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Transplantation. 2017 Mar;101(3):e59-e67. doi: 10.1097/TP.0000000000001292.

UCP2 Expression Is Increased in Pancreas From Brain-Dead Donors and Involved in Cytokine-Induced β Cells Apoptosis.

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1 Endocrine Division, Laboratory of Human Pancreatic Islet Biology, Hospital de Clinicas de Porto Alegre, Porto Alegre, RS, Brazil.2 Post-Graduate Program in Medical Sciences: Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.3 ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles, Brussels, Belgium.



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 β cell apoptosis, but these findings remain controversial.


We have presently performed a case-control study to assess UCP2 expression in pancreas from BD 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.


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.


These data suggest that UCP2 has an apoptotic effect in β cells via regulation of the intrinsic pathway of apoptosis.

[Indexed for MEDLINE]

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