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(https://www.bocsci.com/insulin-signaling-pathway.html)

Insulin signaling in diseases

(1) The Diabetes mellitus

The normal operation of the insulin signal pathways plays an important role in insulin physiological function. The disorder of insulin signal transduction will weak the physiological action of insulin, leading to insulin resistance and type 2 diabetes mellitus. Insulin resistance refers to the decrease in insulin utilization rate and insulin sensitivity caused by various reasons, which is the main pathological basis of type 2 diabetes. Current research suggests that the main cause of insulin resistance is the elevated levels of inflammatory cytokines, which interfere with the normal phosphorylation of IRS in the insulin signal transduction, blocking a series of cascade amplification reaction activated by the downstream signal, andthus affect the physiological function of insulin, such as generation, transportation, leading insulin resistance. The insulin signal enters cell and triggers a serial biochemical reaction through the insulin receptor (IR). Emerging knowledge of insulin pathway and pathogenic mechanisms has led to a host of new molecular drug targets mainly involved in improving the insulin sensitivity of target cells and promoting uptake and utilization of glucose. A key role of insulin is to stimulate glucose uptake into cells by inducing GLUT4, the translocation of the glucose transporter. When insulin is lacking, constitutively activated mutants of PI3-kinase and PKB overexpress and stimulate the recruitment of GLUT4 to the cell surface. Recently, some studies suggest that another PI3-kinase independent pathway may provide a second signal that plays an important role in allowing insulin to stimulate the recruitment of GLUT4 to the cell membrane. In this pathway, activated insulin receptor phosphorylates the proto-oncogene Cbl directly to activate the TC10 family of Rho GTP-binding proteins. Then these proteins interact with unknown effector proteins to allow translocation of insulin-stimulated GLUT4.