of Immunology | volume = 198 | issue = 5 | pages = 1910–1920 | date = March 2017 | pmid = 28115529 | doi = 10.4049/jimmunol.1601011 | doi-access = free }}</ref>