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Habets DD, Luiken JJ, Ouwens M, et al. Involvement of atypical protein kinase C in the regulation of cardiac glucose and long-chain fatty acid uptake. Front Physiol. 2012;3:361doi: 10.3389/fphys.2012.00361.
Habets, D. D., Luiken, J. J., Ouwens, M., Coumans, W. A., Vergouwe, M., Maarbjerg, S. J., Leitges, M., Bonen, A., Richter, E. A., & Glatz, J. F. (2012). Involvement of atypical protein kinase C in the regulation of cardiac glucose and long-chain fatty acid uptake. Frontiers in physiology, 3361. https://doi.org/10.3389/fphys.2012.00361
Habets, Daphna D J, et al. "Involvement of atypical protein kinase C in the regulation of cardiac glucose and long-chain fatty acid uptake." Frontiers in physiology vol. 3 (2012): 361. doi: https://doi.org/10.3389/fphys.2012.00361
Habets DD, Luiken JJ, Ouwens M, Coumans WA, Vergouwe M, Maarbjerg SJ, Leitges M, Bonen A, Richter EA, Glatz JF. Involvement of atypical protein kinase C in the regulation of cardiac glucose and long-chain fatty acid uptake. Front Physiol. 2012 Sep 11;3:361. doi: 10.3389/fphys.2012.00361. eCollection 2012. PMID: 22973240; PMCID: PMC3438470.
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Front Physiol. 2012 Sep 11;3:361. doi: 10.3389/fphys.2012.00361. eCollection 2012.

Involvement of atypical protein kinase C in the regulation of cardiac glucose and long-chain fatty acid uptake.

Frontiers in physiology

Daphna D J Habets, Joost J F P Luiken, Margriet Ouwens, Will A Coumans, Monique Vergouwe, Stine J Maarbjerg, Michael Leitges, Arend Bonen, Erik A Richter, Jan F C Glatz

Affiliations

  1. Department of Molecular Genetics, Cardiovascular Research Institute Maastricht, Maastricht University Maastricht, Netherlands.

PMID: 22973240 PMCID: PMC3438470 DOI: 10.3389/fphys.2012.00361

Abstract

AIM: The signaling pathways involved in the regulation of cardiac GLUT4 translocation/glucose uptake and CD36 translocation/long-chain fatty acid uptake are not fully understood. We compared in heart/muscle-specific PKC-λ knockout mice the roles of atypical PKCs (PKC-ζ and PKC-λ) in regulating cardiac glucose and fatty acid uptake.

RESULTS: Neither insulin-stimulated nor AMPK-mediated glucose and fatty acid uptake were inhibited upon genetic PKC-λ ablation in cardiomyocytes. In contrast, myristoylated PKC-ζ pseudosubstrate inhibited both insulin-stimulated and AMPK-mediated glucose and fatty acid uptake by >80% in both wild-type and PKC-λ-knockout cardiomyocytes. In PKC-λ knockout cardiomyocytes, PKC-ζ is the sole remaining atypical PKC isoform, and its expression level is not different from wild-type cardiomyocytes, in which it contributes to 29% and 17% of total atypical PKC expression and phosphorylation, respectively.

CONCLUSION: Taken together, atypical PKCs are necessary for insulin-stimulated and AMPK-mediated glucose uptake into the heart, as well as for insulin-stimulated and AMPK-mediated fatty acid uptake. However, the residual PKC-ζ activity in PKC-λ-knockout cardiomyocytes is sufficient to allow optimal stimulation of glucose and fatty acid uptake, indicating that atypical PKCs are necessary but not rate-limiting in the regulation of cardiac substrate uptake and that PKC-λ and PKC-ζ have interchangeable functions in these processes.

Keywords: AMPK; atypical PKCs; cardiomyocytes; glucose uptake; insulin; long-chain fatty acid uptake

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