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Mol Cell Biochem (2009) 322:8186 DOI 10.1007/s11010-008-9942-y
Munc18c is not rate-limiting for glucose and long-chain fatty acid uptake in the heart
Daphna D. J. Habets Debbie C. Thurmond Will A. Coumans Arend Bonen Jan F. C. Glatz Joost J. F. P. Luiken
Received: 5 August 2008 / Accepted: 22 October 2008 / Published online: 14 November 2008 Springer Science+Business Media, LLC. 2008
Abstract The role of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)- and SNARE-associated proteins have not yet been assessed in regulation of cardiac glucose uptake, nor in the regulation of long-chain fatty acid (LCFA) uptake in any tissue. Munc18c is a SNARE-associated protein that regulates GLUT4 translocation in skeletal muscle and adipose tissue. Using cardiomyocytes from Munc18c-/? mice (with 56% reduction of Munc18c protein expression), we investigated whether this syntaxin4-associated protein is involved in regulation of cardiac substrate uptake. Basal, insulin- and oligomycin (a 50 AMP-activated protein kinase-activating agent)-stimulated glucose and LCFA uptake were not altered signicantly in Munc18c-/? cardiomyocytes compared to wild-type cells. We conclude, therefore, that Munc18c is not rate-limiting for cardiac substrate uptake, neither under basal conditions nor when maximally stimulated metabolically.
Keywords Munc18c Long-chain fatty acid uptake
Glucose uptake Cardiomyocytes
AbbreviationsACC Acetyl-CoA carboxylase AMPK 50 AMP-activated protein kinase
CD36 Fatty acid translocaseGAPDH Glyceraldehydes-3-phosphate dehydrogenase GLUT4 Glucose transporter-4LCFA Long-chain fatty acidsPKB Protein kinase-BSNAP23 Soluble NSF-attachment protein-23 t/vSNARE Target/vesicular soluble N-ethylmaleimide-sensitive factor-attachment protein receptor VAMP2 Vesicle-associated membrane protein-2
Introduction
In the heart, long-chain fatty acids (LCFA) and glucose are the predominant substrates. Glucose is mainly taken up into cardiomyocytes via glucose transporter-4 (GLUT4), and LCFA largely via fatty acid translocase (CD36) [1]. Both transporters recycle between intracellular stores and the sarcolemma, and can be induced to translocate to the sarcolemma by several physiological stimuli, such as an increase in circulating concentrations of insulin [2], and an increase in contractile activity [3]. Hence, both the translocation of GLUT4 and CD36 appear to be similarly regulated. This similarity also applies to the signaling components activated by each of these stimuli. Insulin recruits both GLUT4 and CD36 via activation of the phosphatidylinositol-3-kinaseAkt/protein kinase B (PKB) axis, and contraction recruits these transporters via activation of the LKB150
AMP-activated protein kinase (AMPK) axis [2, 3].
The translocation of GLUT4 and CD36 to the sarco-lemma in response...