Endocrine Abstracts

Introduction: Long-term insulin independence after pancreatic islet transplantation depends on the engraftment of a large number of viable islets. However, the yield and quality of islets isolated from brain-death (BD) donors are negatively affected by upregulation of proinflammatory cytokines and by hypoxia and oxidative stress that occurs during the BD status. Uncoupling proteins (UCPs) are mitochondrial transporters present in the inner mitochondrial membrane and are associated with protection against oxidative stress. Manganese superoxide dismutase (MnSOD) enzyme is the first line of defense against oxidative stress in mitochondria. Thus, we compared pancreatic gene expressions of UCP1, UCP2 and MnSOD between BD-organ donors and control subjects who undergone therapeutic pancreatectomy. The expressions of these genes were also evaluated in a murine model of BD.

Methods: Human pancreatic tissue biopsies were collected from 15 cases of BD and 17 controls, while rat pancreatic biopsies were obtained from 7 BD rats and 6 controls. Pancreatic UCP1, UCP2 and MnSOD gene expressions were evaluated by RT-qPCR.

Results: Brain-death organ donors had higher pancreatic mRNA concentrations of UCP1 and UCP2 in comparison to control subjects (UCP1: 0.55±0.54 vs −0.38±0.52 n fold change (P=0.001); UCP2: 0.36±0.20 vs −0.39±0.81 (P=0.012)). Accordingly, pancreatic Ucp2 mRNA concentrations were higher in BD rats than in control rats (0.41±0.22 vs 0.04±0.21 (P=0.013)). Ucp1 mRNA was not detected in the murine pancreas. Human MnSOD mRNA levels were similar in pancreas from BD cases and controls; however, murine Mnsod expression was higher in the pancreas of BD rats compared to controls (0.15±0.32 vs −0.22±0.32; P=0.037).

Conclusion: UCP1-2 expressions seem to be affected by BD of organ donors. Further studies are necessary to evaluate the role of these proteins in the modulation of BD-induced oxidative stress in the pancreas.