Porcine marginal mass islet autografts resist metabolic failure over time and are enhanced by early treatment with liraglutide

Juliet A. Emamaullee, Shaheed Merani, Christian Toso, Tatsuya Kin, Faisal Al-Saif, Wayne Truong, Rena Pawlick, Joy Davis, Ryan Edgar, Jennifer Lock, Susan Bonner-Weir, Lotte B. Knudsen, A. M.James Shapiro

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37 Scopus citations


Although insulin independence is maintained in most islet recipients at 1 yr after transplant, extended follow-up has revealed that many patients will eventually require insulin therapy. Previous studies have shown that islet autografts are prone to chronic failure in large animals and humans, suggesting that nonimmunological events contribute to islet graft functional decay. Early intervention with therapies that promote graft stability should provide a measurable benefit over time. In this study, the efficacy of the long-acting glucagon-like peptide-1 analog liraglutide was explored in a porcine marginal mass islet autograft transplant model. Incubation with liraglutide enhanced porcine islet survival and function after prolonged culture. Most vehicle-treated (83%) and liraglutide-treated (80%) animals became insulin independent after islet autotransplantation. Although liraglutide therapy did not improve insulin independence rates or blood glucose levels after transplant, a significant increase in insulin secretion and acute-phase insulin response was observed in treated animals. Surprisingly, no evidence for deterioration of graft function was observed in any of the transplanted animals over more than 18 months of follow-up despite significant weight gain; in fact, an enhanced response to glucose developed over time even in control animals. Histological analysisshowedthat intraportallytransplanted islets remained highly insulin positive, retained a-cells, and did not form amyloid deposits. This study demonstrates that marginal mass porcine islet autografts have stable long-term function, even in the presence of an increasing metabolic demand. These results are discrepant with previous large animal studies and suggestthat porcine islets may be resistantto metabolicfailure.

Original languageEnglish (US)
Pages (from-to)2145-2152
Number of pages8
Issue number5
StatePublished - May 2009
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology


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