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Molecular mechanisms of the disruption of immunological tolerance in type 1 diabetes

Research Project

Project/Area Number 12671083
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionHYOGO COLLEGE OF MEDICINE

Principal Investigator

NAMBA Mitsuyoshi  Hyogo College of Medicine, Assoc. Prof., 医学部, 助教授 (00183533)

Co-Investigator(Kenkyū-buntansha) KONYA Hiroyuki  Hyogo College of Medicine, Research Associate, 医学部, 助手 (50340956)
HAMAGUCHI Tomoya  Hyogo College of Medicine, Research Associate, 医学部, 助手 (60330461)
KOHRU Kousuke  Hyogo College of Medicine, Research Associate, 医学部, 助手 (30278832)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsInsulitis / Pancreatic β-cell / Pancreatic biopsy / Betacellulin / Alloxan Dibetes / Fas / NODマウス / 免疫寛容 / 糖尿病
Research Abstract

(1) To explore the efficacy of regenerative approach against the pancreatic /3 -cell in the treatment of human type 1 diabetes, we examined the in vivo effect of recombinant human Betacellulin(BTC) on glucose intolerance and pancreatc morphlogy using a new mouse model with glucose intolerance induced by selective alloxan per fusion. Glucose tolerance was significantly improved and islet-like cell clusters, consisting mainly of $-cells, were increased in the pancreas by 4-weeks subcutaneous injections of ETC.
(2) To better understand the pathogenesis of type 1diabetes, we have developed pancreatic biopsy under laparoscope for recent -onset type 1 diabetic patients. T-cell-predominant infiltration to islets(insulitis) and hyperexpression of major histocompatibility complex clas 1 antigens on islet cells were observed without serious complications. Thus, the pancreatic biopsy under laparoscopy is a safe procedure for detecting in situ autoimmune phenomena in resent-onset type 1 diabeticpatients."

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Yamamoto, K.: "Recombinant human betacellulin promotes neogenesis of β-cells and ameliorates glucose intolerance In mice with diabetes Induced by selective alloxan perfusion"Diabetes. 49・12. 2021-2027 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Iizuka, K.: "Stable overexpression of the glucose-6-phosphatase catalytic subunit attenuates glucose sensitivity of Insulin secretion from a mouse pancreatic beta cell line"J.Endocrinology. 164・3. 307-314 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Imagawa, A.: "Pancreatic biopsy as a procedure for detecting in situ autoimmune phenomena in type 1 diabetes : close correlation between serological markers and histological evidence of cellular autoimununity"Diabetes. 50・6. 1269-1273 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Iizuka, K.: "Metabolic consequence of long-term exposure of pancreatic beta cells to freefatty acid with special reference to glucose Insensitivity"Biochim.Biophys.Acta.. 1586・1. 23-31 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Iwahashi, H.: "Thyroid hormone receptor Interacting protein (Trip3) Is a novel coactivator of hepatocyte nuclear factor-4a (HNF-4a)"Diabetes. 51(In press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K.Yamamoto: "Recombmant numan betacellulin promotes intolerance in mice with diabetes inducedby selective alloxan perfusion."Diabetes. 49. 2021-2027 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A.Imagawa: "Pancreatic biopsy as a procedure for detecting in situ autoimmune phenomena intype 1 diabetes : close correlation between serological markers and histological evidence of cellular autoimununity."Diabetes. 50(6). 1269-1276 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] lizukaK: "Metabolic consequence of lomg term exposure of pancreatic beta cells to free fatty acid with special reference to glucose insensitivlty."Blochimica Biophysica et Acta.. 1586(1). 23-31 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] IwahashiH: "Thyroid hormone receptor interacting protein (Trips) is a novel coactivator of hepatocyte nuclear factor-4a (HNF-4a)."Diabetes. 51(in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamamoto, K.: "Recombinant human betacellulin promotes neogenesis of β -cells and ameliorates glucose intolerance in mice with diabetes induced by selective alloxan perfusion"Diabetes. 49・12. 2021-2027 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Iizuka, K.: "Stable overexpression of the glucose-6-phosphatase catalytic subunit attenuates glucose sensitivity of insulin secretion from a mouse pancreatic beta cell line"J. Endocrinology. 164・3. 307-314 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Imagawa, A.: "Pancreatic biopsy as a procedure for detecting in situ autoimmune phenomena in type 1 diabetes : close correlation between serological markers and histological evidence of cellular autoimununity"Diabetes. 50・6. 1269-1273 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Iizuka, K.: "Metabolic consequence of long-term exposure of pancreatic beta cells to freefatty acid with special reference to glucose insensitivity"Biochim. Biophys. Acta.. 1586・1. 23-31 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Iwahashi, H.: "Thyroid hormone receptor interacting protein (Trip3) is a novel coactivator of hepatocyte nuclear factor-4a (HNF-4a)"Diabetes. 51(In press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamamoto,K.: "Recombinant human betacellulin promotes neogenesis of β-cells and ameliorates glucose intolerance in mice with diabetes induced by selective alloxan perfusion."Diabetes. 49・12. 2021-2027 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Iizuka,K.: "Stable overexpression of the glucose-6-phosphatase catalytic subunit attenuates glucose sensitivity of insulin secretion from a mouse pancreatic beta cell line."J.Endocrinology. 164・3. 307-314 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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