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, doi: 10.1007/s00125-006-0212-9.

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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.ORCID iD for 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
Keyword(s) anti-oxidants
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
DOI 10.1007/s00125-006-0212-9
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
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Document type: Journal Article
Collection: School of Medicine
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