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Pathways of insulin signaling. The binding of insulin to its plasma membrane receptor activates a cascade of downstream signaling events. Insulin binding
activates the intrinsic tyrosine kinase activity of the receptor dimer, resulting in the tyrosine phosphorylation (Y-P) of the receptor's β subunits and a small
number of specific substrates (yellow shapes): the Insulin Receptor Substrate (IRS) proteins, Gab-1 and SHC; within the membrane, a caveolar pool of
insulin receptor phosphorylates caveolin (Cav), APS, and Cbl. These tyrosine-phosphorylated proteins interact with signaling cascades via SH2 and SH3
domains to mediate the effects of insulin, with specific effects resulting from each pathway. In target tissues such as skeletal muscle and adipocytes, a key
event is the translocation of the Glut4 glucose transporter from intracellular vesicles to the plasma membrane; this translocation is stimulated by both the
Source: Endocrine Pancreas and Pharmacotherapy of Diabetes Mellitus and Hypoglycemia, Goodman & Gilman's: The Pharmacological Basis
caveolar and non-caveolar pathways. In the non-caveolar pathway, the activation of PI3K is crucial, and PKB/Akt (anchored at the membrane by PIP3)
of Therapeutics, 12e
and/or an atypical form of PKC is involved. In the caveolar pathway, caveolar protein flotillin localizes the signaling complex to the caveola; the signaling
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binding protein, TC10. The pathways are inactivated by specific phosphoprotein phosphatases (eg, PTB1B). In addition to the actions shown, insulin also
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2017 McGraw-Hill
Education.
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stimulates the
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