Protein kinase C isozymes in skeletal muscles during the early stage of genetic and streptozocin diabetes.

This study examined the changes in PKC isozyme activity, content, and cellular distribution in rat gastrocnemius and soleus muscles prior to any evidence of neural degeneration or impaired skeletal muscle function, during the onset of streptozocin-induced (STZ) and genetic diabetes mellitus (DM). PKC activity was increased more in the particulate than in the soluble fractions of the soleus and gastrocnemius muscles obtained from rats treated with STZ and the gastrocnemius muscle obtained from BB-Wor diabetic rats (D rats). The predominant constitutive PKC isozymes in the skeletal muscles obtained from the STZ-treated and D rats were PKCalpha >> PKCepsilon > PKCdelta as determined by Western immunoblot assay. The content of each PKC isozyme did not differ between the soleus and gastrocnemius muscles of the control Sprague-Dawley rats for the STZ-treated rats and the BB Wor diabetic resistant (DR) rats. Moreover, the PKC isozyme content did not differ in the soluble fraction of D or STZ rats when compared to their corresponding control animals. PKCdelta increased more than PKCalpha or PKCepsilon in the particulate fraction of gastrocnemius and soleus muscles when obtained from either D or STZ rats. Since similar changes in skeletal muscle PKC isozyme profiles occurred independent of the duration of the diabetes and thereby the degree of nerve degeneration, insulin resistance, and the model of DM tested, we conclude that changes in skeletal muscle PKC precede the skeletal muscle myopathy of DM.