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) iso-forms lambda and zeta (PKC-lambda/zeta) 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-lambda/zeta 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-zeta (PKC-zeta(WT)), or an enzymatically inactive T410A-PKC-zeta mutant (PKC-zeta(T410A)). We also studied skeletal muscle-specific PKC-lambda knockout (M lambda KO) mice. Basal glucose uptake was similar between WT, PKC-zeta(WT), and PKC-zeta(T410A) tibialis anterior muscles. In contrast, in situ contraction-stimulated glucose uptake was increased in PKC-zeta(T410A) tibialis anterior muscles compared to WT or PKC-zeta(WT) tibialis anterior muscles. Furthermore, in vitro contraction-stimulated glucose uptake was greater in soleus muscles of M lambda KO mice than WT controls. Thus, loss of PKC-lambda/zeta activity increases contraction-stimulated muscle glucose uptake. These data clearly demonstrate that PKC-lambda boxed dot zeta activity is not necessary for contraction-stimulated glucose uptake.