Development of therapeutics for diabetes with dysregulation of sleep/wake rhythm and depressive disorders by timed regulation of hypothalamic orexin system
| 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
|
| Project Status |
Completed (Fiscal Year 2015)
|
| Budget Amount *help |
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2014: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2013: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
|
|---|
| 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 / 肝糖新生 / ERストレス / 時計遺伝子 |
|---|
| 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.
|
Report
(5 results)
Research Products
(43 results)
-
[Journal Article] Nighttime administration of nicotine improves hepatic glucose metabolism via the hypothalamic orexin system in mice.2016
Author(s)
Tsuneki H, Nagata T, Fujita M, Kon K, Wu N, Takatsuki M, Yamaguchi K, Wada T, Nishijo H, Yanagisawa M, Sakurai T, Sasaoka T.
-
Journal Title
Endocrinology
Volume: 157
Issue: 1
Pages: 195-206
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
-
-
[Journal Article] Hypothalamic orexin prevents hepatic insulin resistance via daily bidirectional regulation of autonomic nervous system in mice.2015
Author(s)
Tsuneki H, Tokai E, Nakamura Y, Takahashi K, Fujita M, Asaoka T, Kon K, Anzawa Y, Wada T, Takasaki I, Kimura K, Inoue H, Yanagisawa M, Sakurai T, Sasaoka T.
-
Journal Title
Diabetes
Volume: 64
Issue: 2
Pages: 459-470
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
-
-
[Journal Article] Rational design and synthesis of 4-substituted 2-pyridin-2-ylamides with inhibitory effects on SH2 domain-containing inositol 5'-phosphatase 2 (SHIP2).2013
Author(s)
Ichihara Y, Fujimura R, Tsuneki H, Wada T, Okamoto K, Gouda H, Hirono S, Sugimoto K, Matsuya Y, Sasaoka T, Toyooka N.
-
Journal Title
Eur J Med Chem.
Volume: 62
Pages: 649-660
DOI
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
