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Title: The influence of genetic background on the induction of oxidative stress and impaired insulin secretion in mouse islets.
Austin Authors: Zraika, S;Aston-Mourney, Kathryn;Laybutt, D R;Kebede, M;Dunlop, Mark E;Proietto, Joseph ;Andrikopoulos, Sofianos
Affiliation: Department of Medicine (AH/NH), University of Melbourne, Heidelberg Repatriation Hospital, Heidelberg Heights, VIC 3081, Australia
Issue Date: 29-Mar-2006
Publication information: Diabetologia 2006; 49(6): 1254-63
Abstract: We determined whether high-glucose-induced beta cell dysfunction is associated with oxidative stress in the DBA/2 mouse, a mouse strain susceptible to islet failure.Glucose- and non-glucose-mediated insulin secretion from the islets of DBA/2 and control C57BL/6 mice was determined following a 48-h exposure to high glucose. Flux via the hexosamine biosynthesis pathway was assessed by determining O-glycosylated protein levels. Oxidative stress was determined by measuring hydrogen peroxide levels and the expression of anti-oxidant enzymes.Exposure to high glucose levels impaired glucose-stimulated insulin secretion in DBA/2 islets but not C57BL/6 islets, and this was associated with reduced islet insulin content and lower ATP levels than in C57BL/6 islets. Exposure of islets to glucosamine for 48 h mimicked the effects of high glucose on insulin secretion in the DBA/2 islets. High glucose exposure elevated O-glycosylated proteins; however, this occurred in islets from both strains, excluding a role for O-glycosylation in the impairment of DBA/2 insulin secretion. Additionally, both glucosamine and high glucose caused an increase in hydrogen peroxide in DBA/2 islets but not in C57BL/6 islets, an effect prevented by the antioxidant N-acetyl-L: -cysteine. Interestingly, while glutathione peroxidase and catalase expression was comparable between the two strains, the antioxidant enzyme manganese superoxide dismutase, which converts superoxide to hydrogen peroxide, was increased in DBA/2 islets, possibly explaining the increase in hydrogen peroxide levels.Chronic high glucose culture caused an impairment in glucose-stimulated insulin secretion in DBA/2 islets, which have a genetic predisposition to failure, and this may be the result of oxidative stress.
Gov't Doc #: 16570159
DOI: 10.1007/s00125-006-0212-9
Journal: Diabetologia
Type: Journal Article
Subjects: Adenosine Triphosphate.metabolism
Cell Culture Techniques
Cell Survival
DNA Primers
Gene Expression Regulation
Hydrogen Peroxide.analysis
Islets of Langerhans.cytology.drug effects.secretion
Mice, Inbred C57BL
Mice, Inbred DBA.genetics
Oxidative Stress.genetics
Polymerase Chain Reaction.methods
Appears in Collections:Journal articles

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