期刊
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
卷 292, 期 3, 页码 E677-E686出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00360.2006
关键词
carnitine palmitoyltransferase I; diacylglycerol; ceramides; triacylglycerides; protein kinase C
Oversupply of lipids to skeletal muscle causes insulin resistance by promoting the accumulation of lipid-derived metabolites that inhibit insulin signaling. In this study, we tested the hypothesis that overexpression of carnitine palmitoyltransferase I ( CPT I) could protect myotubes from fatty acid- induced insulin resistance by reducing lipid accumulation in the muscle cell. Incubation of L6E9 myotubes with palmitate caused accumulation of triglycerides, diacylgycerol, and ceramide, produced an activation of PKC theta and PKC zeta, and blocked insulin-stimulated glucose metabolism, reducing insulin- stimulated PKB activity by 60%. Transduction of L6E9 myotubes with adenoviruses encoding for liver CPT I ( LCPT I) wild- type ( WT), or a mutant form of LCPT I ( LCPT I M593S), which is insensitive to malonyl- CoA, produced a twofold increase in palmitate oxidation when LCPT I activity was increased threefold. LCPT I WT and LCPT I M593S- overexpressing L6E9 myotubes showed normal insulin- stimulated glucose metabolism and an improvement in PKB activity when pretreated with palmitate. Moreover, LCPT I WTand LCPT I M593S- transduced L6E9 myotubes were protected against the palmitate- induced accumulation of diacylglycerol and ceramide and PKC theta and - zeta activation. These results suggest that LCPT I overexpression protects L6E9 myotubes from fatty acid- induced insulin resistance by inhibiting both the accumulation of lipid metabolites and the activation of PKC theta and PKC zeta.
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