The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes

Rachel J. Perry, Varman T. Samuel, Kitt F. Petersen and Gerald I. Shulman ()
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Rachel J. Perry: Yale University School of Medicine
Varman T. Samuel: Yale University School of Medicine
Kitt F. Petersen: Yale University School of Medicine
Gerald I. Shulman: Yale University School of Medicine

Nature, 2014, vol. 510, issue 7503, 84-91

Abstract: Abstract Non-alcoholic fatty liver disease and its downstream sequelae, hepatic insulin resistance and type 2 diabetes, are rapidly growing epidemics, which lead to increased morbidity and mortality rates, and soaring health-care costs. Developing interventions requires a comprehensive understanding of the mechanisms by which excess hepatic lipid develops and causes hepatic insulin resistance and type 2 diabetes. Proposed mechanisms implicate various lipid species, inflammatory signalling and other cellular modifications. Studies in mice and humans have elucidated a key role for hepatic diacylglycerol activation of protein kinase Cε in triggering hepatic insulin resistance. Therapeutic approaches based on this mechanism could alleviate the related epidemics of non-alcoholic fatty liver disease and type 2 diabetes.

Date: 2014
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DOI: 10.1038/nature13478

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