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 funct ion, during the onset of streptozocin-induced (STZ) and genetic diabet es mellitus (DM), PKC activity was increased more in the particulate t han in the soluble fractions of the soleus and gastrocnemius muscles o btained from rats treated with STZ and the gastrocnemius muscle obtain ed from BB-Wor diabetic rats (D rats). The predominant constitutive PK C isozymes in the skeletal muscles obtained from the STZ-treated and a rats were PKC alpha >> PKC epsilon > PKC delta as determined by Weste rn immunoblot assay. The content of each PKC isozyme did not differ be tween the soleus and gastrocnemius muscles of the control Sprague-Dawl ey rats for the STZ-treated rats and the BE Wor diabetic resistant (DR ) rats. Moreover, the PKC isozyme content did not differ in the solubl e fraction of a or STZ rats when compared to their corresponding contr ol animals. PKC delta increased more than PKC alpha or PKC epsilon in the particulate fraction of gastrocnemius and soleus muscles when obta ined from either a or STZ rats. Since similar changes in skeletal musc le PKC isozyme profiles occurred independent of the duration of the di abetes and thereby the degree of nerve degeneration, insulin resistanc e, and the model of DM tested, we conclude that changes in skeletal mu scle PKC precede the skeletal muscle myopathy of DM.