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

Guerra, S Del; Grupillo, Maria; Masini, Matilde; Lupi, R; Bugliani, Marco; Torri, S; Boggi, Ugo; Chiaro, Marco Del; Vistoli, Fabio; Mosca, Franco; Prato, Stefano Del; Marchetti, Piero

doi:10.1002/dmrr.680

Cited by 109 publications

(70 citation statements)

References 41 publications

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“…Third, transient hyperglycemia causes longlasting epigenetic changes (29), which may promote systemic inflammation. Additionally, glucose fluctuation has also been shown to cause loss of pancreatic b-cells due to increased apoptotic cell death (30). The loss of pancreatic b-cells may result in deterioration of glycemic control (31) and subsequent progression of vascular complications or poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

Impact of Visit-to-Visit Glycemic Variability on the Risks of Macrovascular and Microvascular Events and All-Cause Mortality in Type 2 Diabetes: The ADVANCE Trial

et al. 2014

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OBJECTIVEThere is no consensus on the importance of visit-to-visit glycemic variability in diabetes. Therefore, we assessed the effects of visit-to-visit variability (VVV) in HbA 1c and fasting glucose on major outcomes in the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation) trial. RESEARCH DESIGN AND METHODSADVANCE was a factorial randomized controlled trial of intensive glucose control and blood pressure lowering in patients with type 2 diabetes. VVV in the intensive glucose treatment group was defined using the SD of five measurements of HbA 1c and glucose taken 3-24 months after randomization. Outcomes were combined macro-and microvascular events and all-cause mortality occurring post 24 months. Sensitivity analyses were performed using other indices of variability and in the standard glucose treatment group. RESULTSAmong 4,399 patients in the intensive group, an increase in VVV of HbA 1c was associated with an increased risk of vascular events (P = 0.01) and with mortality (P < 0.001): highest versus lowest tenth hazard ratio (95% CI) 1.64 (1.05-2.55) and 3.31 (1.57-6.98), respectively, after multivariable adjustment. A clear association was also observed between VVV of fasting glucose and increased risk of vascular events (P < 0.001; 2.70 [1.65-4.42]). HbA 1c variability was positively associated with the risk of macrovascular events (P = 0.02 for trend), whereas glucose variability was associated with both macro-and microvascular events (P = 0.005 and P < 0.001 for trend, respectively). Sensitivity analyses using other indices, and patients in the standard glucose treatment group, were broadly consistent with these results. CONCLUSIONSConsistency of glycemic control is important to reduce the risks of vascular events and death in type 2 diabetes.

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Section: Discussionmentioning

confidence: 99%

Impact of Visit-to-Visit Glycemic Variability on the Risks of Macrovascular and Microvascular Events and All-Cause Mortality in Type 2 Diabetes: The ADVANCE Trial

et al. 2014

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“…T2DM is also characterized by the presence of oxidative stress (Davi et al 1999), and diabetic patients with NAFLD have higher levels of markers of oxidative stress compared to diabetic patients without NAFLD (Narasimhan et al 2010). Recently, several studies have demonstrated that IHG can generate more ROS than SHG in endothelial cells (Quagliaro et al 2003, Piconi et al 2006, islet cell (Del Guerra et al 2007, Kim et al 2012 and Schwann cells (Sun et al 2012a,b). We found that in the presence of lipotoxicity, SHG produced an increase in oxidative stress; moreover, the IHG appeared to further enhance oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Glucose fluctuation increased hepatocyte apoptosis under lipotoxicity and the involvement of mitochondrial permeability transition opening

Yin¹,

Zheng²,

Pan³

et al. 2015

Journal of Molecular Endocrinology

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Oxidative stress is considered to be an important factor in producing lethal hepatocyte injury associated with nonalcoholic fatty liver disease (NAFLD). Glucose fluctuation, more pronounced in patients with diabetes, has been recognized as an even stronger oxidative stress inducer than the sustained hyperglycemia. Here, we investigated the role of glucose variability in the development of the NAFLD based on hepatocyte apoptosis and possible mechanisms. To achieve this goal we studied C57BL/6J mice that were maintained on a high fat diet (HFD) and injected with glucose (3 g/kg) twice daily to induce intermittent high glucose (IHG). We also studied hepatic L02 cells incubated with palmitic acid (PA) to induce steatosis. The following experimental groups were compared: normal glucose (NG), sustained high glucose (SHG) and IHG with or without PA. We found that, although hepatic enzyme levels and liver lipid deposition were comparable between HFD mice injected with glucose or saline, the glucose injected mice displayed marked hepatocyte apoptosis and inflammation, accompanied by increased lipid peroxide in liver. In vitro, in the presence of PA, IHG increased L02 cell apoptosis and oxidative stress and produced pronounced mitochondrial dysfunction relative to the NG and SHG groups. Furthermore, treatment with the mitochondrial permeability transition (MPT) inhibitor, cyclosporin A (1.5 mmol/l), prevented mitochondrial dysfunction, oxidative stress and hepatocyte apoptosis. Our data suggests that IHG under lipotoxicity might contribute to the development of NAFLD by increasing oxidative stress and hepatocyte apoptosis via MPT and its related mitochondrial dysfunction.

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“…Several lines of evidence underscore a role for chronic hyperglycaemia-termed 'glucotoxicity'-in increased beta cell apoptosis. Thus, elevated glucose concentrations trigger apoptosis in cultured islets and beta cell lines [4][5][6][7][8] and in animal models of type 2 diabetes [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Inhibitor of differentiation proteins protect against oxidative stress by regulating the antioxidant–mitochondrial response in mouse beta cells

et al. 2015

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Aims/hypothesis Oxidative stress is implicated in beta cell glucotoxicity in type 2 diabetes. Inhibitor of differentiation (ID) proteins are transcriptional regulators induced by hyperglycaemia in islets, but the mechanisms involved and their role in beta cells are not clear. Here we investigated whether or not oxidative stress regulates ID levels in beta cells and the role of ID proteins in beta cells during oxidative stress. Methods MIN6 cells were cultured in H 2 O 2 or ribose to induce oxidative stress. ID1, ID3 and small MAF proteins (MAFF, MAFG and MAFK) were inhibited using small interfering RNA. Isolated islets from Id1

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

Abstract: 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.

Cited by 109 publications

References 41 publications

Impact of Visit-to-Visit Glycemic Variability on the Risks of Macrovascular and Microvascular Events and All-Cause Mortality in Type 2 Diabetes: The ADVANCE Trial

Impact of Visit-to-Visit Glycemic Variability on the Risks of Macrovascular and Microvascular Events and All-Cause Mortality in Type 2 Diabetes: The ADVANCE Trial

Glucose fluctuation increased hepatocyte apoptosis under lipotoxicity and the involvement of mitochondrial permeability transition opening

Inhibitor of differentiation proteins protect against oxidative stress by regulating the antioxidant–mitochondrial response in mouse beta cells

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