PKC-θ knockout mice are protected from fat-induced insulin resistance

来自 EBSCO

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阅读量：

167

作者：

JK Kim，JJ Fillmore，MJ Sunshine，B Albrecht，T Higashimori，DW Kim，ZX Liu，TJ Soos，GW Cline，WR O'Brien

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摘要：

Insulin resistance plays a primary role in the development of type 2 diabetes and may be related to alterations in fat metabolism. Recent studies have suggested that local accumulation of fat metabolites inside skeletal muscle may activate a serine kinase cascade involving protein kinase C-theta (PKC-theta), leading to defects in insulin signaling and glucose transport in skeletal muscle. To test this hypothesis, we examined whether mice with inactivation of PKC-theta are protected from fat-induced insulin resistance in skeletal muscle. Skeletal muscle and hepatic insulin action as assessed during hyperinsulinemic-euglycemic clamps did not differ between WT and PKC-theta KO mice following saline infusion. A 5-hour lipid infusion decreased insulin-stimulated skeletal muscle glucose uptake in the WT mice that was associated with 40-50% decreases in insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-1-associated PI3K activity. In contrast, PKC-theta inactivation prevented fat-induced defects in insulin signaling and glucose transport in skeletal muscle. In conclusion, our findings demonstrate that PKC-theta is a crucial component mediating fat-induced insulin resistance in skeletal muscle and suggest that PKC-theta is a potential therapeutic target for the treatment of type 2 diabetes.

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关键词：

Fat-Induced Insulin Resistances Knockout Mice Glucose Transport Insulin Resistance Fat Metabolisms

DOI：

10.1172/JCI22230

被引量：

2057

年份：

2004