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Journal of Transplantation
Volume 2012, Article ID 382518, 10 pages
http://dx.doi.org/10.1155/2012/382518
Research Article

Exenatide Pretreatment Improved Graft Function in Nonhuman Primate Islet Recipients Compared to Treatment after Transplant Only

1Division of Transplantation, Department of Surgery, 1st Floor, The Ohio State University, 395 West 12th Avenue, Columbus, OH 43210, USA
2Division of Endocrinology, Diabetes and Metabolism, 491 McCampbell Hall, 1581 Dodd Drive, Columbus, OH 43210, USA
3Office of Responsible Research Practices, University Laboratory Animal Resources, The Ohio State University, Columbus, 1960 Kenny Road, OH 43210, USA

Received 15 May 2012; Revised 16 July 2012; Accepted 8 August 2012

Academic Editor: Johan Olerud

Copyright © 2012 Jill L. Buss et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The GLP-1 receptor agonist, exenatide, has previously been shown to improve insulin secretion, protect beta cells from apoptosis, and promote beta cell regeneration. We propose that pretreatment with exenatide will promote islet graft survival and improve graft function. Pancreatectomized cynomolgus monkeys underwent islet allotransplantation and were treated with exenatide beginning on day 0 or day −2. A third group of animals was treated with an immunosuppressive regimen while a fourth group remained untreated. Fasting blood glucose (FBG) was used to evaluate graft function along with intravenous glucose tolerance tests (IVGTTs) performed at study endpoint (day 10 for untreated and posttransplant exenatide or day 90 for pretreatment exenatide and immunosuppression). The average FBG for pre-treated animals day 5 following transplant was  mg/dl, compared to  mg/dl for animals treated only following transplant, 59.4 mg/dl for animals treated with immunosuppression, and  mg/dl for untreated animals. IVGTTs performed at study endpoint showed normal glucose and insulin curves in the pre-treated exenatide and immunosuppression groups only, with beta cell function actually improving after transplant in the pre-treated group. We conclude, therefore, that exenatide pre-treatment can successfully maintain islet graft survival in nonhuman primates.