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Association of local 11β-hydroxysteroid dehydrogenase type 2 with insulin secretion in pancreatic β-cells

Research Project

Project/Area Number 16590874
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionGifu University

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)

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)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
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)
KeywordsDiabetes Mullitus / 11β-HSD type 2 / CA repeat polymorphism / pancreatic β-cells
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.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (24 results)

All 2005 2004

All Journal Article (24 results)

  • [Journal Article] 11β・ヒドロキシステロイド脱水素酵素タイプ1欠損症2005

    • Author(s)
      宗 友厚, 他.
    • Journal Title

      日本臨床 63・S3

      Pages: 296-301

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 遺伝性血圧異常症の分子内分泌学2005

    • Author(s)
      宗 友厚, 他.
    • Journal Title

      医学のあゆみ 213・5

      Pages: 423-427

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Correlation between left ventricular mass and urinary sodium excretion in specific genotypes of CYP11B2.2005

    • Author(s)
      Isaji M, et al.
    • Journal Title

      J. Hypertens. 23・6

      Pages: 1149-1157

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Gene expression profile in rat pancreatic islet and RINm5F cells.2005

    • Author(s)
      Wang H, et al.
    • Journal Title

      J. Mol. Endocrinol. 35・1

      Pages: 1-12

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Association of Lys173Arg polymorphism with CYP11B2 expression level in normal adrenal glands and aldosterone-producing adenomas.2005

    • Author(s)
      Tanahashi H, et al.
    • Journal Title

      J. Clin. Endocrinol. Metab. 90・11

      Pages: 6226-6231

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Paraneoplastic neurologic syndrome and autoimmune addison disease in a patient with thymoma.2005

    • Author(s)
      Morita H, et al.
    • Journal Title

      Am. J. Med. Sci. 329・1

      Pages: 48-51

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 先天性副腎過形成による高血圧2005

    • Author(s)
      村松 学, 他.
    • Journal Title

      血圧 12・7

      Pages: 739-743

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] ステロイド薬の種類2005

    • Author(s)
      宗 友厚, 他.
    • Journal Title

      総合臨床 54・7

      Pages: 1992-1996

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Paraneoplastic neurologic syndrome and autoimmune addison disease in a patient with thymoma.2005

    • Author(s)
      Morita H, Hirota T, Mune T, et al.
    • Journal Title

      Am J Med Sci. 329(1)

      Pages: 48-51

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Correlation between left ventricular mass and urinary sodium excretion in specific genotypes of CYP11B2.2005

    • Author(s)
      Isaji M, Mune T, Takada N, et al.
    • Journal Title

      J Hypertens. 23(6)

      Pages: 1149-1157

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Gene expression profile in rat pancreatic islet and RINm5F cells.2005

    • Author(s)
      Wang H, Horikawa Y, Jin L, et al.
    • Journal Title

      J Mol Endocrinol. 35(1)

      Pages: 1-12

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Association of LysI73Arg polymorphism with CYP11B2 expression level in normal adrenal glands and aldosterone-producing adenomas.2005

    • Author(s)
      Tanahashi H, Mune T, Takahashi Y, et al.
    • Journal Title

      J Clin Endocrinol Metab. 90(11)

      Pages: 6226-6231

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Correlation between left ventricular mass and urinary sodium excretion in specific genotypes of CYP11B2.2005

    • Author(s)
      Isaji M, et al.
    • Journal Title

      J.Hypertens. 23・6

      Pages: 1149-1157

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Gene expression profile in rat pancreatic islet and RINm5F cells.2005

    • Author(s)
      Wang H, et al.
    • Journal Title

      J.Mol.Endocrinol 35・1

      Pages: 1-12

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Association of Lys173Arg polymorphism with CYP11B2 expression level in normal adrenal glands and aldosterone-producing adenomas.2005

    • Author(s)
      Tanahashi H, et al.
    • Journal Title

      I.Clin.Endocrinol.Metab 90・11

      Pages: 6226-6231

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Paraneoplastic neurologic syndrome and autoimmune addison disease in a patient with thymoma.2005

    • Author(s)
      Morita H, et al.
    • Journal Title

      Am.J.Med.Sci 329・1

      Pages: 48-51

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Plasma cortisol and cortisone concentrations in normal subjects and patients with adrenocortical disorders.2004

    • Author(s)
      Morita H, et al.
    • Journal Title

      Metabolism 53・1

      Pages: 89-94

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Depressive state and paresthesia dramatically improved by intravenous MgSO4 in Gitelman's syndrome.2004

    • Author(s)
      Enya M, et al.
    • Journal Title

      Intern. Med. 43・5

      Pages: 410-414

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Apparent Mineralocorticoid Excess症候群の現況2004

    • Author(s)
      宗 友厚, 他.
    • Journal Title

      ホルモンと臨床 52・8

      Pages: 101-107

    • NAID

      10013547212

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Plasma cortisol and cortisone concentrations in normal subjects and patients with adrenocortical disorders.2004

    • Author(s)
      Morita H, Isomura Y, Mune T, et al.
    • Journal Title

      Metabolism 53

      Pages: 89-94

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Depressive state and paresthesia dramatically improved by intravenous MgSO4 in Gitelman's syndrome.2004

    • Author(s)
      Enya M, Kanoh Y, Mune T, et al.
    • Journal Title

      Intern Med. 43(5)

      Pages: 410-414

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Plasma cortisol and cortisone concentrations in normal subjects and patients with adrenocortical disorders.2004

    • Author(s)
      Morita H, et al.
    • Journal Title

      Metabolism 53

      Pages: 89-94

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Depressive state and paresthesia dramatically improved by intravenous MgSO_4 in Gitelman's syndrome.2004

    • Author(s)
      Enya M, et al.
    • Journal Title

      Intern.Med. 43

      Pages: 410-414

    • Related Report
      2004 Annual Research Report
  • [Journal Article] TNFalpha reduces the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) via the production of ceramide and activation of atypical PKC.2004

    • Author(s)
      Kajita K, et al.
    • Journal Title

      Diabetes Res.Clin.Pract. 66

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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