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Intracellular calcium signaling of pancreatic B cell and its deterioration in diabetes mellitus.

Research Project

Project/Area Number 09671042
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内分泌・代謝学
Research InstitutionKagawa Medical University (1998)
Hamamatsu University School of Medicine (1997)

Principal Investigator

TAMINATO Tomohiko  Kanagawa Medical University, Dept.of Laboratory Medicine, Professor, 医学部, 教授 (90107954)

Co-Investigator(Kenkyū-buntansha) OKI Yutaka  Hamamatsu University School of Medicine, The second Dept.of Medicine, Research A, 医学部, 助手 (20169204)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsInsulin secretion / Diabetes mellitus / CD38 / ADP-ribosyl cyclase / Cyclic ADP-ribose / CD38 antibody / D-glucose / Intracellular calcium ([Ca2+]i)
Research Abstract

The present study was aimed to clarify the role of CD38 antigen (ADP-ribosyl cyclase) in insulin secretion and its early deterioration of in diabetes mellitus. CD38 antigen catalyzes NAD to produce cyclic ADP-ribose, a novel intracellular calcium-mobilizing substance. We carried out the experiments using anti-CD38 antibody to find the role of CD38 on insulin release from Min 6 cells, a clonal pancreatic B cells. Pretreatment of anti CD38 antibody caused dose-related inhibition of D-glucose-induced insulin release from Min 6 cells. The antibody also inhibited insulin release elicited by D-mannose, L-arginine, a-KIC, carbamylcholine, glucagon, forskolin, and dibutyryl cyclic AMP.The rise of [Ca2+]i in response to glucose or carbamylcholine was significantly inhibited by the pretreatment of anti-CD38 antibody, whereas [Ca2+]i in response to glibenclamide was augmented. In NOD mice, a n animal model of insulin-dependent diabetes mellitus, anti-CD38 antibody was detected with high prevalence.
These results clearly indicate a crucial significance of CD38-cyclic ADP-ribose system in signal transduction in insulin secretion, and moreover, an autoantibody, as shown in NOD mice, may play an important role in the pathogenesis of diabetes.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] 田港朝彦: "Glucagon-like peptide-1(GLP-1)受容体遺伝子。" 糖尿病1. 日本臨床社刊. 432-436 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 田港朝彦: "Fatty acid binding protein-2(FABP-2)遺伝子。" 糖尿病1. 日本臨床社刊. 437-441 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 田港朝彦: "CD38(ADP-ribosyl cyclase)とインスリン分泌。" 糖尿病2. 日本臨床社刊. 880-887 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] RydzewskiA: "Diurnal variation in serum remnant-like lipoproteins, platelet aggregation and fibrinolysis in healthy volunteers" Haemostasis27. 305-314 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Taminato T: "CD38 antigen (ADP-ribosyl cyclase) and Secretory mechanism of insulin secretion. (in Japanese)" Nippon Rinsho. 55 (suppl). 880-87 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Taminato T: "Glucagon-like peptide-1 (GLP-1) receptor gene (in Japanese)" Nippon Rinsho. 55 (suppl). 432-36 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Taminato T: "Fatty acid binding protein-2 (FABP-2) gene (in Japanese)" Nippon Rinsho. 55 (suppl). 437-41 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Rydzewski A: "Diurnal variation in serum remnant-like lipoproteins, platelet aggregation and fibrinolysis in healthy volunteers" Haemostasis. 27. 305-14 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 田港朝彦: "Glucagon-like peptide-1(GLP-1)受容体遺伝子" 糖尿病1.日本臨床社刊. 432-436 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 田港朝彦: "Fatty acid binding protein-2(FABP-2)遺伝子" 糖尿病1.日本臨床社刊. 437-441 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 田港朝彦: "CD38(ADP-ribosyl cyclase)とインスリン分泌" 糖尿病2.日本臨床社刊. 880-887 (1997)

    • Related Report
      1998 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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