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Hepatology. 2014 Feb;59(2):713-23. doi: 10.1002/hep.26672.

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

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1
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.

Abstract

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.

PMID:
23929732
PMCID:
PMC3946772
DOI:
10.1002/hep.26672
[Indexed for MEDLINE]
Free PMC Article
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