Nonalcoholic fatty liver disease, hepatic insulin resistance, and type 2 diabetes.

Nonalcoholic fatty liver disease, hepatic insulin resistance, and type 2 diabetes.
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DOI:
10.1002/hep.26672
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发表时间:
2014-02
期刊:
影响因子:
13.5
通讯作者:
Shulman, Gerald I.
Shulman, Gerald I.
中科院分区:
医学1区
文献类型:
--
作者:
Birkenfeld, Andreas L.;Shulman, Gerald I.

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非酒精性脂肪性肝病(NAFLD)、肝脏胰岛素抵抗和2型糖尿病都有很强的相关性,并且都达到了流行病的程度。NAFLD与肝脏胰岛素抵抗之间是否存在因果关系尚存争议。本文将讨论最近在NAFLD人类和动物模型中的研究,这些研究表明肝脏二酰基甘油含量的增加导致PKCε的激活,从而导致NAFLD相关肝脏胰岛素抵抗和2型糖尿病的胰岛素信号传导降低。DAG-PKCε假说可以解释大多数NAFLD与肥胖、脂肪营养不良和2型糖尿病相关的肝脏胰岛素抵抗的发生。
Non alcoholic fatty liver disease (NAFLD), hepatic insulin resistance and type 2 diabetes are all strongly associated and are all reaching epidemic proportions. Whether there is a causal link between NAFLD and hepatic insulin resistance is controversial. This review will discuss recent studies in both humans and animal models of NAFLD that have implicated increases in hepatic diacylglycerol content leading to activation of PKCε resulting in decreased insulin signaling in the pathogenesis of NAFLD associated hepatic insulin resistance and type 2 diabetes. The DAG-PKCε hypothesis can explain the occurrence of hepatic insulin resistance observed in most cases of NAFLD associated with obesity, lipodystrophy and type 2 diabetes.
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