| Project/Area Number |
13204074
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | WAKAYAMA MEDICAL UNIVERSITY |
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Principal Investigator |
NANJO Kishio WAKAYAMA MEDICAL UNIVERSITY, MEDICINE, PROFESSOR, 医学部, 教授 (40164511)
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| Co-Investigator(Kenkyū-buntansha) |
MORIKAWA Yoshihiro WAKAYAMA MEDICAL UNIVERSITY, MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (60230108)
NISHI Masahiro WAKAYAMA MEDICAL UNIVERSITY, MEDICINE, LECTURER, 医学部, 講師 (90228148)
FURUTA Hiroto WAKAYAMA MEDICALU NIVERSITY, MEDICINE, LECTURER, 医学部, 講師 (90238684)
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| Project Period (FY) |
2001 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥33,000,000 (Direct Cost: ¥33,000,000)
Fiscal Year 2004: ¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 2003: ¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 2002: ¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 2001: ¥10,000,000 (Direct Cost: ¥10,000,000)
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| Keywords | Leptin / Diabetes / SOD / UCP-2 / GPx-1 / BDNF / Ghrelin / Betacellulin / 肥満 / 遺伝要因 / 食欲調節 / 転写因子 |
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| Research Abstract |
To investigate the genetic factors involved in obese type 2 diabetes, we have identified leptin induced genes by PCR-select cDNA subtraction. One of genes identified was a novel transcriptional factor which polymorphism was related with obesity and overexpression this transcriptional factor in pancreatic beta cell line inhibited insulin gene promoter fumction. The analysis of UCP-2 promoter polymorphism revealed that it was related with insulin secretary function. We have identified the involvement of BDNF in leptin signaling. IA-2beta was identified as one of the ghrelin induced genes, and we have clarified its new role on the ghrelin's inhibitory effects on insulin secretion. Oxidative stress is very important for the pathogenesis of obesity and diabetes. Polymorphisms in antioxidant enzymes such as GPx-1 or SOD was investigated and correlation of GPx-1 polymorphism with macrovascular disease and intima-media thickness of carotid artery was identified. On the other hand, polymorphisms in SOD correlated with insulin resistance and onset age of diabetes. Betacellulin, a EGF family growth factor, is thought to be involved in pancreatic beta cell growth, neogenesis or apoptosis. Apolymorphism in promoterregion of betacellulin is associated with diabetes.
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