TY - JOUR

T1 - Involvement of atypical protein kinase C in the regulation of cardiac glucose and long-chain fatty acid uptake

AU - Habets, Daphna D J

AU - Luiken, Joost J F P

AU - Ouwens, Margriet

AU - Coumans, Will A

AU - Vergouwe, Monique

AU - Maarbjerg, Stine Just

AU - Leitges, Michael

AU - Bonen, Arend

AU - Richter, Erik A.

AU - Glatz, Jan F C

N1 - CURIS 2012 5200 139

PY - 2012

Y1 - 2012

N2 - 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-¿ knockout mice the roles of atypical PKCs (PKC-¿ and PKC-¿) 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-¿ ablation in cardiomyocytes. In contrast, myristoylated PKC-¿ pseudosubstrate inhibited both insulin-stimulated and AMPK-mediated glucose and fatty acid uptake by >80% in both wild-type and PKC-¿-knockout cardiomyocytes. In PKC-¿ knockout cardiomyocytes, PKC-¿ 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-¿ activity in PKC-¿-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-¿ and PKC-¿ have interchangeable functions in these processes.

AB - 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-¿ knockout mice the roles of atypical PKCs (PKC-¿ and PKC-¿) 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-¿ ablation in cardiomyocytes. In contrast, myristoylated PKC-¿ pseudosubstrate inhibited both insulin-stimulated and AMPK-mediated glucose and fatty acid uptake by >80% in both wild-type and PKC-¿-knockout cardiomyocytes. In PKC-¿ knockout cardiomyocytes, PKC-¿ 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-¿ activity in PKC-¿-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-¿ and PKC-¿ have interchangeable functions in these processes.

U2 - 10.3389/fphys.2012.00361

DO - 10.3389/fphys.2012.00361

M3 - Journal article

C2 - 22973240

VL - 3

SP - 361

JO - Frontiers in Physiology

JF - Frontiers in Physiology

SN - 1664-042X

ER -