| Project/Area Number |
01570625
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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 | Second Department of Internal Medicine, Chiba University School of Medicine |
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Principal Investigator |
KANATSUKA Azuma Chiba Uni. School of Med., 2 Dept. Internal Med. Assistant, 医学部, 助手 (40134366)
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| Co-Investigator(Kenkyū-buntansha) |
HASHIMOTO Naotake Chiba Uni. School of Med. 2 Dept Internal Med., Resident, 医学部, 医員
MAKINO Hideichi Chiba Uni. School of Med. 2 Dept. Internal Med., Lecturer, 医学部, 講師 (50009578)
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| Project Period (FY) |
1989 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1990: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1989: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Insular amyloid / Islet amyloid polypeptide / Amylin / Type 2 diabetes Mellitus / Gene / Pancreatic islets / Radioimmunoassay / Immunohistochemistry / 膵島アミロイド蛋白質 / islet amyloid polypeptide / インスリン非依存型糖尿病 / radioimmunoassay法 / ヒトIAPPcDNA / 膵B細胞 |
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| Research Abstract |
In type 2 diabetes mellitus, etiology remains to be elucidated, but amyloid is deposited within pancreatic islets and insular amyloid has been thought to be related to onset or progression of this disease. In 1987, islet amyloid polypeptide (IAPP), a main component of insular amyloid, was identified. We proposed to study this peptide and its gene, resolving the etiology of type 2 diabetes mellitus and developing the diagnostic method for this disease. In the first year, we planned to analyze IAPP gene and to develop an immunohistochemical method and a radioimmunoassay method for this peptide. Specific antibodies for IAPP was produced by immunization of oligopeptide to rabbits. These methods were developed by using the antibodies and specific for IAPP, thus, useful for studies of insular amyloid and IAPP. Because sequence of IAPP gene had been reported during preparation of this study, we stopped to investegate it. In the second year, we proposed to analyze IAPP gene in type 2 diabetic patients and to investigate relationship between this disease and IAPP. IAPP gene has been analyzed by means of a direct sequencing method. Using immunohistochemical method, insular amyloid was observed to be in 75.6% of 37 diabetic patients. IAPP is present in pancreatic B-cells and cosecreted with insulin in response to glucose. IAPP content in pancreas and secretion were increased in obese and diabetic experimental animals, suggesting that synthesis and secretion are aberrant in diabetic patients. Method for measurement of IAPP in blood was developed, and plasma IAPP levels have been measured in subjects with impaired glucose tolerance and diabetes mellitus.
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