title: The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes.
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.
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Perry
authors.affiliation: 1] Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA. [2] VA Connecticut Healthcare System West Haven, Connecticut 06516, USA.
authors.forename: Varman T
authors.initials: VT
authors.lastname: Samuel
authors.affiliation: 1] Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA. [2] Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen DK-2200, Denmark.
authors.forename: Kitt F
authors.initials: KF
authors.lastname: Petersen
authors.affiliation: 1] Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA. [2] Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen DK-2200, Denmark. [3] Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. [4] Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06535-8012, USA.
authors.forename: Gerald I
authors.initials: GI
authors.lastname: Shulman
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D004075:Diglycerides / Q000378:metabolism; D005234:Fatty Liver / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008055:Lipids / Q000096:biosynthesis; D008060:Lipodystrophy / Q000378:metabolism; D050155:Lipogenesis; D008099:Liver / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease; D014280:Triglycerides / Q000096:biosynthesis
chemical_list: C011439:1,2-diacylglycerol; D004075:Diglycerides; D008055:Lipids; D014280:Triglycerides