1994 Fiscal Year Final Research Report Summary
Studies on human ialet amyloid polypeptide gene expression and non-insulin-dependent diabetes
| Project/Area Number |
05670838
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | Chiba University |
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Principal Investigator |
KANATSUKA Azuma Chiba Uni.School of Med.2nd Dept.of Internal Med., Lecturer., 医学部, 講師 (40134366)
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| Project Period (FY) |
1993 – 1994
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| Keywords | islet amyloid polypeptide / amylin / non-insulin-dependent diabetes mellitus / islet amyloid / insulin secretion / transformed pancreatic Beta-cells / transgenic mouse / transfection |
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| Research Abstract |
Islet amyloid the most significant pathological finding in human non-insulin-dependent diabetes mellitus (NIDDM) and islet amyloid polypeptide (IAPP) /amylin is a major component of the amyloid. We proposed to resolve the relationship between IAPP gene expression and onset or progression of NIDDM.
1. We had developed transgenic mouse expressing human IAPP.In the transgenic mice, amyloid-like fibrils were formed in secretory granules of pancreatic Beta-cells, suggesting that IAPP-derived amyloid fibrils are formed in secretory granules, released and aggregated into amyloid deposits in human NIDDM.Glucose tolerance was normal in the transgenic mice. After long-term feeding with sucrose or high fat diet, glucose tolerance remained to be normal, suggesting that onset of diabets mellitus is not induced only by human IAPP expression.
2. We tried to introduce human IAPP cDNA in transfomed mouse pancreatic Beta-cells by transfection method and succeeded in the development of pancreatic Beta-cell line expressing human IAPP.Although insulin synthesis was not influenced by human IAPP expression, glucose-induced insulin secretion was markedly depressed. From these results, we conclude that overexpression of IAPP might impaire insulin secretion in NIDDM.
The present studies are useful to understand a relationship among IAPP gene expression, islet amyloid deposition and onset or progression of NIDDM.
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[Publications] Kazuo Yagui, Takahide Yamaguchi, Azuma Kanatsuka, Fumio Shimada, Choug I Huang, Yoshiharu Tokuyama, Haruhiko Ohsawa, Ken-ichi Yamamura, Jun-ichi Miyazaki, Atsuo Mikata, Sho Yoshida, Hideichi Makino: "Formation of islet amyloid fibrils in beta-secretory granules of transgenic mice expressing human islet amyloid polypeptide/amylin." European Journal of Endocrinology. 12 (in press). (1995)
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