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Nonalcoholic fatty liver disease, hepatic insulin resistance, and type 2 Diabetes
Author(s) -
Birkenfeld Andreas L.,
Shulman Gerald I.
Publication year - 2014
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.26672
Subject(s) - insulin resistance , nonalcoholic fatty liver disease , type 2 diabetes , medicine , endocrinology , fatty liver , diabetes mellitus , insulin , diacylglycerol kinase , obesity , disease , biology , protein kinase c , signal transduction , biochemistry
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. (H epatology 2014;59:713‐723)