| Project/Area Number |
13671183
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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 |
Metabolomics
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| Research Institution | OITA MEDICAL UNIVERSITY (2002)
Nagoya University (2001) |
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Principal Investigator |
NIKI Ichiro OITA MEDICAL UNIVERSITY, PROFESSOR, 医学部, 教授 (10262908)
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| Co-Investigator(Kenkyū-buntansha) |
SENDA Takao FUJITA HEALTH UNIVERSITY, SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (10187875)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | type 2 diabetes mellitus / calmodulin / transgenic mouse / apoptosis / insulin / pancreatic beta cell / sulphonylureas / NO (nitric oxide) |
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| Research Abstract |
We investigated the mechanisms of the pancreatic beta cell death at the onset of diabetes mellitus using transgenic mice overexpressing calmodulin in a beta cell specific manner. We found the transgenic mice experienced the beta cell death in as early stage of the onset, which was worsened by the anti-diabetic sulphonylurea tolbutamide. This means that Ca^<2+> influx by tolbutamide via closure of the ATP-sensitive K^+-channel may cause the beta cell death. Ca^<2+>, the central second messenger for insulin secretion, may possess a toxic effect on the beta-cell life as an inducer of apoptosis. We also found L-NAME, an inhibitor of nitric oxide synthase (NOS), retarded the onset of hyperglycemia in the transgenic mice. Isoform-specific immunostaining of pancreata demonstrated neural NOS might participate in the beta cell apoptosis. Prevention of hyperglycemia in the mouse model occurred partially, suggesting other mechanisms are involved. Because glucose-induced this transgenic mouse is a model to investigate beta cell exhaustion under diabetic conditions.
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