Résumé : Background. Systemic inflammation associated with brain death (BD) decreases islet yield and quality, negatively affecting outcomes of human islet transplantation. A recent study from our group showed an increased expression of uncoupling protein-2 (UCP2) in pancreas from rats with BD as compared with controls. UCP2 is located in the mitochondrial inner membrane and regulates production of reactive oxygen species and glucose-stimulated insulin secretion. It has been suggested that UCP2 also plays a role in ? cell apoptosis, but these findings remain controversial.Methods.We have presently performed a case-control study to assessUCP2 expression in pancreas fromBD donors (cases) and subjects who underwent pancreatectomy (controls).We next investigated the role of Ucp2 in cytokine-induced apoptosis of rat insulin-producing INS-1E cells. Results. UCP2 gene expression was higher in pancreas from BD donors compared with controls (1.73 ± 0.93 vs 0.75 ± 0.66; fold change, P < 0.05). Ucp2 knockdown (80% at the protein and messenger RNA levels) reduced by 30% cytokine-induced apoptosis and nitric oxide production in INS-1E cells. This protection was associated with decreased expression of cleaved (activated) caspases 9 and 3, suggesting that Ucp2 knockdown interferes with cytokine triggering of the intrinsic apoptotic pathway. Moreover, both messenger RNA and protein concentrations of the antiapoptotic protein Bcl-2 were increased after Ucp2 knockdown in INS-1E cells. Conclusions. These data suggest that UCP2 has an apoptotic effect in ? cells via regulation of the intrinsic pathway of apoptosis.