HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: JOE-09-0046v1 201/2/199    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Luiken, J. J F P Articles by Glatz, J. F C Search for Related Content PubMed PubMed Citation Articles by Luiken, J. J F P Articles by Glatz, J. F C

Department of Molecular Genetics, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, PO Box 616, NL-6200 MD Maastricht, The Netherlands¹ Department of Molecular Cell Biology, Leiden University Medical Center, PO Box 9600, NL-2300 RC Leiden, The Netherlands² Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada N1G 2W1

(Correspondence should be addressed to J J F P Luiken; Email: j.luiken{at}gen.unimaas.nl)

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 (, , or ) 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-, 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-. 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-, -, and -. PKC- was already entirely membrane-bound in non-stimulated cells, and neither insulin nor PMA treatment had any effect on the subcellular localization of PKC-. Furthermore, insulin treatment did not change phosphorylation of PKC-, -, and - or enzymatic activity of PKC- towards a PKC- substrate peptide. It is concluded that PKC-, but not any other PKC isoform, is necessary for insulin-induced translocation of GLUT4 and CD36. However, PKC- 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.

This article has been cited by other articles:

				J. F. C. Glatz, J. J. F. P. Luiken, and A. Bonen Membrane Fatty Acid Transporters as Regulators of Lipid Metabolism: Implications for Metabolic Disease Physiol Rev, January 1, 2010; 90(1): 367 - 417. [Abstract] [Full Text] [PDF]