| Project/Area Number |
17390269
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | Kyoto University |
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Principal Investigator |
AKAMIZU Takashi Kyoto Univ., Dept. of Med., Associate Prof., 医学研究科, 助教授 (20231813)
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| Co-Investigator(Kenkyū-buntansha) |
IWAKURA Hiroshi Kyoto Univ., Dept. of Med., Assistant Prof., 医学研究科, 助手 (20378615)
ARIYASU Hiroyuki Kyoto Univ., Dept. of Med., Assistant Prof., 医学研究科, 助手 (50378650)
IRAKO Taiga Kyoto Univ., Dept. of Med., Research Fellow, 医学研究科, 研究員 (40402870)
KANGAWA Kenji National Cardiovascular Center Research Institute, Department of Biochemistry, Deputy Director, 研究所, 副所長 (00112417)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥15,300,000 (Direct Cost: ¥15,300,000)
Fiscal Year 2006: ¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 2005: ¥8,300,000 (Direct Cost: ¥8,300,000)
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| Keywords | Ghrelin / Diabetes / Pancreatic beta cell / Insulin / 膵臓β細胞 |
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| Research Abstract |
Ghrelin, a stomach-derived hormone, functions in multiple biological processes, including glucose metabolism and cellular differentiation and proliferation. In this study, we examined 'if early treatment with ghrelin can regenerate β cells of the pancreas in an animal model of diabetes mellitus, the nO-STZ model in which neonatal rats are injected with streptozotocin (STZ) at birth. Following administration of ghrelin to nO-STZ rats from postnatal days 2 to 8, we examined β-cell mass, mRNA expression levels of insulin and pdx-1 (pancreatic duodenal homeobox 1), and pancreatic morphology on days 21 and 70. In addition, we investigated the effects of ghrelin on β-cell replication. By day 21, ghrelin treatment increased pancreatic expression of insulin and pdx-1 mRNA in nO-STZ rats. The number of replicating cells was also significantly increased in the ghrelin-treated nO-STZ model. At day 70, nO-STZ rats exhibited hyperglycemia, despite slight increases in plasma insulin levels. Ghrelin treatment resulted in the improvement of plasma glucose levels associated with normal plasma insulin levels. Pancreatic insulin mRNA and protein levels were significantly increased in ghrelin-treated nO-STZ model animals. These findings suggest that ghrelin promotes regeneration of β cells in STZ-treated newborn rats. Furthermore, we attempted to examine effects of ghrelin on other diabetes models including adult STZ-injected rats, SDT (Spontaneously Diabetic Torii) rat and NOD (Non-obese diabetic) mice. In addition, we investigated effects of desacyl ghrelin on nO-STZ rats and found that desacyl ghrelin tended to prevent the development of hyperglycemia in this model.
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