Journal
TOXICOLOGY IN VITRO
Volume 65, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2020.104808
Keywords
Resveratrol; SIRT1-UCP2 axis; Ethanol; beta-Cell dysfunction
Categories
Funding
- National key research and development program of China [2018YFC1603100]
- National Natural Science Foundation of China [81172657]
Ask authors/readers for more resources
SIRT1 has been proposed to enhance insulin secretion in beta-cell through repressing the expression of uncoupling protein2 (UCP2), but whether ethanol-induced beta-cell dysfunction is mediated by the disrupted SIRT1-UCP2 axis remains unknown. This study was conducted to explore the underlying mechanisms by which ethanol resulted in beta-cell dysfunction and the potential protective effects of resveratrol in this process. INS-1 cells (rat pancreatic beta-cell line) were cultured with ethanol in the presence or absence of resveratrol (2.5, 12.5 mu mol/L). The results showed that ethanol exposure reduced glucose-stimulated insulin secretion, ATP production and SIRT1 expression but increased UCP2 expression, while supplementation with resveratrol restored the function of INS-1 cell by upregulating SIRT1 and inhibiting UCP2. Moreover, the critical role of SIRT1-UCP2 axis was further supported by the results that SIRT1 activator SRT1720 reversed ethanol-induced impairment of glucose-stimulated insulin secretion by decreasing UCP2, while SIRT1 inhibitor Ex527 abolished the beneficial effects of resveratrol. Meanwhile, NAD(+) booster nicotinamide mononucleotide also counteracted the deleterious effects of ethanol by increasing SIRT1, suggesting the regulation of SIRT1-UCP2 axis may be associated with cellular NAD(+)/NADH ratio. In conclusion, our observations imply that ethanol induces impaired insulin secretion from INS-1 cell through disrupting SIRT1-UCP2 axis, while resveratrol may reverse this process by augmenting SIRT1 and inhibiting UCP2.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available