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Author Notes:

Address correspondence to: Shanthi Srinivasan, Division of Digestive Diseases, Emory University, Whitehead Research Building, Suite 246, 615 Michael Street, Atlanta, GA 30307 Tel: 404-727-5298; Fax: 404-727-5767; ssrini2@emory.edu

Subject:

Research Funding:

This work was supported by the following grants: NIH-RO1 DK080684 (S. Srinivasan), Juvenile Diabetes Foundation (26-2008-878, S. Srinivasan), VA MERIT award (S. Srinivasan) and DDRDC DK064399 (S. Srinivasan).

Keywords:

  • Islet transplantation
  • diabetes
  • GDNF
  • islet survival
  • normoglycemia

Glial cell line-derived neurotrophic factor enhances human islet posttransplantation survival

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Journal Title:

Transplantation

Volume:

Volume 92, Number 7

Publisher:

, Pages 745-751

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Background Development of pre-transplantation islet culture strategies that preserve or enhance β-cell viability would eliminate the requirement for the large numbers of islets needed to restore insulin independence in type 1 diabetes patients. We investigated whether glial cell line-derived neurotrophic factor (GDNF) could improve human islet survival and post-transplantation function in diabetic mice. Methods Human islets were cultured in medium supplemented with or without GDNF (100 ng/ml) and in vitro islet survival and function assessed by analyzing β-cell apoptosis and glucose stimulated insulin release. In vivo effects of GDNF were assessed in streptozotocin-induced diabetic nude mice transplanted under the kidney capsule with 2000 islet equivalents of human islets pre-cultured in medium supplemented with or without GDNF. Results In vitro, human islets cultured for 2–10 days in medium supplemented with GDNF showed lower β-cell death, increased Akt phosphorylation and higher glucose-induced insulin secretion than islets cultured in vehicle. Human islets pre-cultured in medium supplemented with GDNF restored more diabetic mice to normoglycemia and for a longer period after transplantation than islets cultured in vehicle. Conclusions Our study shows that GDNF has beneficial effects on human islet survival and could be used to improve islet post-transplantation survival.

Copyright information:

© 2011 Lippincott Williams & Wilkins, Inc.

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