Intermolecular network involved in calcium-dependent apoptosis of pancreatic beta-cells and possible targets for diabetes treatment
| Project/Area Number |
20590085
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | University of Shizuoka |
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Principal Investigator |
ISHIKAWA Tomohisa University of Shizuoka, 薬学部, 教授 (10201914)
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| Co-Investigator(Kenkyū-buntansha) |
KANEKO Yukiko 静岡県立大学, 薬学部, 助教 (00381038)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 膵β細胞 / アポトーシス / カルシウム / ミトコンドリア / 酸化ストレス / 薬理学 / シグナル伝達 / 過酸化水素 / ストア作動性カルシウム流入 / IP_3受容体 / アネキシンV |
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| Research Abstract |
We investigated mechanisms for apoptosis induction in pancreatic beta-cells, which can be responsible for impairment of insulin secretion in type 2 diabetes. The treatment of beta-cell line INS-1 with H_2O_2, which resembled diabetic oxidative stress, induced a transient intracellular Ca^<2+> elevation. The response was mediated by Ca^<2+> release from the endoplasmic reticulum through IP3 receptors and terminated within one hour. This seemed to become a trigger signal for beta-cell apoptosis induction ; the transient cytosolic Ca^<2+> elevation led to prolonged elevation of mitochondrial Ca^<2+> concentration, thereby inducing cytochrome c release from mitochondria and beta-cell apoptosis.
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Report
(4 results)
Research Products
(55 results)
