Quercetin potentiates insulin secretion and protects INS-1 pancreatic β-cells against oxidative damage via the ERK1/2 pathway

被引:200
作者
Youl, E. [2 ]
Bardy, G. [2 ]
Magous, R. [2 ]
Cros, G. [2 ]
Sejalon, F. [2 ]
Virsolvy, A. [3 ]
Richard, S. [3 ]
Quignard, J. F. [4 ]
Gross, R. [2 ]
Petit, P. [2 ]
Bataille, D. [2 ]
Oiry, C. [1 ,2 ]
机构
[1] Fac Pharm Montpellier, CPID, CNRS, UMR 5232, F-34093 Montpellier 5, France
[2] Univ Montpellier I, Montpellier, France
[3] INSERM, CHU A de Villeneuve, U637, Montpellier, France
[4] Univ Bordeaux 2, INSERM, U885, F-33076 Bordeaux, France
关键词
quercetin; pancreatic beta-cells; insulin secretion; cell viability; ERK1/2; oxidative stress; diabetes; N-TERMINAL KINASE; ELEMENT-BINDING PROTEIN; INDUCED DIABETIC-RATS; HYDROGEN-PEROXIDE; SIGNALING PATHWAYS; RETICULUM CA2+-ATPASE; GLUCOSE TOXICITY; ACTIVATION; ISLETS; STRESS;
D O I
10.1111/j.1476-5381.2010.00910.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
BACKGROUND AND PURPOSE Quercetin lowers plasma glucose, normalizes glucose tolerance tests and preserves pancreatic beta-cell integrity in diabetic rats. However, its mechanism of action has never been explored in insulin-secreting beta-cells. Using the INS-1 beta-cell line, the effects of quercetin were determined on glucose- or glibenclamide-induced insulin secretion and on beta-cell dysfunctions induced by hydrogen peroxide (H2O2). These effects were analysed along with the activation of the extracellular signal-regulated kinase (ERK)1/2 pathway. N-acetyl-L-cysteine (NAC) and resveratrol, two antioxidants also known to exhibit some anti-diabetic properties, were used for comparison. EXPERIMENTAL APPROACH Insulin release was quantified by the homogeneous time resolved fluorescence method and ERK1/2 activation tested by Western blot experiments. Cell viability was estimated by the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MTT) colorimetric assay. KEY RESULTS Quercetin (20 mu mol.L-1) potentiated both glucose (8.3 mmol.L-1)- and glibenclamide (0.01 mu mol.L-1)- induced insulin secretion and ERK1/2 phosphorylation. The ERK1/2 (but not the protein kinase A) signalling pathway played a crucial role in the potentiation of glucose- induced insulin secretion by quercetin. In addition, quercetin (20 mu mol.L-1), protected b-cell function and viability against oxidative damage induced by 50 mu mol.L-1 H2O2 and induced a major phosphorylation of ERK1/2. In the same conditions, resveratrol or NAC were ineffective. CONCLUSION AND IMPLICATIONS Quercetin potentiated glucose and glibenclamide-induced insulin secretion and protected beta-cells against oxidative damage. Our study suggested that ERK1/2 played a major role in those effects. The potential of quercetin in preventing beta-cell dysfunction associated with diabetes deserves further investigation.
引用
收藏
页码:799 / 814
页数:16
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