Contraction stimulates muscle glucose uptake independent of atypical PKC

Exercise increases skeletal muscle glucose uptake, but the underlying mechanisms are only partially understood. The atypical protein kinase C (PKC) isoforms λ and ζ (PKC‐ λ / ζ ) have been shown to be necessary for insulin‐, AICAR‐, and metformin‐stimulated glucose uptake in skeletal muscle, but not for treadmill exercise‐stimulated muscle glucose uptake. To investigate if PKC‐ λ / ζ activity is required for contraction‐stimulated muscle glucose uptake, we used mice with tibialis anterior muscle‐specific overexpression of an empty vector (WT), wild‐type PKC‐ ζ (PKC‐ ζ WT), or an enzymatically inactive T410A‐PKC‐ ζ mutant (PKC‐ ζ T410A). We also studied skeletal muscle‐specific PKC‐ λ knockout (M λ KO) mice. Basal glucose uptake was similar between WT, PKC‐ ζ WT, and PKC‐ ζ T410A tibialis anterior muscles. In contrast, in situ contraction‐stimulated glucose uptake was increased in PKC‐ ζ T410A tibialis anterior muscles compared to WT or PKC‐ ζ WT tibialis anterior muscles. Furthermore, in vitro contraction‐stimulated glucose uptake was greater in soleus muscles of M λ KO mice than WT controls. Thus, loss of PKC‐ λ / ζ activity increases contraction‐stimulated muscle glucose uptake. These data clearly demonstrate that PKC‐ λ  ζ activity is not necessary for contraction‐stimulated glucose uptake.