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首页> 外文期刊>Cell metabolism >Hepatic Mitochondrial Pyruvate Carrier 1 Is Required for Efficient Regulation of Gluconeogenesis and Whole-Body Glucose Homeostasis
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Hepatic Mitochondrial Pyruvate Carrier 1 Is Required for Efficient Regulation of Gluconeogenesis and Whole-Body Glucose Homeostasis

机译：肝线粒体丙酮酸载体1是有效调节糖异生和全身葡萄糖体内平衡所必需的。

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摘要

Gluconeogenesis is critical for maintenance of euglycemia during fasting. Elevated gluconeogenesis during type 2 diabetes (T2D) contributes to chronic hyperglycemia. Pyruvate is a major gluconeogenic substrate and requires import into the mitochondrial matrix for channeling into gluconeogenesis. Here, we demonstrate that the mitochondrial pyruvate carrier (MPC) comprising the Mpc1 and Mpc2 proteins is required for efficient regulation of hepatic gluconeogenesis. Liver-specific deletion of Mpc1 abolished hepatic MPC activity and markedly decreased pyruvate-driven gluconeogenesis and TCA cycle flux. Loss of MPC activity induced adaptive utilization of glutamine and increased urea cycle activity. Diet-induced obesity increased hepatic MPC expression and activity. Constitutive Mpc1 deletion attenuated the development of hyperglycemia induced by a high-fat diet. Acute, virally mediated Mpc1 deletion after diet-induced obesity decreased hyperglycemia and improved glucose tolerance. We conclude that the MPC is required for efficient regulation of gluconeogenesis and that the MPC contributes to the elevated gluconeogenesis and hyperglycemia in T2D.
机译：糖原异生对于禁食期间维持正常血糖至关重要。 2型糖尿病（T2D）期间糖异生增高可导致慢性高血糖症。丙酮酸是主要的糖原异生底物，需要导入线粒体基质中才能引导糖原异生。在这里，我们证明了包含Mpc1和Mpc2蛋白的线粒体丙酮酸载体（MPC）是肝糖异生的有效调节所必需的。 Mpc1的肝特异性删除取消了肝MPC活性，并显着降低了丙酮酸驱动的糖异生和TCA循环通量。 MPC活性的丧失导致谷氨酰胺的适应性利用和尿素循环活性的增加。饮食引起的肥胖增加了肝MPC的表达和活性。组成性Mpc1缺失减弱了高脂饮食诱导的高血糖症的发生。饮食引起的肥胖后，由病毒介导的急性Mpc1缺失减少了高血糖症并改善了糖耐量。我们得出结论，MPC是糖原异生的有效调节所必需的，并且MPC有助于T2D中糖原异生和高血糖的升高。

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