Exercise protects against diet-induced insulin resistance through downregulation of protein kinase Cβ in mice.
Exercise protects against diet-induced insulin resistance through downregulation of protein kinase Cβ in mice.
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DOI：
10.1371/journal.pone.0081364
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Sun Q
中科院分区：
文献类型：
--
作者：
Rao X;Zhong J;Xu X;Jordan B;Maurya S;Braunstein Z;Wang TY;Huang W;Aggarwal S;Periasamy M;Rajagopalan S;Mehta K;Sun Q
体育锻炼是治疗糖尿病的重要而有效的方法。然而，其基本机制尚未完全了解。蛋白激酶Cβ（PKCβ）被认为参与肥胖和胰岛素抵抗的发病机制，但PKCβ在运动诱导的胰岛素抵抗改善中的作用尚不清楚。在这项研究中，我们评估了PKCβ参与运动减弱高脂饮食（HFD）喂养小鼠的胰岛素抵抗。给PKCβ-/-和野生型小鼠喂食HFD，伴或不伴运动训练。通过测定PKC蛋白表达、体重和组织重量变化、葡萄糖和胰岛素耐受性、代谢率、线粒体大小和数量、脂肪炎症和AKT活化来评估干预后的胰岛素敏感性和代谢变化。运动后骨骼肌和肝组织中PKCβ表达均下降。运动和PKCβ缺乏可以减轻HFD诱导的胰岛素抵抗，如胰岛素耐受性改善所证明的。此外，运动和PKCβ缺乏也可改善HFD诱导的脂肪蓄积和线粒体功能障碍。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，运动小鼠骨骼肌和肝脏中胰岛素下游信号分子AKT的活化得到改善，而PKCβ缺乏减弱了久坐和运动小鼠之间的差异。这些结果表明，PKCβ的下调有助于运动诱导的HFD喂养小鼠胰岛素抵抗的改善。
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.
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影响因子：
5.8
作者：
Oberbach, Andreas;Lehmann, Stefanie;Kovacs, Peter
通讯作者：
Kovacs, Peter
影响因子：
15.9
作者：
Bonnard, Charlotte;Durand, Annie;Rieusset, Jennifer
通讯作者：
Rieusset, Jennifer
DOI：
10.1073/pnas.2536828100
发表时间：
2003-12-23
影响因子：
11.1
作者：
He, WM;Barak, Y;Evans, RM
通讯作者：
Evans, RM
影响因子：
20.1
作者：
Geraldes P;King GL
通讯作者：
King GL
影响因子：
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作者：
GOLDSTEIN, MS;MULLICK, V;LEVINE, R
通讯作者：
LEVINE, R