Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2014) 35 P341 | DOI: 10.1530/endoabs.35.P341

ECE2014 Poster Presentations Diabetes (epidemiology, pathophysiology) (63 abstracts)

Exenatide protects pancreatic islets against brain death-induced inflammation and viability loss

Rodrigo Carlessi 1, , Ana Luiza Dias 1 , Andrea Bauer 1 , Luis Henrique Canani 1, , Cristiane Leitao 2 & Daisy Crispim 1,

1Hospital de Clinicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil; 2Post-Graduation Program in Medical Sciences: Endocrinology, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.

Introduction: Pancreatic islet transplantation is an attractive approach to re-establish glycemic homeostasis in patients with brittle type 1 diabetes. However, islet damage along the isolation procedure limits the availability of viable islets for transplantation. The donor’s brain death (BD) is among the factors contributing for islet quality loss in this scenario. Exenatide, a glucagon-like peptide-1 (GLP1) analog, exerts anti-inflammatory effects leading to an increase in islet cell viability in vitro. Here, we hypothesize that this drug could alleviate the damage caused by BD on pancreatic islets, thus improving the quality of such islets for transplantation. We proposed a study in a murine model of BD in which the administration of Exenatide was evaluated in respect to islet quality parameters.

Methods: Animals were separated into three groups: Sham, BD, and BD plus Exenatide 5 μg/kg (EXE). Islet viability was determined by FDA/PI assay, and gene expressions of IL-1β and Bcl-2 were assessed by RT-qPCR.

Results: A striking viability reduction was observed in islets isolated from the BD group vs sham and EXE groups (59.8±15.5% vs 88.6±4.8 vs 91.6±0.6; P=0.011). Furthermore, a robust and significant increase in IL-1β gene expression was seen in the pancreatic tissue of animals from BD group (17.5±12.1 vs 1.9±1.7 vs 1.9±2.6 arbitrary units (AU), P=0.012). Our data also suggest a greater expression of Bcl-2 in islets originated from the BD group (1.36±0.12 vs 1.0±0.25 vs 0.93±0.28 AU; P=0.11). Although this difference was not formally statistic, it suggests a compensatory effect to counteract the excessive cell death induction in islets originated from the BD group.

Conclusion: Our data indicate an increase in the inflammatory state as well as a reduction in the cell viability of islets isolated from the BD group. Exenatide administration following the establishment of the BD seems to protect the islets against such deleterious effects.

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