Significant reduction of apoptosis induced via hypoxia and oxidative stress in isolated human islet by resveratrol

Nutr Metab Cardiovasc Dis. 2020 Jun 25;30(7):1216-1226. doi: 10.1016/j.numecd.2020.04.011. Epub 2020 Apr 20.

Abstract

Background and aims: Successful islet transplantation as a promising treatment of diabetes type 1 is threatened with the loss of islets during the pre-transplant culture due to hypoxia and oxidative stress-induced apoptosis. Therefore, optimization of culture in order to preserve the islets is a critical point. In this study, we investigated the effect of resveratrol, as a cytoprotective agent, on the cultured human islets.

Methods and results: Isolated islets were treated with different concentrations of resveratrol for 24 and 72 h. Islets' viability, apoptosis, apoptosis markers, and insulin and C-peptide secretion, along with the production of reactive oxygen species (ROS), hypoxia inducible factor 1 alpha (HIF-1α), and its target genes in the islets were investigated. Our findings showed that the islets were exposed to hypoxia and oxidative stress after isolation and during culture. This insult induced apoptosis and decreased viability during 72 h. The presence of resveratrol significantly attenuated HIF-1α and ROS production, reduced apoptosis, promoted the VEGF secretion, and increased the insulin and C-peptide secretion. In this regard, resveratrol improved the islet's survival and function in the culture period.

Conclusions: Using resveratrol can attenuate the stressful condition for the islets in the pre-transplant culture and subsequently ameliorate their viability and functionality that lead to successful outcome after clinical transplantation.

Keywords: Apoptosis; Function; Human islet; Hypoxia; Oxidative stress; Resveratrol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects*
  • C-Peptide / metabolism
  • Cell Hypoxia
  • Cell Survival / drug effects
  • Cytoprotection
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / pathology
  • Middle Aged
  • Oxidative Stress / drug effects*
  • Reactive Oxygen Species / metabolism
  • Resveratrol / pharmacology*
  • Signal Transduction
  • Tissue Culture Techniques
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Antioxidants
  • C-Peptide
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Reactive Oxygen Species
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Resveratrol