The mechanism of regulation on pancreatic beta cell mass by ER stress
| Project/Area Number |
22790861
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Metabolomics
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| Research Institution | Kobe University |
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Principal Investigator |
MATSUDA Tomokazu 神戸大学, 大学院・医学研究科, 医学研究員 (20570344)
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| Project Period (FY) |
2010 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | エネルギー・糖質代謝異常 / 小胞体ストレス / 膵β細胞量 / 糖尿病 |
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| Research Abstract |
The development of type 2 diabetes is accompanied by a progressive decline in.β-cell mass and function. Vildagliptin, a dipeptidyl peptidase-4 inhibitor, is representative of a new class of antidiabetic agents that act through increasing the expression of glucagon-like peptide-1. The protective effect of this agent on.β-cells was studied in diabetic mice. Diabetic pancreatic.β-cell-specific C/EBPB transgenic mice exhibit decreased.β-cell mass associated with increased apoptosis, decreased proliferation, and aggravated endoplasmic reticulum stress. Vildagliptin was orally administered to the transgenic mice for a period of 24 weeks, and the protective effects of this agent on.-cells were examined, along with the potential molecular mechanism of protection. Vildagliptin ameliorated hyperglycemia in transgenic mice by increasing the serum concentration of insulin and decreasing the serum concentration of glucagon. This agent also markedly increased.β-cell mass, improved aggravated endoplasmic reticulum stress, and restored attenuated insulin/insulin-like growth factor 1 signaling. A decrease in pancreatic and duodenal homeobox 1 expression was also observed in.β-cells isolated from our mouse model. Vildagliptin elicits protective effects on pancreatic.β-cells and has potential for preventing the progression of type 2 diabetes.
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Report
(3 results)
Research Products
(12 results)
