Essential role of protein kinase Cζ in the impairment of insulin-induced glucose transport in IRS-2-deficient brown adipocytes
- 22 January 2003
- journal article
- Published by Wiley in FEBS Letters
- Vol. 536 (1) , 161-166
- https://doi.org/10.1016/s0014-5793(03)00049-8
Abstract
Insulin receptor substrate-2-deficient (IRS-2-/-) mice develop type 2 diabetes. We have investigated the molecular mechanisms by which IRS-2-/- immortalized brown adipocytes showed an impaired response to insulin in inducing GLUT4 translocation and glucose uptake. IRS-2-associated phosphatidylinositol 3-kinase (PI 3-kinase) activity was blunted in IRS-2-/- cells, total PI 3-kinase activity being reduced by 30%. Downstream, activation of protein kinase C (PKC) ζ was abolished in IRS-2-/- cells. Reconstitution with retroviral IRS-2 restores IRS-2/PI 3-kinase/PKCζ signalling, as well as glucose uptake. Wild-type cells expressing a kinase-inactive mutant of PKCζ lack GLUT4 translocation and glucose uptake. Our results support the essential role played by PKCζ in the insulin resistance and impaired glucose uptake observed in IRS-2-deficient brown adipocytes.This work was supported by Grant SAF2001/1302 from M.C.T., Spain.Peer RevieweKeywords
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