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IRS-3 mediates insulin-induced glucose uptake in differentiated IRS-2-/- brown adipocytes

AuthorsEscribano, Óscar; Arribas, Mónica; Valverde, Ángela M.; Benito, Manuel
KeywordsBrown adipocyte
IRSs proteins
Insulin-induced glucose transport
Glucose uptake
Issue Date2007
CitationMolecular and Cellular Endocrinology 268(1-2): 1-9 (2007)
AbstractIRS-2 mediates insulin-induced glucose uptake in brown preadipocytes. Upon differentiation, basal IRS-3 expression increased concurrently with an enhancement in the IRS-3-associated phosphatidylinositol (PI) 3-kinase activity in the Triton-insoluble fraction in wild-type and IRS-2-deficient brown adipocytes stimulated with insulin. Moreover, insulin induced protein kinase B (Akt) and protein kinase C (PKC) ζ phosphorylation in both kinds of cells. More importantly, insulin induced glucose uptake in differentiated IRS-2-deficient brown adipocytes in a wortmannin-dependent manner. However, while insulin induced Akt phosphorylation occurred mainly in the cytosolic fraction, PKC ζ activation was constrained to the Triton-insoluble fraction. The reduction of IRS-3 expression by siRNA inhibited insulin-induced glucose uptake and also PKC ζ activation in differentiated IRS-2−/− brown adipocytes. In addition, inhibition of PKC ζ totally blunted insulin-induced glucose uptake in those cells. Our results provide evidences suggesting that IRS-3/PI 3-kinase/PKC ζ signaling is the main responsible for the insulin-induced glucose uptake observed upon differentiation of brown adipocytes lacking IRS-2.
Identifiersdoi: 10.1016/j.mce.2006.12.039
issn: 0303-7207
e-issn: 1872-8057
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