Insulin Induced Actin Remodeling GluT4 Translocation and Caveolae

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Adipocytes are terminally differentiated and are not dividing. They are also not migrating or spreading on the extracellular matrix, and they do not have well-formed stress fibers. Therefore, what is the significance of caveolin phosphorylation and Csk-induced attenuation of Src-family kinase activity in response to insulin in these cells? Insulin increases glucose transport in fat and muscle cells by stimulating the translocation of GluT4 from intracellular vesicles to the plasma membrane. Insulin induces cortical actin remodeling which is required for Glut4 translocation [116,117]. Therefore, the regulation of cortical actin assembly is a key process in the stimulation of glucose transport by insulin. In a manner analogous to cell migration, cortical actin remodeling would require that the tension between the cell surface and the actin cytoskeleton first be transiently relieved, followed by rapid formation of new initiation sites for actin assembly at the membrane. Based on other modes of actin remodeling, it is likely that Src-family kinases and Csk play roles in insulin-induced actin remodeling in adipocytes.

In adipocytes, caveolin is co-localized with actin in unique complexes at the cell surface [118,119]. Disruption of these complexes, either through expression of dominant-negative forms of caveolin or by treatment with cyclodextran, blocks insulin-stimulated cortical actin assembly and GluT4 translocation [120]. Insulin-stimulated caveolin phosphorylation would activate Csk close to sites of cortical actin assembly, which would modulate the insulin-induced actin remodeling. Consistent with this, other stimuli that induce GluT4 translocation also stimulate caveolin phosphorylation, including endothelin-1, angiotensin II, and osmotic stress [14,15,18,28,32].

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Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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