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Scientific article
English

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

Contributors

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

Published in

Endocrinology, vol. 150, no. 5, p. 2145-2152

Publication date

2009

Abstract

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 analysis showed that intraportally transplanted islets remained highly insulin positive, retained alpha-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 suggest that porcine islets may be resistant to metabolic failure.

Keywords

  • Animals
  • Apoptosis/drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Female
  • Glucagon-Like Peptide 1/*analogs & derivatives/pharmacology/therapeutic use
  • Glucose/metabolism
  • Graft Survival/*drug effects/physiology
  • Insulin-Secreting Cells/drug effects/metabolism/physiology/transplantation
  • Islets of Langerhans Transplantation/*methods/rehabilitation/veterinary
  • Metabolic Diseases/*prevention & control
  • Swine
  • Swine, Miniature
  • Time Factors
  • Transplantation, Autologous

UNIGE affiliation entities

UNIGE research groups

Citation (ISO format)

EMAMAULLEE, Juliet A. et al. Porcine marginal mass islet autografts resist metabolic failure over time and are enhanced by early treatment with liraglutide. In: Endocrinology, 2009, vol. 150, n° 5, p. 2145–2152. doi: 10.1210/en.2008-1116

Main files (1)

Article

Identifiers

Additional URL for this publication

http://endo.endojournals.org/content/150/5/2145.full.pdf

Journal ISSN

0013-7227
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Technical informations

Creation

23/04/2012 13:23:30

First validation

23/04/2012 13:23:30

Update

14/10/2025 00:15:30

Status update

14/03/2023 17:24:53

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