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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Daphna D J Habets
  • Joost J F P Luiken
  • Margriet Ouwens
  • Will A Coumans
  • Monique Vergouwe
  • Stine Just Maarbjerg
  • Michael Leitges
  • Arend Bonen
  • Richter, Erik A.
  • Jan F C Glatz
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.
OriginalsprogEngelsk
TidsskriftFrontiers in Physiology
Vol/bind3
Sider (fra-til)361
Antal sider8
ISSN1664-042X
DOI
StatusUdgivet - 2012

Bibliografisk note

CURIS 2012 5200 139

ID: 41813098