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Development of effective methods of islet transplantation for severe diabetes mellitus.

Research Project

Project/Area Number 10671188
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionShimane Medical University

Principal Investigator

TAMURA Katsuhiro  Shimane Med. Univ. 1st Dept. of Surg. Professor, 医学部, 教授 (80155259)

Co-Investigator(Kenkyū-buntansha) YANO Seiji  Shimane Med. Univ. 1st Dept. of Surg. Lecturer, 医学部, 講師 (10220203)
SUMI Shoichiro  Shimane Med. Univ. 1st Dept. of Surg. Lecturer, 医学部, 講師 (80252906)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordsislet of Langerhans transplantation / VEGF / PECAM-1 / CD-31 / factor VIII-related antigen / angiogenesis / glucose tolerance / TNP-470
Research Abstract

1. Islets of Langerhans were isolated from Lewis rats and transplanted to the same descent rats at either subcutaneous tissue (SCT), liver via the portal vein or subnephrocapsular space (SNCS). Up to 4 weeks after transplantation, insulin staining showed viable islets at the liver and SNCS but not at SCT.
2. Normal rat pancreas, islets of Langerhans immediately after isolation, and transplanted islets either at the liver or SNCS were immunostained for vascular endothelial growth factor (VEGF) after trypsin treatment. Islets in the normal pancreas and immediately after isolation were positively stained but those at transplantation (Tx) sites tended to be VEGF-negative. On the other hand, VEGF-staining after microwave treatment showed positive results even in the islets at Tx sites, suggesting that VEGF still exists after Tx. A marker for blood vassels, factor VIII-related antigen (vWF), and specific marker for neogeneic vessels, platelet endothelial cell adhesion molecule-1 (PECAM-1/CD-31) were similarly immunostained. PECAM-1 was not stained in the islets of normal pancreas but became positively stained in those at Tx sites, whereas vWF was stained in normal and transplanted islets.
3. Effects of an anti-neovascularization agent, TNP-470, were examined in islet-transplanted streptozotocin (STZ)-diabetic rats. Administered of TNP-470 did not altered blood glucose levels either at fed state or during oral glucose tolerance test. However, it abolished plasma insulin increase in response to oral glucose challenge, which was observed in normal rats and islet-transplanted STZ-rats without TNP-470 treatment. Histological examination revealed vessel-like tubular structures, which lack PECAM-1-positive endothelial layer.
These results suggest that neovascularization can be evoked from transplanted islets and that neovascularization-promoting treatment may improve the function of transplanted islets.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (7 results)

All Other

All Publications (7 results)

  • [Publications] 渡部広明、他: "ラット移植膵ラ島におけるVascular endothelial growth factor(VEGF)の免疫組織学的検討"膵臓、日本膵臓学会誌. 13. 467-472 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hiroaki Watanabe, et al.: "Immunohistochemical studies on vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule-1/C-31 (PECAM-1) in islet transplantation"Pancreas. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Watanabe H, Sumi S, Yano S, Nio Y, Tamura K.: "Immunohistochemical staining of vascular endothelial growth factor (VEGF) in transplanted islets in rats"Journal of the Japan Pancreas Society. 13. 467-472 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Watanabe H, Sumi S, Urushihata T, Kitamura Y, Iwasaki S, Xu G, Yano S, Nio Y, Tamura K.: "Immunohistochemical studies on vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule-1/CD-31 (PECAM-1) in islet transplantation"Pancreas. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 渡部広明、他: "ラット移植膵ラ島におけるVascular endothelial growth factor(VEGF)の免疫組織学的検討"膵臓、日本膵臓学会誌. 13. 467-472 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hiroaki Watanabe,et al.: "Immunohistochemical studies on vascular endothelial trowth factor(VEGF)and platelet endothelial cell adhesion molecule-1/CD-31(PECAM-1)in islet transplantation."Pancreas. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] 渡部広明、他: "ラット移植膵ラ島におけるVascular endothelial growth factor(VEGF)の免疫組織学的検討" 膵臓、日本膵臓学会誌. 13. 467-472 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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