Development of therapeutics for diabetes with dysregulation of sleep/wake rhythm and depressive disorders by timed regulation of hypothalamic orexin system

2015 Fiscal Year Final Research Report

• Project/Area Number: 24390056
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Environmental physiology (including Physical medicine and Nutritional physiology)
• Research Institution: University of Toyama
• Principal Investigator: SASAOKA TOSHIYASU 富山大学, 大学院医学薬学研究部(薬学), 教授 (00272906)
• Co-Investigator(Kenkyū-buntansha): TSUNEKI HIROSHI 富山大学, 大学院医学薬学研究部(薬学), 准教授 (20332661) ; WADA TSUTOMU 富山大学, 大学院医学薬学研究部(薬学), 講師 (00419334)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: オレキシン / 不眠 / うつ / ストレス / 日内リズム / インスリン抵抗性 / 糖代謝

Outline of Final Research Achievements

Orexin system is involved in the regulation of both emotion and central glucose metabolism. Intracerebroventricular injection of orexin at active wake phase improved glucose metabolism via amelioration of ER stress responses and hepatic glucose production in diabetic db/db mice. In addition, orexin prevented chronic stress-induced glucose intolerance and insulin resistance in mice. Moreover, chronic nicotine treatment at active wake phase that enhances orexin expression improved glucose intolerance via inhibition of hepatic glucose production in db/db mice. Thus, orexin system plays a crucial role to centrally prevent glucose intolerance and hepatic insulin resistance caused by obesity and depression. The timed activation of orexin system is a new therapeutic target for diabetes with dysregulation of sleep/wake rhythm and/or depressive disorders.

Free Research Field

糖尿病・内分泌