| Project/Area Number |
14370341
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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 |
Metabolomics
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| Research Institution | JUNTENDO UNIVERSITY |
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Principal Investigator |
KAWAMORI Ryuzo Juntendo University, School of Medicine, Professor, 医学部, 教授 (00116021)
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| Co-Investigator(Kenkyū-buntansha) |
WATADA Hirotaka Juntendo University, School of Medicine, Lecturer, 医学部, 講師 (60343480)
TANAKA Yasuhi Juntendo University, School of Medicine, Associate Professor, 医学部, 助教授 (40276499)
INOUE Masahiro Osaka Medal Center In Cancer and Cardiovascular Disease, Chief director, 部長 (10342990)
HASHIZUME Hiroya Niigata University, School of Medicine, Lecturer, 大学院・医歯学総合研究科, 講師 (90261289)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥11,700,000 (Direct Cost: ¥11,700,000)
Fiscal Year 2004: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2003: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥5,400,000 (Direct Cost: ¥5,400,000)
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| Keywords | Pancreatic β cell / Pancreatic microcirculation / Diabetes Mellitus / VEGF-A / Cre recombinase / Insulin / 血管内皮 / インスリン分泌 / 膵微少循環 / Cre recombinas |
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| Research Abstract |
Altered regulation of insulin secretion and islet mass is characteristic of individuals with type 2 diabetes. While many previous studies reported the importance of several factors in b cells, there have been no clear studies showing the importance of islet vasculature in b cell function. In the present study, using the mice with disrupted VEGF-A gene specifically in b cells (RIP-Cre : Vegf^<fl/fl>) as model of impaired islet vasculature, we elucidated the relation between b cell function and islet vasculature. Electromicroscopic and immunohistochemical analysis identified reduced vascularization with the impaired formation of fenestrae and the increase in caveolae in endothelial cells in RIP-Cre : Vegf^<fl/fl> islets. While fasting glucose and body weight of RIP-Cre : Vegf^<fl/fl> mice were similar to control RIP-Cre and Vegf^<fl/fl> mice, RIP-Cre : Vegf^<fl/fl> mice exhibited impaired glucose tolerance with the decrease in rapid insulin release. However, glucose responsive insulin release assessed by batch incubation and perifusion studies using isolated islets from RLP-Cre : Vegf^<fl/fl> mice were not impaired. High fat diet for 12 weeks markedly deteriorated glucose tolerance and fasting glucose level in RIP-Cre : Vegf^<fl/fl> mice compared with control mice. However, high-fat-fed RIP-Cre : Vegf^<fl/fl> mice showed significant increase in islet mass compared with high-fat-fed control mice. Isolated islets from high-fat-fed RIP-Cre : Vegf^<fl/fl> mice exhibited enhanced glucose responsive insulin secretion. In summary, impaired rapid insulin release into blood stream observed in RIP-Cre : Vegf^<fl/fl> mice is due to abnormal quality and quantity of blood vessels in the islet, not due to the defect in β cells. With the existence of insulin resistance caused by high fat diet, these mice develop to diabetes without the failure of the regulation of islet mass.
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