Essential role of protein kinase Cζ in the impairment of insulin-induced glucose transport in IRS-2-deficient brown adipocytes

被引：18

作者：

Arribas, M

Valverde, AM

Burks, D

Klein, J

Farese, RV

White, MF

Benito, M ^{[1
]}

机构：

[1] Univ Complutense, Fac Farm, CSIC, Ctr Mixto,Inst Bioquim,Dept Bioquim & Biol Mol, E-28040 Madrid, Spain

[2] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA

[3] Univ S Florida, Coll Med, Dept Internal Med, Tampa, FL 33612 USA

[4] Med Univ Lubeck, Dept Internal Med 1, D-23538 Lubeck, Germany

[5] Fac Med, Dept Anat, Salamanca 37007, Spain

来源：

FEBS LETTERS | 2003年 / 536卷 / 1-3期

关键词：

protein kinase C; insulin receptor substrate-2; glucose transport;

D O I：

10.1016/S0014-5793(03)00049-8

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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) zeta was abolished in IRS-2(-/-) cells. Reconstitution with retroviral IRS-2 restores IRS-2/PI 3-kinase/PKCzeta signalling, as well as glucose uptake. Wild-type cells expressing a kinase-inactive mutant of PKCzeta lack GLUT4 translocation and glucose uptake. Our results support the essential role played by PKCzeta in the insulin resistance and impaired glucose uptake observed in IRS-2-deficient brown adipocytes. (C) 2003 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.

引用

页码：161 / 166

页数：6

共 29 条

[1] PHOSPHATIDYLINOSITOL 3'-KINASE IS ACTIVATED BY ASSOCIATION WITH IRS-1 DURING INSULIN STIMULATION [J].