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Munc18c is not rate-limiting for glucose and long-chain fatty acid uptake in the heart

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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 5′ AMP-activated protein kinase-activating agent)-stimulated glucose and LCFA uptake were not altered significantly 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.

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Abbreviations

ACC:

Acetyl-CoA carboxylase

AMPK:

5′ AMP-activated protein kinase

CD36:

Fatty acid translocase

GAPDH:

Glyceraldehydes-3-phosphate dehydrogenase

GLUT4:

Glucose transporter-4

LCFA:

Long-chain fatty acids

PKB:

Protein kinase-B

SNAP23:

Soluble NSF-attachment protein-23

t/vSNARE:

Target/vesicular soluble N-ethylmaleimide-sensitive factor-attachment protein receptor

VAMP2:

Vesicle-associated membrane protein-2

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Acknowledgments

This study was supported by the Netherlands Organisation for Health Research and Development (ZonMw grant nr. 40-00812-98-03075), the European Community (Integrated Project LSHM-CT-2004-005272, Exgenesis), the National Institutes of Health (DK67912 to D.C.T.), and the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada, the Heart and Stroke Foundation of Ontario, the Canada Research Chair program. A. Bonen is the Canada Research Chair in Metabolism and Health. J. F. C. Glatz is Netherlands Heart Foundation Professor of Cardiac Metabolism.

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Correspondence to Daphna D. J. Habets.

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Habets, D.D.J., Thurmond, D.C., Coumans, W.A. et al. Munc18c is not rate-limiting for glucose and long-chain fatty acid uptake in the heart. Mol Cell Biochem 322, 81–86 (2009). https://doi.org/10.1007/s11010-008-9942-y

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  • DOI: https://doi.org/10.1007/s11010-008-9942-y

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