College of Public Health, The Ohio State University, Columbus, Ohio, United States of America.
Davis Heart & Lung Research Institute, The Ohio State University, Columbus, Ohio, United States of America.
PLoS One. 2013 Dec 9;8(12):e81364. doi: 10.1371/journal.pone.0081364. eCollection 2013.
Physical exercise is an important and effective therapy for diabetes. However, its underlying mechanism is not fully understood. Protein kinase Cβ (PKCβ) has been suggested to be involved in the pathogenesis of obesity and insulin resistance, but the role of PKCβ in exercise-induced improvements in insulin resistance is completely unknown. In this study, we evaluated the involvement of PKCβ in exercise-attenuated insulin resistance in high-fat diet (HFD)-fed mice. PKCβ(-/-) 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. PKCβ expression decreased in both skeletal muscle and liver tissue after exercise. Exercise and PKCβ 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 PKCβ deficiency. On the other hand, exercise had little effect on PKCβ(-/-) mice. Further, our data indicated improved activation of AKT, the downstream signal molecule of insulin, in skeletal muscle and liver of exercised mice, whereas PKCβ deficiency blunted the difference between sedentary and exercised mice. These results suggest that downregulation of PKCβ contributes to exercise-induced improvement of insulin resistance in HFD-fed mice.
体育锻炼是糖尿病的一种重要且有效的治疗方法。然而，其潜在机制尚未完全阐明。蛋白激酶 Cβ（PKCβ）已被认为与肥胖和胰岛素抵抗的发病机制有关，但 PKCβ 在运动引起的胰岛素抵抗改善中的作用尚完全未知。在这项研究中，我们评估了 PKCβ 在高脂饮食（HFD）喂养的小鼠运动减轻胰岛素抵抗中的作用。将 PKCβ（-/-）和野生型小鼠用 HFD 喂养，或同时进行运动训练。测定 PKC 蛋白表达、体重和组织重量变化、葡萄糖和胰岛素耐量、代谢率、线粒体大小和数量、脂肪炎症以及 AKT 激活情况，以评估干预后胰岛素敏感性和代谢变化。运动后，骨骼肌和肝组织中的 PKCβ 表达均降低。运动和 PKCβ 缺失可减轻 HFD 诱导的胰岛素抵抗，表现为胰岛素耐量改善。此外，HFD 引起的脂肪堆积和线粒体功能障碍也通过运动和 PKCβ 缺失得到改善。另一方面，运动对 PKCβ（-/-）小鼠几乎没有影响。此外，我们的数据表明，运动可增强胰岛素下游信号分子 AKT 在骨骼肌和肝脏中的激活，而 PKCβ 缺失则削弱了安静和运动小鼠之间的差异。这些结果表明，PKCβ 的下调有助于 HFD 喂养的小鼠运动诱导的胰岛素抵抗改善。
