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Enhancement of homocysteine toxicity to insulin-secreting BRIN-BD11 cells in combination with alloxan

Scullion, S. M. J., Gurgul-Convey, E., Elsner, M., Lenzen, S., Flatt, Peter and McClenaghan, Neville (2012) Enhancement of homocysteine toxicity to insulin-secreting BRIN-BD11 cells in combination with alloxan. JOURNAL OF ENDOCRINOLOGY, 214 (2). pp. 233-238. [Journal article]

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DOI: 10.1530/JOE-11-0461


Previous studies have shown that homocysteine (HC) has a detrimental impact on insulin secretion and pancreatic beta cell function. The aim of the present study was to determine the role of reactive oxygen species (ROS) in the in vitro toxic effects of HC on insulin secretion and function of BRIN-BD11 insulin-secreting cells. In this study, insulin secretion from BRIN-BD11 cells was determined radioimmunologically, cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and glucokinase activity by a glucose phosphorylation assay following culture with HC plus alloxan (Alx). Treatment with HC resulted in concentration-dependent inhibition of insulin secretion induced by glucose and other insulinotropic agents. HC in combination with Alx resulted in a more pronounced decline in insulin secretion, including that induced by 20 mM alanine, by 43% (P<0.001) and 30 mM KCl by 60% (P<0.001), compared with control culture. The glucokinase phosphorylating capacity in cells cultured with HC plus Alx was significantly lower, compared with control cells. The cells also displayed a significant 84% (P<0.001) decline in cell viability. Prolonged, 72-h culture of insulin-secreting cells with HC followed by 18-h culture without HC did not result in full restoration of beta cell responses to insulinotropic agents. In vitro oxygen consumption was enhanced by a combination of Alx with HC. The study arrived at the conclusion that HC generates ROS in a redox-cycling reaction with Alx that explains the decline in viability of insulin-secreting cells, leading to reduced glucokinase phosphorylating ability, diminished insulin secretory responsiveness and cell death. Journal of Endocrinology (2012) 214, 233-238

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences > School of Biomedical Sciences
Faculty of Life and Health Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Diabetes
ID Code:23244
Deposited By: Dr Nigel Irwin
Deposited On:11 Sep 2012 09:35
Last Modified:11 Sep 2012 09:35

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