Investigation the mechanism of hypoglycemic state induced atherogenic progression

Research Project

Project/Area Number	25750361
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Applied health science
Research Institution	Juntendo University
Principal Investigator	Goto Hiromasa 順天堂大学, 医学部, 助教 (90622746)
Project Period (FY)	2013-04-01 – 2016-03-31
Project Status	Completed (Fiscal Year 2015)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords	低血糖症 / 新生内膜形成 / アドレナリン作用 / 低血糖 / 動脈硬化 / 血管平滑筋 / カテコールアミン / プラーク破綻 / 動脈硬化症 / ｱﾄﾞﾚﾅﾘﾝ
Outline of Final Research Achievements	In this study,insulin was injected intraperitoneally into nonobese diabetic Goto-Kakizaki (GK) rats, once every3 days for 4 weeks after balloon injury of carotid artery to induce hypoglycemia. Then, we evaluated balloon injury-induced neointima formation. Insulin treatment enhanced neointima formation and increased the number of proliferating cell nuclear antigen (PCNA)-positive cells in the carotid artery. Injection of glucose with insulin prevented hypoglycemia and abrogated intimal thickening. Also, bunazosin, an α1 adrenergic receptor antagonist, prevented intimal thickening and accumulation of PCNA-positive cells induced by insulin treatment despite the presence of concomitant hypoglycemia and high adrenaline levels. Incubation of cultured smooth muscle cells with adrenaline resulted in a significant increase in their proliferation and G0/G1 to S phase progression These adrenaline-induced effects were abrogated by bunazosin.