Persistent oxidative stress due to absence of uncoupling protein 2 associated with impaired pancreatic β-cell function

Jingbo Pi, Yushi Bai, Kiefer W. Daniel, Dianxin Liu, Otis Lyght, Diane Edelstein, Michael Brownlee, Barbara E. Corkey, Sheila Collins

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)3040-3048
Number of pages9
JournalEndocrinology
Volume150
Issue number7
DOIs
StatePublished - Jul 2009

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Oxidative Stress
Insulin
Reactive Oxygen Species
129 Strain Mouse
Mitochondrial Proteins
Islets of Langerhans
Glutathione
Mitochondria
Antioxidants
Staining and Labeling
Glucose
Enzymes
Uncoupling Protein 2
3-nitrotyrosine

ASJC Scopus subject areas

  • Endocrinology

Cite this

Pi, J., Bai, Y., Daniel, K. W., Liu, D., Lyght, O., Edelstein, D., ... Collins, S. (2009). Persistent oxidative stress due to absence of uncoupling protein 2 associated with impaired pancreatic β-cell function. Endocrinology, 150(7), 3040-3048. https://doi.org/10.1210/en.2008-1642

Persistent oxidative stress due to absence of uncoupling protein 2 associated with impaired pancreatic β-cell function. / Pi, Jingbo; Bai, Yushi; Daniel, Kiefer W.; Liu, Dianxin; Lyght, Otis; Edelstein, Diane; Brownlee, Michael; Corkey, Barbara E.; Collins, Sheila.

In: Endocrinology, Vol. 150, No. 7, 07.2009, p. 3040-3048.

Research output: Contribution to journalArticle

Pi, J, Bai, Y, Daniel, KW, Liu, D, Lyght, O, Edelstein, D, Brownlee, M, Corkey, BE & Collins, S 2009, 'Persistent oxidative stress due to absence of uncoupling protein 2 associated with impaired pancreatic β-cell function', Endocrinology, vol. 150, no. 7, pp. 3040-3048. https://doi.org/10.1210/en.2008-1642
Pi, Jingbo ; Bai, Yushi ; Daniel, Kiefer W. ; Liu, Dianxin ; Lyght, Otis ; Edelstein, Diane ; Brownlee, Michael ; Corkey, Barbara E. ; Collins, Sheila. / Persistent oxidative stress due to absence of uncoupling protein 2 associated with impaired pancreatic β-cell function. In: Endocrinology. 2009 ; Vol. 150, No. 7. pp. 3040-3048.
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