2015 Fiscal Year Final Research Report
To unveil mechanisms triggering pancreatic beta cell dysfunction in type 2 diabetes possibly via RAGE, glucolipotoxicity and insufficient leptin signaling.
| Project/Area Number |
25461335
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Yasuhiko 金沢大学, 医薬保健研究域医学系, 教授 (20313637)
Munesue Seiichi 金沢大学, 医薬保健研究域医学系, 助教 (10399040)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | 2型糖尿病 / 膵β細胞 / インスリン / RAGE / 糖脂肪毒性 |
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| Outline of Final Research Achievements |
Glucolipotoxicity, which is exerted by free fatty acids (FFA) and prolonged hyperglycemia, is implicated in pancreatic β-cell failure in diabetes. We examined whether advanced glycation end-products (AGE) and RAGE contribute to β-cell failure in a type 2 diabetes mouse model. Pretreatment of FFA combined with a leptin antagonist induced RAGE expression, AGE-elicited apoptosis, and impaired glucose-stimulated insulin secretion by AGE in MIN6 cells. FFA elevation with concomitant AGE formation during prolonged hyperglycemia could cause β-cell damage through insufficient leptin action and subsequent RAGE induction in type 2 diabetes.
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| Free Research Field |
糖尿病学、生化学
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