TY - JOUR
T1 - Persistent oxidative stress due to absence of uncoupling protein 2 associated with impaired pancreatic β-cell function
AU - Pi, Jingbo
AU - Bai, Yushi
AU - Daniel, Kiefer W.
AU - Liu, Dianxin
AU - Lyght, Otis
AU - Edelstein, Diane
AU - Brownlee, Michael
AU - Corkey, Barbara E.
AU - Collins, Sheila
PY - 2009/7
Y1 - 2009/7
N2 - Uncoupling protein (UCP) 2 is a widely expressed mitochondrial protein whose precise function is still unclear but has been linked to mitochondria-derived reactive oxygen species production. Thus, the chronic absence of UCP2 has the potential to promote persistent reactive oxygen species accumulation and an oxidative stress response. Here, we show that Ucp2-/- mice on three highly congenic (N >10) strain backgrounds (C57BL/6J, A/J, 129/SvImJ), including two independently generated sources of Ucp2-null animals, all exhibit increased oxidative stress. Ucp2-null animals exhibit a decreased ratio of reduced glutathione to its oxidized form in blood and tissues that normally express UCP2, including pancreatic islets. Islets from Ucp2-/-mice exhibit elevated levels of numerous antioxidant enzymes, increased nitrotyrosine and F4/80 staining, but no change in insulin content. Contrary to results in Ucp2-/- mice of mixed 129/B6 strain background, glucosestimulated insulin secretion in Ucp2-/- islets of each congenic strain was significantly decreased. These data show that the chronic absence of UCP2 causes oxidative stress, including in islets, and is accompanied by impaired glucose-stimulated insulin secretion.
AB - Uncoupling protein (UCP) 2 is a widely expressed mitochondrial protein whose precise function is still unclear but has been linked to mitochondria-derived reactive oxygen species production. Thus, the chronic absence of UCP2 has the potential to promote persistent reactive oxygen species accumulation and an oxidative stress response. Here, we show that Ucp2-/- mice on three highly congenic (N >10) strain backgrounds (C57BL/6J, A/J, 129/SvImJ), including two independently generated sources of Ucp2-null animals, all exhibit increased oxidative stress. Ucp2-null animals exhibit a decreased ratio of reduced glutathione to its oxidized form in blood and tissues that normally express UCP2, including pancreatic islets. Islets from Ucp2-/-mice exhibit elevated levels of numerous antioxidant enzymes, increased nitrotyrosine and F4/80 staining, but no change in insulin content. Contrary to results in Ucp2-/- mice of mixed 129/B6 strain background, glucosestimulated insulin secretion in Ucp2-/- islets of each congenic strain was significantly decreased. These data show that the chronic absence of UCP2 causes oxidative stress, including in islets, and is accompanied by impaired glucose-stimulated insulin secretion.
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U2 - 10.1210/en.2008-1642
DO - 10.1210/en.2008-1642
M3 - Article
C2 - 19246534
AN - SCOPUS:67649641804
SN - 0013-7227
VL - 150
SP - 3040
EP - 3048
JO - Endocrinology
JF - Endocrinology
IS - 7
ER -