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PKClambda in liver mediates insulin-induced SREBP-1c expression and determines both hepatic lipid content and overall insulin sensitivity.

Authors: Matsumoto, M  Ogawa, W  Akimoto, K  Inoue, H  Miyake, K  Furukawa, K  Hayashi, Y  Iguchi, H  Matsuki, Y  Hiramatsu, R  Shimano, H  Yamada, N  Ohno, S  Kasuga, M  Noda, T 
Citation: Matsumoto M, etal., J Clin Invest. 2003 Sep;112(6):935-44.
Pubmed: (View Article at PubMed) PMID:12975478
DOI: Full-text: DOI:10.1172/JCI18816

PKClambda is implicated as a downstream effector of PI3K in insulin action. We show here that mice that lack PKClambda specifically in the liver (L-lambdaKO mice), produced with the use of the Cre-loxP system, exhibit increased insulin sensitivity as well as a decreased triglyceride content and reduced expression of the sterol regulatory element-binding protein-1c (SREBP-1c) gene in the liver. Induction of the hepatic expression of Srebp1c and of its target genes involved in fatty acid/triglyceride synthesis by fasting and refeeding or by hepatic expression of an active form of PI3K was inhibited in L-lambdaKO mice compared with that in control animals. Expression of Srebp1c induced by insulin or by active PI3K in primary cultured rat hepatocytes was inhibited by a dominant-negative form of PKClambda and was mimicked by overexpression of WT PKClambda. Restoration of PKClambda expression in the liver of L-lambdaKO mice with the use of adenovirus-mediated gene transfer corrected the metabolic abnormalities of these animals. Hepatic PKClambda is thus a determinant of hepatic lipid content and whole-body insulin sensitivity.

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CRRD Object Information
CRRD ID: 2314946
Created: 2009-12-09
Species: All species
Last Modified: 2009-12-09
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.