| Co-Investigator(Kenkyū-buntansha) |
SEINO Yutaka Kyoto University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (40030986)
KADAWAKI Takashi Graduate School of Medicine, University of Tokyo, Associate Professor, 大学院・医学系研究科, 助教授 (30185889)
OKA Yoshitomo Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (70175256)
NANJO Kishio Wakayama University of Medicine Science, Professor, 医学部, 教授 (40164511)
TAKEDA Jun Gunma University the Institute for Molecular and Cellular Regulation, Professor, 生体調節研究所, 教授 (40270855)
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| Budget Amount *help |
¥325,000,000 (Direct Cost: ¥325,000,000)
Fiscal Year 2002: ¥325,000,000 (Direct Cost: ¥325,000,000)
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| Research Abstract |
COLLABORATIVE STUDIES
DNA samples from 2,195 diabetic patients and 1,836 non-diabetic control subjects were collected and the clinical information was collected in a database. Association of amylin S20G with type 2 diabetes was found. A total of 33 SNPs of HNF-1α, HNF-1β, HNF-4α, Isl-1, PDX1, NGN3, PAX6, NKX2.2, NKX6.1, BETA2, SUR1, and Kir6.2 were genotyped and association study is now being performed.
Study group 1 (analysis of gene structure)
Association of SHP with mild obesity was found. Microarrays, each consisting of 20,000 ESTs from human or mouse islets, were developed. A major susceptibility gene Cblb was identified in an animal model of type 1 diabetes.
Study group 2 (analysis of gene function)
The contribution of the K_<ATP> channel to insulin secretion, type 2 diabetes and glucose homeostasis, the contribution of the NADH shuttle system to insulin secretion, the contribution of PPARγ to obesity and insulin resistance, the contribution of IRS-2 to diabetes, the contribution of adiponectin to insulin resistance, and the contribution of CREB/ATF family to diabetes were clarified. The novel cAMP sensor cAMP-GEFII was identified and its functional role in insulin secretion was determined.
Study group 3 (analysis of genes in disease states)
WFS1 was identified as the gene involved in Wolfram syndrome, and its subcellular localization was clarified. GIP signaling was found to be associated with both obesity and diabetes. The roles of PPARγ and PI3-K in insulin action also were clarified.
Study group 4 (genetic epidemiology)
Associations of HNF-4 α, HNF-1 β, Isl-1, Pax4, and syntaxin1A with type 2 diabetes were clarified. A novel method for the genetic analysis of complex diseases is being developed.
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