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1995 Fiscal Year Final Research Report Summary

Abnomal cytokine expression in diabetes mellitus and diabetic complications, and their treatment by cytokine control

Research Project

Project/Area Number 06670997
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionTohoku University

Principal Investigator

SATOH Jo  Tohoku University, School of Medicinc Lecturer, 医学部附属病院, 講師 (60125565)

Co-Investigator(Kenkyū-buntansha) SATO Yoshinori  Tohoku University, School of Medicine Assistant, 医学部, 助手 (50241633)
MASUDA Takayuki  Department of Medical Technology, College of Medical Science, Tohoku University, 医療技術短期大学部, 教授 (00113910)
Project Period (FY) 1994 – 1995
KeywordsTNFalpha / TNFbeta / NOD mouse / KK-Ag mouse / IDDM / NIDDM / N-acetylcysteine / diabetic neuropathy
Research Abstract

Recently it has been reported that cytokines have a variety of bioactivities in physiological and pathological conditions. As to diabetes mellitus, we have previously reported that development of insulin-dependent diabetes mellitus (IDDM) in NOD mice is significantly inhibited by systemic administration of TNFalpha and TNFbeta, although these are implicated to play pathogenic roles in insulitis lesions. In this study we have further shown various roles of cytokines not only in IDDM but also in non-insulin dependent diabetes mellitus (NIDDM) and diabetic complications.
Systemic administration of recombinant human TNFbeta completely prevented development of IDDM in NOD mice. This suppressive effect of TNFbeta was due to inhibition of anti-islet effector cells in various phases in autoimmunity, e. g., induction and effector phase. Cytokine inducers such as streptococcal preparation (OK-432), BCG and complete Freund's adjuvant (CFA) remarkably improved glucose tolerance in NIDDM animal models. In vivo TNFalpha production was significantly increased in long term hyperglycemic condition in diabetic animals, indicating that TNFalpha might be related to diabetic complications. We found the increased serum levels of TNFalpha in diabetic patients, and that suppression of TNFalpha production with N-acetylcysteine significantly inhibited development of diabetic peripheral neuropathy in streptozotocin-induced diabetic rats. Pentoxifylline, a known TNFalpha inhibitor, had similar beneficial effect on the neuropathy.
Thus, a variety of desirable and undesirable role of cytokines in diabetes and its complications and therapeutic application of cytokine control has been shown in this study.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] K. Takahashi, et et.: "Analysis of mechanism of action of lymphotoxin on prevention of cyclophospnamide-induced diabetes in NOD mice" Journal of Autoimmunity. 8. 335-346 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K. Takahashi, et et.: "Reduced expression of c-FOS in female NOD mouse thymocytes and up-regulation with human lymphotoxin" Cellular Immunology. 164. 287-294 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J, Satoh, et al: "Prevention of autoimmune diabetes in the animal models with TNFα and THFβ" Diabetes 1994. 210-214 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M. Sagara, et al.: "Inhibition with N-acetylcysteine of development of peripheral neuropathy in streptozotocin-induced diabetic rats" Diabetologia. (in press). (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] X. P. Zhu, et al: "Improvement of glucose tolerance with immunomodulators in Type 2 diabetic animals" Biotherapy. (in press). (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M. Sagawa, J. Satoh et al: "Inhibition with N-acetylcysteine of enhanced production of tumor necrosis factor in streptozotocin-induced diabetic rats" Clin. Immunol. Immunopathol. 71. 333-337 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J, Satoh, et al: "Diabetes 1994 (International Congress Series 1100)" Excepta Medica(S.Baba and T.Kaneko, etc), 1270 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sagara M,Satoh J,Zhu X-P,Takahashi K,Fukuzawa M,Muto G,Muto Y,Toyota T: "Inhibition with N-acetylcysteine of enhanced production of tumor necrosis factor in streptozotocin-induced diabetic rats." Clin Immunol Immunopathol. 71. 333-337 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi K,Satoh J,Sagara M,Zhu XP,Muto G,Muto Y,Nishiura S,Miyaguchi S,Toyota T: "Analysis of mechanism of action of lymphotoxin on prevention of cyclophosphamide-induced diabetes in NOD mice." J.Autoimmunity. 8. 335-346 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi K,Satoh J,Sagara M,Muto G,Muto Y,Fukuzawa M,Nishiura S,Miyaguchi S,Qiang XL,Kumagai K,Toyota T: "Reduced expression of c-Fos in female NOD mouse thymocytes and up-regulation with human lymphotoxin." Cell Immunol. 164. 287-294 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Zhu XP,Satoh J,Muto G,Muto Y,Sagara M,Takahashi K,Seino H,Hirai S,Masuda T,Tanaka S,Ishida H,Seino Y, Toyota T: "Improvement of glucose tolerance with immunomodulators in Type2 diabetic animals." Biotherapy. (in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sagara M,Satoh J,Wada R,Yagihashi S,Takahashi K,Fukuzawa M,Muto G,Muto Y,Toyota T: "Inhibition with Nacetylcysteine of development of peripheralneuropathy in streptozotocin-induced diabetic rats." Diabetologia. (in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1997-03-04  

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