The influence of genetic background on the induction of oxidative stress and impaired insulin secretion in mouse islets

Zraika, S., Aston-Mourney, K., Laybutt, D. R., Kebede, M., Dunlop, M. E., Proietto, J. and Andrikopoulos, S. 2006, The influence of genetic background on the induction of oxidative stress and impaired insulin secretion in mouse islets, Diabetologia, vol. 49, no. 6, pp. 1254-1263.

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Title The influence of genetic background on the induction of oxidative stress and impaired insulin secretion in mouse islets
Author(s) Zraika, S.
Aston-Mourney, K.
Laybutt, D. R.
Kebede, M.
Dunlop, M. E.
Proietto, J.
Andrikopoulos, S.
Journal name Diabetologia
Volume number 49
Issue number 6
Start page 1254
End page 1263
Total pages 10
Publisher Springer
Place of publication Heidelberg, Germany
Publication date 2006
ISSN 0012-186X
1432-0428
Keyword(s) anti-oxidants
glucosamine
glucose-stimulated insulin secretion
glucose toxicity
hexosamine biosynthesis pathway
oxidative stress
Summary Aims/hypothesis 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.

Materials and methods 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.

Results 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.

Conclusions/interpretation 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.
Language eng
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2006, Springer-Verlag
Persistent URL http://hdl.handle.net/10536/DRO/DU:30047461

Document type: Journal Article
Collection: School of Medicine
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