The insulin receptor is specific plasma membrane receptor with tyrosine kinase activity (13), to which insulin is bound. This kinase activates the insulin receptor substrate (IRS) proteins on multiple sites; these IRS proteins serve as binding scaffolds for a variety of adaptor proteins and lead to the downstream signaling cascade (Fig. 4) (14). Insulin activates a series of lipid and protein kinase enzymes linked to the translocation of glucose transporters to the cell surface, synthesis of glycogen, protein, mRNAs and to nuclear DNA that influences cell survival and proliferation. Insulin resistance presumably results from mechanisms blocking insulin signaling. It is of note that various normal biological processes can inhibit IRS protein activity via phosphorylation at specific serine and threonine residues within the IRS proteins. Other processes can interfere with insulin signaling by interfering with other proteins further
Tissue-specific Knockout Insulin Receptor
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