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Gliclazide protects human islet beta-cells from apoptosis induced by intermittent high glucose

Background Decreased beta‐cell mass, mainly due to apoptosis, is crucial for the development and progression of type 2 diabetes. Chronic exposure to high glucose levels is a probable underlying mechanism, whereas the role of oral anti‐diabetic agents (sulphonylureas in particular) is still unsettled...

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Published in:Diabetes/metabolism research and reviews 2007-03, Vol.23 (3), p.234-238
Main Authors: Del Guerra, S, Grupillo, M, Masini, M, Lupi, R, Bugliani, M, Torri, S, Boggi, U, Del Chiaro, M, Vistoli, F, Mosca, F, Del Prato, S, Marchetti, P
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Language:English
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Summary:Background Decreased beta‐cell mass, mainly due to apoptosis, is crucial for the development and progression of type 2 diabetes. Chronic exposure to high glucose levels is a probable underlying mechanism, whereas the role of oral anti‐diabetic agents (sulphonylureas in particular) is still unsettled. Methods To directly investigate more on such issues, we prepared isolated human islets, which were then cultured for 5 days in continuous normal glucose concentration (NG, 5.5 mmol/L) or normal and high (HG, 16.7 mmol/L) glucose levels (alternating every 24 h), with or without the addition of therapeutical concentration (10 µmolL) of gliclazide or glibenclamide. Results Intermittent high glucose caused a significant decrease of glucose‐stimulated insulin secretion, which was not further affected by either sulphonylurea. Apoptosis, as assessed by electron microscopy, was also significantly increased by alternating high glucose exposure, which was accompanied by altered mitochondria morphology and density volume, and increased concentrations of nitrotyrosine, a marker of oxidative stress. Gliclazide, but not glibenclamide, was able to significantly reduce high glucose induced apoptosis, mitochondrial alterations, and nitrotyrosine concentration increase. Conclusion Therefore, gliclazide protected human beta‐cells from apoptosis induced by intermittent high glucose, and this effect was likely to be due, at least in part, to the anti‐oxidant properties of the molecule. Copyright © 2006 John Wiley & Sons, Ltd.
ISSN:1520-7552
1520-7560
DOI:10.1002/dmrr.680