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Permissive action of protein kinase C-zeta in insulin-induced CD36- and GLUT4 translocation in cardiac myocytes.

Authors: Luiken, JJ  Ouwens, DM  Habets, DD  Van der Zon, GC  Coumans, WA  Schwenk, RW  Bonen, A  Glatz, JF 
Citation: Luiken JJ, etal., J Endocrinol. 2009 May;201(2):199-209. Epub 2009 Mar 9.
Pubmed: (View Article at PubMed) PMID:19273501
DOI: Full-text: DOI:10.1677/JOE-09-0046

Insulin stimulates cardiac long-chain fatty acid (LCFA) and glucose uptake via translocation of human homolog of rat fatty acid translocase (CD36) and GLUT4 respectively, from intracellular membrane compartments to the sarcolemma, a process dependent on the activation of phosphatidylinositol-3 kinase. To identify downstream kinases of insulin signaling involved in translocation of CD36 and GLUT4 in the heart, we tested i) which cardiac protein kinase C (PKC) isoforms (alpha, delta, epsilon or zeta) are activated by insulin, and ii) whether PKC isoform-specific inhibition affects insulin-stimulated substrate uptake in the heart. Insulin-stimulated LCFA and glucose uptake were completely blunted by inhibition of PKC-zeta, but not by inhibition of conventional or novel PKCs. Concomitantly, translocation of CD36 and GLUT4 to the sarcolemma was completely blunted upon inhibition of PKC-zeta. However, insulin, in contrast to the diacylglycerol-analog phorbol-12-myristate-13-acetate (PMA), did not induce membrane-attachment of the conventional and novel PKCs-alpha, -delta, and -epsilon. PKC-zeta was already entirely membrane-bound in non-stimulated cells, and neither insulin nor PMA treatment had any effect on the subcellular localization of PKC-zeta. Furthermore, insulin treatment did not change phosphorylation of PKC-alpha, -delta, and -zeta or enzymatic activity of PKC-zeta towards a PKC-zeta substrate peptide. It is concluded that PKC-zeta, but not any other PKC isoform, is necessary for insulin-induced translocation of GLUT4 and CD36. However, PKC-zeta is already fully active under basal conditions and not further activated by insulin, indicating that its role in insulin-stimulated uptake of both glucose and LCFA is permissive rather than regulatory.


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CRRD Object Information
CRRD ID: 2307221
Created: 2009-05-22
Species: All species
Last Modified: 2009-05-22
Status: ACTIVE


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