期刊
DIABETES
卷 61, 期 5, 页码 1051-1061出版社
AMER DIABETES ASSOC
DOI: 10.2337/db11-1180
关键词
-
资金
- National Natural Science Foundation of China [81100866, 81130061]
- National Basic Research Program of China [2009CB521902]
- Program of Shanghai Subject Chief Scientist [10XD1405300]
- Shanghai 'Shu Guang' Project [10GG19]
- Second Military Medical University Young Investigator Foundation [2010QN06]
Whether the well-known metabolic switch AMP-activated protein kinase (AMPK) is involved in the insulin-sensitizing effect of calorie restriction (CR) is unclear. In this study, we investigated the role of AMPK in the insulin-sensitizing effect of CR in skeletal muscle. Wild-type (WT) and AMPK-alpha 2(-/-) mice received ad libitum (AL) or CR (8 weeks at 60% of AL) feeding. CR increased the protein level of AMPK-alpha 2 and phosphorylation of AMPK-a2. In WT and AMPK-alpha 2(-/-) mice, CR induced comparable changes of body weight, fat pad weight, serum triglycerides, serum nonesterified fatty acids, and serum leptin levels. However, decreasing levels of fasting/fed insulin and fed glucose were observed in WT mice but not in AMPK-alpha 2(-/-) mice. Moreover, CR-induced improvements of whole-body insulin sensitivity (evidenced by glucose tolerance test/insulin tolerance test assays) and glucose uptake in skeletal muscle tissues were abolished in AMPK-alpha 2(-/-) mice. Furthermore, CR-induced activation of Akt-TBC1D1/TBC1D4 signaling, inhibition of mammalian target of rapamycin - S6K1 - insulin receptor substrate-1 pathway, and induction of nicotinamide phosphoribosyltransferase - NAD(+)-sirtuin-1 cascade were remarkably impaired in AMPK-alpha 2(-/-) mice. CR serum increased stability of AMPK-alpha 2 protein via inhibiting the X chromosome-linked ubiquitin-specific protease 9-mediated ubiquitylation of AMPK-alpha 2. Our results suggest that AMPK may be modulated by CR in a ubiquitylation-dependent manner and acts as a chief dictator for the insulin-sensitizing effects of CR in skeletal muscle. Diabetes 61:1051-1061, 2012
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据