Charité-University School of Medicine, Department of Endocrinology Diabetes and Nutrition, Center for Cardiovascular Research, Berlin, Germany; Howard Hughes Medical Institute and the Departments of Internal Medicine and Cellular & Molecular Physiology, Yale University School of Medicine, New Haven, CT.
Hepatology. 2014 Feb;59(2):713-23. doi: 10.1002/hep.26672.
Nonalcoholic 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 (DAG) content leading to activation of novel protein kinase Cϵ (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.
非酒精性脂肪性肝病 (NAFLD)、肝胰岛素抵抗和 2 型糖尿病均密切相关，且均呈流行趋势。NAFLD 和肝胰岛素抵抗之间是否存在因果关系存在争议。本综述将讨论最近在人类和 NAFLD 动物模型中的研究，这些研究表明肝二酰基甘油 (DAG)含量的增加导致新型蛋白激酶 Cε (PKCε)的激活，从而导致与 NAFLD 相关的肝胰岛素抵抗和 2 型糖尿病发病机制中的胰岛素信号转导降低。DAG-PKCε 假说可以解释与肥胖、脂肪营养不良和 2 型糖尿病相关的大多数 NAFLD 中观察到的肝胰岛素抵抗的发生。
