NDLI: Insulin signaling through Akt/protein kinase B analyzed by small interfering RNA-mediated gene silencing.

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Insulin signaling through Akt/protein kinase B analyzed by small interfering RNA-mediated gene silencing.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Zhou, Qiong L. Jiang, Zhen Y. Coleman, Kerri A. Czech, Michael P. Boese, Queta Chouinard, My
Description	Author Affiliation: Jiang ZY ( Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA.);
Abstract	Glucose homeostasis is controlled by insulin in part through the translocation of intracellular glucose transporter 4 to the plasma membrane in muscle and fat cells. Akt/protein kinase B downstream of phosphatidylinositol 3-kinase has been implicated in this insulin-signaling pathway, but results with a variety of reagents including Akt1-/- and Akt2-/- mice have been equivocal. Here we report the application of small interfering RNA-directed gene silencing to deplete both Akt1 and Akt2 in cultured 3T3-L1 adipocytes. Loss of Akt1 alone slightly impaired insulin-mediated hexose transport activity but had no detectable effect on glycogen synthase kinase (GSK)-3 phosphorylation. In contrast, depletion of Akt2 alone by 70% inhibited approximately half of the insulin responsiveness. Combined depletions of Akt1 plus Akt2 in these cells even more markedly attenuated insulin action on glucose transporter 4 movements, hexose transport activity, and GSK-3 phosphorylation. These data demonstrate a primary role of Akt2 in insulin signaling, significant functional redundancy of Akt1 and Akt2 isoforms in this pathway, and an absolute requirement of Akt protein kinases for regulation of glucose transport and GSK-3 in cultured adipocytes.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	13
Volume Number	100
Language	English
Publisher	National Academy of Sciences
Publisher Date	2003-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Gene Silencing Insulin Metabolism Proto-Oncogene Proteins RNA, Small Interfering Signal Transduction 3T3 Cells Adipocytes Animals Biological Transport Blotting, Western Cells, Cultured Deoxyglucose Pharmacokinetics Electroporation Fibroblasts Glucose Mice Microscopy, Fluorescence Phosphatidylinositol 3-Kinases Phosphorylation Plasmids Protein-Serine-Threonine Kinases Proto-Oncogene Proteins C-akt Time Factors Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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