Increased protein kinase C theta in skeletal muscle of diabetic patients

In this study we have investigated whether protein kinase C (PKC) protein and activity are increased in skeletal muscle of human diabetic patients. The protein content of different PKC isoforms (beta, theta, epsilon, delta, mu, and zeta) in the particulate fraction was measured, using Western analysis, in human rectus abdominus skeletal muscle from obese (hyperinsulinemic. normoglycemic) and obese diabetic (hyperinsulinemic, hyperglycemic) subjects, PKC theta protein content was significantly higher in the particulate fraction of muscle from diabetic patients compared with the nondiabetic controls. PKC theta was immunoprecipitated and its activity was measured in muscle from diabetic and nondiabetic controls. There was a significant increase in PKC theta activity in muscle from diabetic patients compared with muscle from nondiabetic controls. Therefore, both PKC theta protein content and activity were significantly increased in the particulate fraction in muscle from diabetic patients, suggesting the involvement of this isoform in diabetes. Most of the PKC a protein was found in the cytosol. There was no change in cytosolic PKC theta protein content in muscle from diabetic patients compared with muscle from nondiabetic controls. Thus, the increase in particulate-associated PKC theta was likely due to translocation and activation rather than an increase in protein mass. Copyright (C) 2001 by W.B. Saunders Company.