دورية أكاديمية
Loss of AMP-activated protein kinase-α2 impairs the insulin-sensitizing effect of calorie restriction in skeletal muscle.
| العنوان: | Loss of AMP-activated protein kinase-α2 impairs the insulin-sensitizing effect of calorie restriction in skeletal muscle. |
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| المؤلفون: | Wang P, Zhang RY, Song J, Guan YF, Xu TY, Du H, Viollet B, Miao CY, Wang, Pei, Zhang, Ruo-Yu, Song, Jie, Guan, Yun-Feng, Xu, Tian-Ying, Du, Hui, Viollet, Benoit, Miao, Chao-Yu |
| المصدر: | Diabetes; May2012, Vol. 61 Issue 5, p1051-1061, 11p |
| مستخلص: | 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-α2(-/-) mice received ad libitum (AL) or CR (8 weeks at 60% of AL) feeding. CR increased the protein level of AMPK-α2 and phosphorylation of AMPK-α2. In WT and AMPK-α2(-/-) 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-α2(-/-) 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-α2(-/-) 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-α2(-/-) mice. CR serum increased stability of AMPK-α2 protein via inhibiting the X chromosome-linked ubiquitin-specific protease 9-mediated ubiquitylation of AMPK-α2. 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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: | Complementary Index |
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