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

• Main Authors: Daphna D.J. Habets, Joost J.F.P. Luiken, Margriet eOuwens, Will A. Coumans, Monique eVergouwe, Stine J. Maarbjerg, Michael eLeitges, Arend eBonen, Erik A. Richter, Jan eGlatz
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2012-09-01
• Series: Frontiers in Physiology
• Subjects: Insulin; cardiomyocytes; AMPK; CD36; atypical PKC; fatty acid uptake
• Online Access: http://journal.frontiersin.org/Journal/10.3389/fphys.2012.00361/full

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.