Exercise Protects against Diet-Induced Insulin Resistance through Downregulation of Protein Kinase C[beta] in Mice

Physical exercise is an important and effective therapy for diabetes. However, its underlying mechanism is not fully understood. Protein kinase C[beta] (PKC[beta]) has been suggested to be involved in the pathogenesis of obesity and insulin resistance, but the role of PKC[beta] in exercise-induced improvements in insulin resistance is completely unknown. In this study, we evaluated the involvement of PKC[beta] in exercise-attenuated insulin resistance in high-fat diet (HFD)-fed mice. PKC[beta].sup.-/- and wild-type mice were fed a HFD with or without exercise training. PKC protein expression, body and tissue weight change, glucose and insulin tolerance, metabolic rate, mitochondria size and number, adipose inflammation, and AKT activation were determined to evaluate insulin sensitivity and metabolic changes after intervention. PKC[beta] expression decreased in both skeletal muscle and liver tissue after exercise. Exercise and PKC[beta] deficiency can alleviate HFD-induced insulin resistance, as evidenced by improved insulin tolerance. In addition, fat accumulation and mitochondrial dysfunction induced by HFD were also ameliorated by both exercise and PKC[beta] deficiency. On the other hand, exercise had little effect on PKC[beta].sup.-/- mice. Further, our data indicated improved activation of AKT, the downstream signal molecule of insulin, in skeletal muscle and liver of exercised mice, whereas PKC[beta] deficiency blunted the difference between sedentary and exercised mice. These results suggest that downregulation of PKC[beta] contributes to exercise-induced improvement of insulin resistance in HFD-fed mice.