| Quercetin potentiates insulin secretion and protects INS-1 pancreatic β-cells against oxidative damage via the ERK1/2 pathway. | |
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MedLine Citation:
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PMID: 20860660 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND AND PURPOSE: Quercetin lowers plasma glucose, normalizes glucose tolerance tests and preserves pancreatic β-cell integrity in diabetic rats. However, its mechanism of action has never been explored in insulin-secreting β-cells. Using the INS-1 β-cell line, the effects of quercetin were determined on glucose- or glibenclamide-induced insulin secretion and on β-cell dysfunctions induced by hydrogen peroxide (H(2)O(2)). 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 µmol·L(-1)) potentiated both glucose (8.3 mmol·L(-1))- and glibenclamide (0.01 µmol·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 µmol·L(-1)), protected β-cell function and viability against oxidative damage induced by 50 µmol·L(-1) H(2)O(2) 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 β-cells against oxidative damage. Our study suggested that ERK1/2 played a major role in those effects. The potential of quercetin in preventing β-cell dysfunction associated with diabetes deserves further investigation. |
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Authors:
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E Youl; G Bardy; R Magous; G Cros; F Sejalon; A Virsolvy; S Richard; J F Quignard; R Gross; P Petit; D Bataille; C Oiry |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: British journal of pharmacology Volume: 161 ISSN: 1476-5381 ISO Abbreviation: Br. J. Pharmacol. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-23 Completed Date: 2010-12-02 Revised Date: 2012-05-07 |
Medline Journal Info:
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Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 799-814 Citation Subset: IM |
Copyright Information:
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© 2010 The Authors. British Journal of Pharmacology © 2010 The British Pharmacological Society. |
Affiliation:
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Université Montpellier I et CNRS UMR 5232, Centre de Pharmacologie et Innovation dans le Diabète (CPID), Montpellier, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcysteine
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pharmacology Animals Antioxidants / pharmacology* Cell Line Glucose / metabolism Glyburide / pharmacology Hydrogen Peroxide / toxicity Hypoglycemic Agents / pharmacology Insulin / secretion* Insulin-Secreting Cells / drug effects*, metabolism Male Mitogen-Activated Protein Kinase 1 / metabolism Mitogen-Activated Protein Kinase 3 / metabolism Oxidative Stress / drug effects Phosphorylation / drug effects Quercetin / pharmacology* Rats Rats, Wistar Signal Transduction / drug effects Stilbenes / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Antioxidants; 0/Hypoglycemic Agents; 0/Insulin; 0/Stilbenes; 10238-21-8/Glyburide; 117-39-5/Quercetin; 50-99-7/Glucose; 501-36-0/resveratrol; 616-91-1/Acetylcysteine; 7722-84-1/Hydrogen Peroxide; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3 |
| Comments/Corrections | |
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