Volume 23, Issue 3 pp. 234-238
Research Article

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

S Del Guerra

S Del Guerra

Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy

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M Grupillo

M Grupillo

Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy

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M Masini

M Masini

Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy

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R Lupi

R Lupi

Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy

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M Bugliani

M Bugliani

Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy

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S Torri

S Torri

Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy

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U Boggi

U Boggi

Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy

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M Del Chiaro

M Del Chiaro

Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy

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F Vistoli

F Vistoli

Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy

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F Mosca

F Mosca

Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy

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S Del Prato

S Del Prato

Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy

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P Marchetti

Corresponding Author

P Marchetti

Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy

Department of Endocrinology and Metabolism, Metabolic Unit, Ospedale Cisanello, via Paradisa 2, 56100 Pisa—Italy.Search for more papers by this author
First published: 23 February 2007
Citations: 100

Abstract

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.

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