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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/30127

Title: Characterizing the Role of a Novel F-actin Binding Protein in IRS1/PI3K Signaling and Glucose Uptake
Authors: Lee, Andrew
Advisor: Rozakis-Adcock, Maria
Department: Laboratory Medicine and Pathobiology
Keywords: type 2 diabetes
insulin resistance
Issue Date: 30-Nov-2011
Abstract: Studies show that insulin induced activation and assembly of insulin receptor substrate-1 (IRS1) and phosphatidylinositol-3-kinase (PI3K), within remodelled actin structures is critical for GLUT4 translocation to the cell surface in muscle cells. This study identifies the F-actin binding protein, nexilin, as a novel IRS1 binding partner. Insulin stimulates nexilin to dissociate from IRS1 and interact with actin. Nexilin knockdown has no effect on insulin-stimulated IRS1 tyrosine phosphorylation, but does enhance insulin-stimulated IRS1-PI3K interaction, increasing PIP3 formation, PKB activation and glucose uptake. This study also shows that nexilin overexpression may have an inhibitory effect on PKB phosphorylation and glucose uptake in adipocytes. These findings suggest nexilin is a negative regulator of IRS1 action on PI3K and insulin-stimulated dissociation of IRS1-nexilin allows the formation of IRS1-PI3K complexes in cytoskeletal-membrane compartments. Nexilin also specifically associates with the PH domain of IRS1, and not IRS2, suggesting a mechanism for signaling specificity of these isoforms.
URI: http://hdl.handle.net/1807/30127
Appears in Collections:Master

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