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 (Mλ 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 Mλ 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.