Gliclazide protects human islet beta-cells from apoptosis induced by intermittent high glucose
S Del Guerra
Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy
Search for more papers by this authorM Grupillo
Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy
Search for more papers by this authorM Masini
Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy
Search for more papers by this authorR Lupi
Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy
Search for more papers by this authorM Bugliani
Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy
Search for more papers by this authorS Torri
Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy
Search for more papers by this authorU Boggi
Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy
Search for more papers by this authorM Del Chiaro
Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy
Search for more papers by this authorF Vistoli
Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy
Search for more papers by this authorF Mosca
Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy
Search for more papers by this authorS Del Prato
Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy
Search for more papers by this authorCorresponding 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 authorS Del Guerra
Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy
Search for more papers by this authorM Grupillo
Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy
Search for more papers by this authorM Masini
Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy
Search for more papers by this authorR Lupi
Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy
Search for more papers by this authorM Bugliani
Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy
Search for more papers by this authorS Torri
Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy
Search for more papers by this authorU Boggi
Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy
Search for more papers by this authorM Del Chiaro
Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy
Search for more papers by this authorF Vistoli
Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy
Search for more papers by this authorF Mosca
Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy
Search for more papers by this authorS Del Prato
Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa—Italy
Search for more papers by this authorCorresponding 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 authorAbstract
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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