Involvement of atypical protein kinase C in the regulation of cardiac glucose and long-chain fatty acid uptake
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Involvement of atypical protein kinase C in the regulation of cardiac glucose and long-chain fatty acid uptake. / Habets, Daphna D J; Luiken, Joost J F P; Ouwens, Margriet; Coumans, Will A; Vergouwe, Monique; Maarbjerg, Stine Just; Leitges, Michael; Bonen, Arend; Richter, Erik A.; Glatz, Jan F C.
I: Frontiers in Physiology, Bind 3, 2012, s. 361.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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 -
ID: 41813098