title: Eicosapentaenoic acid ameliorates hyperglycemia in high-fat diet-sensitive diabetes mice in conjunction with restoration of hypoadiponectinemia.
abstract: OBJECTIVE
  Eicosapentaenoic acid (EPA) exerts pleiotropic effects on metabolic disorders such as atherosclerosis and dyslipidemia, but its effectiveness in the treatment of type 2 diabetes mellitus remains controversial.
  
  
  METHODS
  We examined the antidiabetic effect of EPA in insulin receptor mutant (Insr(P1195L/+)) mice that exhibit high-fat diet (HFD)-dependent hyperglycemia.
  
  
  RESULTS
  EPA supplementation was found to alleviate hyperglycemia of Insr(P1195L/+) mice fed HFD (Insr(P1195L/+)/HFD mice), which was accompanied by amelioration of increased gluconeogenesis and impaired insulin signaling, as assessed by glucose-6-phosphatase (G6pc) expression on refeeding and insulin-induced phosphorylation of Akt in the liver, respectively. We found that serum levels of adiponectin, the antidiabetic adipokine, were decreased by HFD along with the body weight gain in Insr(P1195L/+) mice but not in wild-type mice, suggesting that Insr(P1195L/+) mice are prone to hypoadiponectinemia in response to obesity. Interestingly, the blood glucose levels of Insr(P1195L/+) mice were in reverse proportion to their serum adiponectin levels and EPA supplementation ameliorated their hyperglycemia in conjunction with the restoration of hypoadiponectinemia.
  
  
  CONCLUSIONS
  EPA exerts an antidiabetic effect in Insr(P1195L/+)/HFD mice, an HFD-sensitive, insulin-resistant animal model, possibly through its action against hypoadiponectinemia.
authors.affiliation: Department of Medical Physiology, Chiba University, Graduate School of Medicine, Chiba, Japan.|Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Morimoto
authors.affiliation: Department of Medical Physiology, Chiba University, Graduate School of Medicine, Chiba, Japan.
authors.forename: E-Y
authors.initials: EY
authors.lastname: Lee
authors.affiliation: Department of Medical Physiology, Chiba University, Graduate School of Medicine, Chiba, Japan.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Metabolism and Nutrition Research Unit, Innovative Integrated Bio-Research Core, Institute for Frontier Science Initiative, Kanazawa University, Kanazawa, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Inaba
authors.affiliation: Metabolism and Nutrition Research Unit, Innovative Integrated Bio-Research Core, Institute for Frontier Science Initiative, Kanazawa University, Kanazawa, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Inoue
authors.affiliation: Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ogawa
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: T
authors.initials: T
authors.lastname: Shirasawa
authors.affiliation: Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Yokosuka
authors.affiliation: Department of Medical Physiology, Chiba University, Graduate School of Medicine, Chiba, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Miki
mesh_terms: D052242:Adiponectin / Q000172:deficiency* / Q000378:metabolism; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D059305:Diet, High-Fat; D019587:Dietary Supplements; D004195:Disease Models, Animal; D015118:Eicosapentaenoic Acid / Q000494:pharmacology* / Q000627:therapeutic use*; D006943:Hyperglycemia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008661:Metabolism, Inborn Errors / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects
chemical_list: D052242:Adiponectin; D015118:Eicosapentaenoic Acid