Association of local 11β-hydroxysteroid dehydrogenase type 2 with insulin secretion in pancreatic β-cells
| Project/Area Number |
16590874
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Gifu University |
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Principal Investigator |
MUNE Tomoatu Gifu University, Graduate School of Medicine, Associate professor, 大学院・医学系研究科, 助教授 (70242732)
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| Co-Investigator(Kenkyū-buntansha) |
SASAKI Akihiko Gifu University, University Hospital, Research Associate, 医学部附属病院, 助手 (40334924)
SUWA Tetsuya Gifu University, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (30362164)
TAKEDA Jun Gifu University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (40270855)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Diabetes Mullitus / 11β-HSD type 2 / CA repeat polymorphism / pancreatic β-cells |
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| Research Abstract |
Type 2 11β-hydroxysteroid dehydrogenase encoded by the HSD11B2 gene converts cortisol to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. Here we analyzed the association of a highly polymorphic CA-repeat polymorphism in the first intron of HSD11B2 with glucose homeostasis. Distributions of short allele carried by each subject were bimodal and differed among groups, while no difference was observed in distributions of long allele. The frequencies of short allele length less than 19 CA repeats (median) was 33.9% in 388 normal subjects, 36.8% in 140 subjects with impaired glucose tolerance, and 23.3% in 212 patients with type 2 diabetes (x^2=5.13 vs. normal, P=0.021). In normal subjects without medication, urinary cortisol excretion was higher in subjects having longer length in the short allele, consistent with lower HSD11B2 expression in longer CA-repeat as previously reported. Furthermore, length of the long allele carried by each subject showed negative correlations with fasting plasma insulin level and a parameter of insulin resistance. Our results suggest that subjects having longer length in the short allele are susceptible for developing type 2 diabetes mellitus, probably via diminished insulin secretion by glucocorticoids.
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Report
(3 results)
Research Products
(24 results)
