title: Involvement of atypical protein kinase C in the regulation of cardiac glucose and long-chain fatty acid uptake.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Molecular Genetics, Cardiovascular Research Institute Maastricht, Maastricht University Maastricht, Netherlands.
authors.forename: Daphna D J
authors.initials: DD
authors.lastname: Habets
authors.forename: Joost J F P
authors.initials: JJ
authors.lastname: Luiken
authors.forename: Margriet
authors.initials: M
authors.lastname: Ouwens
authors.forename: Will A
authors.initials: WA
authors.lastname: Coumans
authors.forename: Monique
authors.initials: M
authors.lastname: Vergouwe
authors.forename: Stine J
authors.initials: SJ
authors.lastname: Maarbjerg
authors.forename: Michael
authors.initials: M
authors.lastname: Leitges
authors.forename: Arend
authors.initials: A
authors.lastname: Bonen
authors.forename: Erik A
authors.initials: EA
authors.lastname: Richter
authors.forename: Jan F C
authors.initials: JF
authors.lastname: Glatz