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Resveratrol prevents interleukin-1β-induced dysfunction of pancreatic β-cells
Fang Chen1, Xiaohua Zhou, Yan Lin
1Key Laboratory of Human Functional Genomics of Jiangsu Province, Clinical Diabetes Centre of Jiangsu Province, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
Objective:
Interleukin-1β (IL-1β) plays an important role in the development of type 1 and type 2 diabetes mellitus. Resveratrol, a polyphenol, is known to have a wide range of pharmacological properties in vitro. In this research, we examined the effects of resveratrol on IL-1β-induced β-cell dysfunction.
Methods:
We first evaluated the effect of resveratrol on nitric oxide (NO) formation in RINm5F cells stimulated with IL-1β using the Griess method. Next, we performed transient transfection and reporter assays to measure the transcriptional activity of peroxisome proliferator-activated receptor-γ (PPAR-γ). We also used Western blotting analysis to assess the effect of resveratrol on inducible nitric oxide synthase (iNOS) expression and nuclear factor-κB (NF-κB) translocation to the nuclei in cells treated with IL-1β. In addition, we assessed the transcriptional activity of NF-κB using an electrophoretic mobility shift assay (EMSA). Finally, we evaluated the effect of resveratrol on IL-1β-induced inhibition of glucose-stimulated insulin secretion in freshly isolated rat pancreatic islets.
Results:
Resveratrol significantly suppressed IL-1β-induced NO production, a finding that correlated well with reduced levels of iNOS mRNA and protein. The molecular mechanism by which resveratrol inhibited iNOS gene expression appeared to involve increased PPAR-γ activity, which resulted in the inhibition of NF-κB activation. Further analysis showed that resveratrol could prevent IL-1β-induced inhibition of glucose-stimulated insulin secretion in rat islets.
Conclusion:
In this study, we demonstrated that resveratrol could protect against pancreatic β-cell dysfunction caused by IL-1β.
Insights
Resveratrol protects pancreatic beta cells from Interleukin-1β (IL-1β) induced dysfunction. This polyphenol reduces nitric oxide production and preserves insulin secretion, offering a potential therapeutic strategy for diabetes.
Area of Science:
- Endocrinology
- Molecular Biology
- Pharmacology
Background:
- Interleukin-1β (IL-1β) is implicated in the pathogenesis of type 1 and type 2 diabetes mellitus.
- Resveratrol, a naturally occurring polyphenol, exhibits diverse pharmacological activities.
- IL-1β contributes to pancreatic beta-cell dysfunction, a key factor in diabetes development.
Purpose of the Study:
- To investigate the protective effects of resveratrol against IL-1β-induced pancreatic beta-cell dysfunction.
- To elucidate the molecular mechanisms underlying resveratrol's action on beta cells exposed to IL-1β.
Main Methods:
- Assessed nitric oxide (NO) production using the Griess assay.
- Measured peroxisome proliferator-activated receptor-γ (PPAR-γ) transcriptional activity via reporter assays.
- Evaluated inducible nitric oxide synthase (iNOS) expression and nuclear factor-κB (NF-κB) activation using Western blotting and electrophoretic mobility shift assays (EMSA).
- Determined the impact on glucose-stimulated insulin secretion in isolated rat pancreatic islets.
Main Results:
- Resveratrol significantly reduced IL-1β-induced NO production, correlating with decreased iNOS mRNA and protein levels.
- The protective effect involved enhanced PPAR-γ activity, leading to the inhibition of NF-κB activation.
- Resveratrol prevented IL-1β-mediated impairment of glucose-stimulated insulin secretion in rat islets.
Conclusions:
- Resveratrol demonstrates a protective role against IL-1β-induced pancreatic beta-cell dysfunction.
- The findings suggest resveratrol's potential as a therapeutic agent for managing diabetes-related beta-cell damage.
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