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研究発表を行う予定の学会；
・ADA scientific meeting
　２０１２年　６月　８日〜１２日（Philadelphia, USA）

タイトル；Combination of dipeptidylpeptidase-IV inhibitor, Vildagliptin and angiotensin-II receptor blocker, Varsaltan ameliorates both insulin insufficiency and insulin resistance in mouse models of type 2 diabetes.

発表者；宮川　克俊　氏
　　　（熊本大学　大学院生命科学研究部　代謝内科学分野）
Abstract；
DPP-4 inhibitors improve pancreatic β-cell function by suppression of GLP-1 degradation, and angiotensin-II receptor blockers reduce incidence of type 2 diabetes (T2DM). We hypothesize that the combination of these two drugs acts in a synergistic manner on islet function and insulin sensitivity.
To test this hypothesis, phlorizin (PHZ), Vildagliptin (ViL: 1 mg/kg/day) and/or Valsartan (VaL: 10 mg/kg/day) were administered to high-fat diet (HFD) induced diabetic or db/db mice for 8 weeks. Islet morphology, biochemical markers and insulin signaling were investigated.
BW and food intake were both unaltered by ViL and/or VaL treatment. Fasting and random fed blood glucose levels were significantly decreased in PHZ, ViL and ViL+VaL treatments in both HFD and db/db mice. Most effective suppression of random fed blood glucose was observed in ViL+VaL treated db/db mice. Upon i.p.GTT, ViL+VaL treatment group showed most profound suppression of glucose excursion in both mice. ViL+VaL treatment displayed significant increase of insulin secretion in db/db mice upon glucose challenge. In addition, ViL+VaL treatment showed improvement of insulin sensitivity in db/db mice.
CRP, TNF-α, IL-6 and MCP-1 were all significantly decreased, and adiponectin was highest in ViL+VaL group. ViL+VaL show improved insulin signaling and attenuated ER stress in liver. ViL+VaL treatment group increased insulin contents in db/db islets. Furthermore, immunohistochemical analysis of the pancreas revealed that the combination treatment resulted in an increased expression of insulin, PDX1, and maintenance of normal β/α-cell distribution.
In conclusion, the combination therapy of ViL and VaL improves both pancreatic β-cell function and insulin sensitivity in mice models of T2DM. This combination therapy may be useful in subjects with T2DM and hypertension.