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Signaling axis of urotensin II, parasympathetic nerves, and nitric oxide on carbohydrate metabolism: A clinical

Research Project

Project/Area Number 17590912
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

TAMURA Akira  Tohoku University, Hospital, Research Associate, 病院, 助手 (00375023)

Co-Investigator(Kenkyū-buntansha) HINOKIO Yoshinori  Tohoku University, Graduate School of Medicine, Associate Professor, 大学院医学系研究科, 助教授 (10282071)
SUZUKI Susumu  Tohoku University, Graduate School of Medicine, Lecturer, 大学院医学系研究科, 講師 (70216399)
ISHIHARA Hisamitsu  Tohoku University Hospital, Research Associate, 病院・講師 (60361086)
高橋 和眞  東北大学, 病院・助手 (60292215)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsDiabetes / Urotensin II / Parasympatic nerve / Nitric Oxide / Insulin / Liver / Gene knockdown
Research Abstract

We reported that genetic polymorphisms of urotensin II, UTS2, one of most potent vasoactive polypeptides, might be contributed to in vivo insulin sensitivity, resulting to the onset of diabetes.
To elucidate possible roles of urotensin II on insulin sensitivity and glucose tolerance, we developed B6 mice (UT2-mice) that over-expressed UT2 in mice liver by the administration of adenovirus vector containing UT2 via tail veins, and investigate glucose intolerance and insulin sensitivity as compared with the B6 mice (LacZ-mice) that over-expressed LacZ in liver by the application of adenovirus vector containing LacZ.
We found a significant improvement of insulin sensitivity and glucose tolerance in UT2-mice, as compared with LacZ-mice. Then, we developed B6 mice (GPR14-mice) that over-expressed GPR14 in mice liver by the Ladministration of adenovirus vector containing GPR14. We also confirmed a significant improvement of insulin sensitivity and glucose tolerance in UT2-mice, as compared with LacZ-mice. We concluded that the activation of urorensin II signaling in liver contributed to the improvement of insulin sensitivity and glucose tolerance.
There were accumulating evidence suggesting that the signaling of parasympathetic nerve to NO regulates insulin signaling on glycogen synthesis, gluconeogenesis, lipogenesis and anti-lipolysis. We confirmed the enhanced signaling pathway of parasympathetic nerve to NO in UT2-mice and GPR14-mice, as compared with LacZ-mice. Thus, this investigation clearly demonstrated that signaling defects of urotensin II, parasympathetic nerve to NO might be one of pathogenic mechanisms of insulin resistance and diabetes.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (17 results)

All 2007 2006 2005

All Journal Article (17 results)

  • [Journal Article] Efficient and controlled gene expression in mouse pancreatic islets by arterial delivery of tetracycline-inducible adenoviral vectors.2007

    • Author(s)
      Takahashi R, Ishihara H, et al.
    • Journal Title

      J Mol Endocrinol. 38・1

      Pages: 127-136

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Increased hepatic expression of ganglioside-specific sialidase, NEU3, improves insulin sensitivity and glucose tolerance in mice.2007

    • Author(s)
      Yoshizumi S, Suzuki S, et al.
    • Journal Title

      Metabolism 56・3

      Pages: 420-439

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Efficient and controlled gene expression in mouse pancreatic islets by arterial delivery of tetracycline-inducible adenoviral vectors.2007

    • Author(s)
      Takahashi R, Ishihara H, et al.
    • Journal Title

      J Mol Endocrinol 38・1

      Pages: 127-136

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cell type-specific activation of metabolism reveals that beta-cell secretion suppresses glucagon release from alpha-cells in rat pancreatic islets.2006

    • Author(s)
      Takahashi R, Ishihara H, et al.
    • Journal Title

      Am J Physiol Endocrinol Metab 290・2

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] WFS1-deficiency increases endoplasmic reticulum stress, impairs cell cycle progression and triggers the apoptotic pathway specifically in pancreatic beta-cells.2006

    • Author(s)
      Yamada T, Ishihara H, et al.
    • Journal Title

      Hum Mol Genet. 15・10

      Pages: 1600-1609

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Hypoglycemia associated with hyperinsulinemia in a subject with type 2 diabetes and liver cirrhosis.2006

    • Author(s)
      Tamura A, Ishihara H, et al.
    • Journal Title

      Nippon Naika Gakkai Zasshi 95・7

      Pages: 1371-1374

    • NAID

      10018198589

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] WFS1 protein modulates the free Ca(2+) concentration in the endoplasmic reticulum.2006

    • Author(s)
      Takei D, Ishihara H, et al.
    • Journal Title

      FEBS Lett. 580・24

      Pages: 5635-5640

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] WFS1-deficiency increases endoplasmic reticulum stress, impairs cell cycle progression and triggers the apoptotic pathway specifically in pancreatic beta-cells.2006

    • Author(s)
      Yamada T, Ishihara H, et al.
    • Journal Title

      Hum Mol Genet 15・10

      Pages: 1600-1609

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Hypoglycemia associated with hyperinsulinemia in a subject with type 2 diabetes and liver cirrhosis.2006

    • Author(s)
      Tamura A, Ishihara H, et al.
    • Journal Title

      Nippon Naika Gakkai Zasshi 95.7

      Pages: 1371-1374

    • NAID

      10018198589

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] WFS1 protein modulates the free Ca(2+) concentration in the endoplasmic reticulum.2006

    • Author(s)
      Takei D, Ishihara H, et al.
    • Journal Title

      FEBS Lett 580・24

      Pages: 5635-5640

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] WFS 1-deficiency increases endoplasmic reticulum stress, impairs cell cycle progression and triggers the apoptotic pathway specifically in pancreatic beta-cells.2006

    • Author(s)
      Yamada T, Ishihara H, et al.
    • Journal Title

      Hum Mol Genet. 15・10

      Pages: 1600-1609

    • Related Report
      2006 Annual Research Report
  • [Journal Article] WFSI protein modulates the free Ca(2+) concentration in the endoplasmic reticulum.2006

    • Author(s)
      Takei D, Ishihara H, et al.
    • Journal Title

      FEBS Lett. 580・24

      Pages: 5635-5640

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cell type-specific activation of metabolism reveals that beta-cell secretion suppresses glucagon release from alpha-cells in rat pancreatic islets.2006

    • Author(s)
      Takahashi R, Ishihara H, Ct al.
    • Journal Title

      Am J Physiol Endocrinol Metab 290・2

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Disruption of the WFS1 gene in mice causes progressive beta-cell loss and impaired stimulus-secretion coupling in insulin secretion.2005

    • Author(s)
      Ishihara H, Takeda S, et al.
    • Journal Title

      Hum Mol Genet. 13・11

      Pages: 1159-1170

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Dissipating excess energy stored in the liver is a potential treatment strategy for diabetes associated with obesity.2005

    • Author(s)
      Ishigaki Y, Ishihara H, et al.
    • Journal Title

      Diabetes 54・2

      Pages: 322-332

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Constitutively active PDX1 induced efficient insulin production in adult murine liver.2005

    • Author(s)
      Imai J, Katagiri H, et al.
    • Journal Title

      Biochem Biophys Res Commun 326・2

      Pages: 402-409

    • Related Report
      2005 Annual Research Report
  • [Journal Article] WRN gene 1367 Arg allele protects against development of type 2 diabetes mellitus.2005

    • Author(s)
      Hirai M, Suzuki S, Hinokio Y, et al.
    • Journal Title

      Diabetes Res Clin Pract 69・3

      Pages: 287-292

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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