Dataset Information

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

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, glucose-stimulated 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.

SUBMITTER: Pi J

PROVIDER: S-EPMC2703519 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Pi Jingbo J Bai Yushi Y Daniel Kiefer W KW Liu Dianxin D Lyght Otis O Edelstein Diane D Brownlee Michael M Corkey Barbara E BE Collins Sheila S

Endocrinology 20090226 7

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 Ucp ...[more]

PMID: 19246534

Similar Datasets

Project description:BackgroundObesity and diabetes mellitus are associated with an increased risk of pancreatic cancer. These associations may be secondary to consequences of peripheral insulin resistance, pancreatic β-cell dysfunction, or hyperglycemia itself. Hemoglobin A1c (HbA1c) is a measure of hyperglycemia, whereas plasma insulin and proinsulin are markers of peripheral insulin resistance, and the proinsulin to insulin ratio marks pancreatic β-cell dysfunction.MethodsThis was a prospective, nested case-control study of 449 case patients and 982 control subjects with prediagnostic blood samples and no diabetes history from five prospective US cohorts followed through 2008. Two or three control subjects were matched to each case patient by year of birth, cohort, smoking, and fasting status. Pancreatic cancer risk was assessed by prediagnostic HbA1c, insulin, proinsulin, and proinsulin to insulin ratio with multivariable-adjusted logistic regression. All P values were two-sided.ResultsThe highest vs lowest quintiles of HbA1c, insulin, and proinsulin were associated with with an increased risk for pancreatic cancer (odds ratio [OR] = 1.79; 95% confidence interval [CI] = 1.17 to 2.72, P trend = .04 for HbA1c; OR = 1.57; 95% CI = 1.08 to 2.30; Ptrend = .002 for insulin; and OR = 2.22; 95% CI = 1.50 to 3.29; P trend < .001 for proinsulin). Proinsulin to insulin ratio was not associated with pancreatic cancer risk. Results were similar across studies (all P heterogeneity > .29). In cancers developing 10 or more years after blood collection, the associations with insulin and proinsulin became stronger (highest vs lowest quintile, OR = 2.77; 95% CI = 1.28 to 5.99 for insulin and OR = 3.60; 95% CI = 1.68 to 7.72 for proinsulin). In mutually adjusted models including HbA1c, insulin, and proinsulin, only proinsulin remained statistically significant ( highest vs lowest quintile, OR = 2.55; 95% CI = 1.54 to 4.21; Ptrend < .001).ConclusionsAmong participants from five large prospective cohorts, circulating markers of peripheral insulin resistance, rather than hyperglycemia or pancreatic β-cell dysfunction, were independently associated with pancreatic cancer risk.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets