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2007 Fiscal Year Final Research Report Summary

Search for novel mechanisms of insulin secretion by combination of proteom analysis and HPLC

Research Project

Project/Area Number 17590956
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionShinshu University

Principal Investigator

KOMATSU Mitsuhisa  Shinshu University, 大学院・医学系研究科, Associate Professor (90221978)

Co-Investigator(Kenkyū-buntansha) KABURAGI Yasushi  International Medical Center of Japan, Department of Metabolic Disorder, Director (40342927)
NODA Mitsuhiko  International Medical Center of Japan, Director (90237850)
AIZAWA Toru  Shinshu University, 医学部, Professor (90150896)
Project Period (FY) 2005 – 2007
Keywordsinsulin release / secretion / acvlation / proteosome / type 2 diabetes / branched-chian amino acids
Research Abstract

Insulin release from pancreatic B-cell is regulated by multiple distinct mechanisms, which are mutually related. Among various insulin secretagogues, glucose is the most powerful and important one. Glucose is known to stimulate insulin release via KATP channel-dependent and -independent mechanisms. Molecular basis for the KATP channel-dependent mechanism has relatively well established. Our research purpose is, therefore, to elucidate the mechanisms of KATP channel-independent pathways. During this research project, we first identify two distinct proteins that are palmitoylated in the pancreatic B-cell by using two-dimensional gel electrophoresis. This was confirmed by proteom analysis; aminoacid sequence analysis revealed that they were cofilin and destrin. In pancreatic B-cell lines, cofilin and destrin were successfully knocked down by the respective siRNA. However, glucose-stimulated insulin release was not attenuated by these treatments. Thus, functional importance of the two proteins remained unknown. As a next step to approach the physiological importance of protein palmitoylation, we established a novel method to detect palmitoylated proteins specifically. By using this new technique, we are currently trying to identify newer player in the stimulus-secretion coupling in pancreatic B-cell. In another aspect of our achievement is that branch-amino acids significantly lower plasma glucose in diabetic animals. We also obtained preliminary results suggesting the branched-chain amino acid exhibit insulinotropic action via previously unknown mechanisms. In future, we will approach to mechanisms of impaired insulin secretion in patients with type 2 diabetes by extending our knowledge of the mechanisms of insulin secretion.

  • Research Products

    (9 results)

All 2008 2007 2006 2005

All Journal Article (6 results) (of which Peer Reviewed: 3 results) Presentation (2 results) Book (1 results)

  • [Journal Article] Acute and chronic treatment of L-isoleucine ameliorates glucose metabolism inglucose-intolerant and diabetic mice.2008

    • Author(s)
      Ikehara O, Kawasaki N, Maezono K, Komatsu M, Konishi A
    • Journal Title

      Biol Pharm Bull 31

      Pages: 469-472

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Acute and chronic treatment of L-isoleucine ameliorates glucose metabolism in glucose-intolerant and diabetic mice2008

    • Author(s)
      Ikehara, 0., Kawasaki, N., Maezono, K., Komatsu, M., Konishi, A
    • Journal Title

      Biol Pharm Bull 31

      Pages: 469-472

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Adiponectin Inversely Correlates with High Sensitive C-reactive Protein and Triglycerides, but not with Insulin Sensitivity, in Apparently Healthy Japanese Men.2007

    • Author(s)
      Komatsu M, Ohfusa H, Aizawa T, Hashizume K
    • Journal Title

      Endocr J 54

      Pages: 553-558

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Adiponectin Inversely Correlates with High Sensitive C-reactive Protein and Triglycerides, but not with Insulin Sensitivity, in Apparently Healthy Japanese Men2007

    • Author(s)
      Komatsu, M., Ohfusa, H., Aizawa, T., Hashizume, K
    • Journal Title

      Endocr J 54

      Pages: 553-558

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Rab27a: a new face in beta cell metabolism-secretion coupling.2005

    • Author(s)
      Aizawa T, Komatsu M
    • Journal Title

      J Clin Invest 115

      Pages: 227-230

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Rab27a : a new face in beta cell metabolism-secretion coupling2005

    • Author(s)
      Aizawa, T., Komatsu, M
    • Journal Title

      J Clin Invest 115

      Pages: 227-230

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Adiponectin inversely correlates with triglyceride and high-sensitivity C-reactive protein butnot with insulin or insulin resistance index in Japanese men.2006

    • Author(s)
      Komatsu M, Ohfusa H, Aizawa T, Hashizume K
    • Organizer
      19th World Diabetes Congress
    • Place of Presentation
      Cape Town, South Africa
    • Year and Date
      2006-12-05
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Adiponectin inversely correlates with triglyceride and high-sensitivity C-reactive protein but not with insulin or insulin resistance index in Japanese men2006

    • Author(s)
      Komatsu, M., Ohfusa, H., Aizawa, T., Hashizume, K
    • Organizer
      19th World Diabetes Congress
    • Place of Presentation
      Cape Town, South Africa
    • Year and Date
      2006-12-05
    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] Glucose and nutrient-induced increase in insulin secretion in the absence of a rise in[Ca2+]i. In Commentaries on Perspectives in Diabetes2006

    • Author(s)
      Komatsu M, Schermerhorn T, Noda M, Straub SG, Aizawa T, Sharp G
    • Total Pages
      3
    • Publisher
      Robertson RP, Ed., American Diabetes Association
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2010-02-04  

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