Clarification of the mechanism by which the impairment of intra-hepatic cellular network caused hepatic insulin resistance in mice.

• Project/Area Number: 20790641
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Metabolomics
• Research Institution: University of Toyama
• Principal Investigator: WADA Tsutomu University of Toyama, 医学薬学研究部, 助教 (00419334)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: メタボリックシンドローム / NAFLD / NASH / アルドステロン

Research Abstract

We examined the effect of spironolactone on glucose and lipid metabolism in a mouse model with diet-induced diabetes and non-alcoholic fatty liver disease (NAFLD). C57BL/6 mice were fed control diet, 60% fat diet with 30% fructose water (HFFD), or HFFD with spironolactone for 8 weeks. HFFD mice demonstrated apparent phenotypes of metabolic syndrome, including insulin resistance, hypertension, dyslipidemia, and fatty liver. Administration of spironolactone effectively ameliorated these phenotypes. These results indicate that inhibition of MR might be a beneficial therapeutic approach for diet-induced phenotypes of metabolic syndrome and fatty liver.

Research Products

• [Journal Article] Spironolactone improves glucose and lipid metabolism by ameliorating hepatic steatosis and inflammation, and suppressing enhanced gluconeogenesis induced by high-fat and high-fructose diet. (2010)
  • Author(s): Wada T, Kenmochi H, Miyashita Y, Sasaki M, Ojima M, Sasahara M, Koya D, Tsuneki H, Sasaoka T.
  • Journal Title: Endocrinology (in press)
• [Journal Article] Spironolactone Improves Glucose and Lipid Metabolism by Ameliorating Hepatic Steatosis and Inflammation and Suppressing Enhanced Gluconeogenesis Induced by High-Fat and High-Fructose Diet (2010)
  • Author(s): Wada T, Kenmochi H, MiyashitaY, Sasaki M, Ojima M, Sasahara M, Kova D, Tsuneki H, Sasaoka
  • Journal Title: Endocrinology 151 Pages: 2040-2049
  • Peer Reviewed
• [Journal Article] Aldosterone inhibits insulin -induced glucose uptake by degradation of insulin receptor substrate (IRS) 1 and IRS2 via a reactive oxygen species-mediated pathway in 3T3-L1 adipocytes. (2009)
  • Author(s): Wada T, Ohshima S, Fujisawa E, Koya D, Tsuneki H, Sasaoka T.
  • Journal Title: Endocrinology 150 Pages: 1662-9
• [Journal Article] Aldosterone Inhibits Insulin-Induced Glucose Uptake by Degradation of IRS1 and IRS2 via an ROS-Mediated Pathway in 3T3-L1 Adipocytes. (2009)
  • Author(s): Wada T, Ohshima S, Fujisawa E, Koya D, Tsuneki H, Sasaoka T
  • Journal Title: Endocrinology 150 Pages: 1662-1669
  • Peer Reviewed
• [Journal Article] Aldosterone Inhibits Insulin-Induced Glucose Uptake by Degradation of IRS1 and IRS2 via an ROS-Mediated Pathway in 3T3-L1 Adipocytes (2009)
  • Author(s): Wada T, Ohshima S, Fujisawa E, Koya D, Tsuneki H, Sasaoka T
  • Journal Title: Endocrinology 150(In press)
  • Peer Reviewed
• [Presentation] 高脂質高フルクトース負荷マウスのメタボリックシンドローム病態に対する抗アルドステロン薬の改善効果. (2010)
  • Author(s): 宮下佑介、和田努、剱持弘樹、佐々木元大、恒枝宏史、笹原正清、笹岡利安
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: 岡山
• [Presentation] Spironolactone improves glucose and lipid metabolism and ameliorates hepatic steatosis induced by high-fat and high-fructose diet. (2010)
  • Author(s): Wada T, Miyashita Y, Sasaki M, Kenmochi H, Sasahara M, Tsuneki H, Sasaoka T.
  • Organizer: American Diabetes Association's 70th Scientific Sessions
  • Place of Presentation: Orlando, FL, USA
• [Presentation] 高脂質高フルクトース負荷マスのメタボリックシンドローム病態に対する抗アルドステロン薬の改善効果 (2010)
  • Author(s): 呂下佑、和田努、剱持弘樹、佐々木元大、恒枝宏史、笹原正清、笹岡利安
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: 岡山
• [Presentation] Spironolactone improves glucose and lipid metabolism and ameliorates hepatic steatosis induced by high-fat and high-fructose diet (2010)
  • Author(s): Wada T, Miyashita Y, Sasaki M , Kenmochi H, Sasahara M, Tsuneki H, Sasaoka T
  • Organizer: American Diabetes Association's 70th Scientific Sessions
  • Place of Presentation: Orlando, FL, USA
• [Presentation] Spironolactone improves glucose and lipid metabolism by ameliorating hepatic steatosis, inflammation, and suppressing enhanced gluconeogenesis induced by high-fat and high-fructose diet. (2009)
  • Author(s): Wada T, Kenmochi H, Miyashita Y, Sasaki M, Sasahara M, Tsuneki H, Sasaoka T.
  • Organizer: 第2回Insulin Resistance in Metabolic Disease Forum
  • Place of Presentation: Tokyo
  • Year and Date: 2009-10-31
• [Presentation] Spironolactone improves glucose and lipid metabolism by amelior ating hepatic steatosis, inflammation, and suppressing enhanced gluconeogenesis induced by high-fat and high-fructose diet. (2009)
  • Author(s): Wada T, Kenmochi H, Miyas hita Y, Sasaki M, Sasahara M, Tsuneki H, Sasaoka T
  • Organizer: 第2回 Insulin Resistance in Metabolic Disease Forum
  • Place of Presentation: Tokyo
  • Year and Date: 2009-10-31
• [Presentation] Spironolactone ameliorates glucose and lipid metabolism by suppressing enhanced gluconeogenesis and hepatic inflammation with fatty liver in mice with diet-induced metabolic syndrome. (2009)
  • Author(s): Wada T. Kenmochi H. Miyashita Y. Sasaki M, Tsuneki H, Sasahara M, Sasaoka T.
  • Organizer: The 2nd International Aldosterone Forum in Japan
  • Place of Presentation: Tokyo
• [Presentation] Spironolactone ameliorates glucose and lipid metabolism by supp ressing enhanced gluconeogenesis and hepatic inflammation with fatty liver in mice with diet-induced metabolic syndrome. (2009)
  • Author(s): Wada T.Kenmochi H.Miyashita Y.Sasaki M, Tsuneki H, Sasahara M, Sasaoka T.
  • Organizer: The 2nd International Aldosterone Forum in Japan
  • Place of Presentation: Tokyo
• [Presentation] Novel Mechanisms of Aldosterone-Induced Inhibition on Insulin's Metabolic Signaling in 3T3-L1 Adipocytes (2008)
  • Author(s): Sasaoka T, Wada T
  • Organizer: Annual meeting of American diabetes association
  • Place of Presentation: サンフランシスコ、USA
  • Year and Date: 2008-06-03