The advisability of undertaking statin treatment of diabitics-pharmacological mechanism-based speculation

• Project/Area Number: 16590203
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Hokkaido Pharmaceutical University School of Pharmacy
• Principal Investigator: SATOH Kumi Hokkaido Pharmaceutical University School of Pharmacy, Associate Professor, 薬学部, 助教授 (00235334)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥2,900,000 (Direct Cost: ¥2,900,000); Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000); Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: 3T3L1 / Atorvastatin / Rab4 / Glut4 / Rab4 / スタチン / ストレプトゾトシン誘発糖尿病ラット / Goto-Kakizakiラット / Akt

Research Abstract

I examined the effects of statins on insulin signal transduction. Differentiated 3T3L1 adipocytes were treated with pravastatin (a.atorvastatin, simvastatin and fluvastatin) for 24 hours. The cell lysates were subjected to immunoblotting with various primary antibodies. The degree of phosphorylation on Ser-473 of the downstream kinase Akt was measured as an index of PI3K activation by insulin because PI3K is involved in insulin-mediated recruitment of glucose transporter-4 (GLUT4) The effect of statins on glucose uptake ability was determined by insulin-stimulated 2-deoxyglucose (2-DG) uptake. Any statins has no influence on insulin-stimulated phosphorylation of the insulin receptor. Atrvastatin but not pravastatin reduced the phosphorylation of Akt, localization in cytoplasmic membrane of RhoA and Rab4 and translocation to the plasma membrane of GLUT4. Atorvastatin, simvastatin and fluvastatin but not pravastatin suppressed the 2-DG uptake stimulated by insulin. These data imply that lipophilic statins disrupt insulin signaling by inhibition of RhoA and Rab4 prenylation.

Research Products

• [Journal Article] HMG-CoA Reductase Inhibitors do not Improve Glucose Intolerance in Spontaneously Diabetic Goto-Kakizaki Rats. (2005)
  • Author(s): Satoh K, Keimatsu N, Kanda M, Kasai T, Takaguri A, Sun F, Ichihara K
  • Journal Title: Biol Pharm Bull 28(11) Pages: 2092-2095
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Tetracycline protects myocardium against ischemic injury (2005)
  • Author(s): Kagawa N, Senbonmatsu TA, Satoh K, Ichihara K, Yamagata N, Hatano O, Saito T, Nguyen VQ, Waterman MR, Price E Jr, Atkinson JB, Inagami T
  • Journal Title: Front Biosci 10 Pages: 608-619
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] HMG-CoA Reductase Inhibitors do not Improve Glucose Intolerance in Spontaneously Diabetic Goto-Kakizaki Rats. (2005)
  • Author(s): Satoh K, Keimatsu N, Kanda M, Kasai T, Takaguri A, Sun F, Ichihara K
  • Journal Title: Biol Pharm Bull 28 Pages: 2092-2095
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Tetracycline protects myocardium against ischemic injury. (2005)
  • Author(s): Kagawa N, Senbonmatsu T, Satoh K et al.
  • Journal Title: Front Biosci. Vol.10 Pages: 608-19