Fig. 1.   Insulin release and action. Glucose enters beta cells via the glucose transporter (GLUT2) and ATP is generated by glycolysis. This results in closure of ATP-sensitive K⁺ channels, depolarization of the plasma membrane, and opening of voltage-dependent Ca²⁺ channels. The influx of Ca²⁺ leads to the release of insulin (1), which is carried in the bloodstream to cells throughout the body where it binds to insulin receptors. This results in autophosphorylation of insulin receptors and phosphorylation of tyrosines on a variety of cellular proteins including members of the insulin receptor substrate (IRS) family and Cbl-CAP (2). The phosphorylated proteins provide docking sites for SH2 domains of several proteins (e.g. phosphatidylinositol 3-kinase (PI(3)K); Grb2 and SHP2; and Crk) that activate different signaling pathways (dashed lines). This results in translocation of the glucose transporter (GLUT4) and uptake of glucose by the cell; alterations in glucose, lipid, and protein metabolism; and changes in gene expression and cell growth.

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