Role of sirtuin-1 (SIRT1) in hypoxic injury in pancreatic β-cells. (2nd January 2021)

• Record Type: Journal Article
• Authors: Lee, Ye-Jee; Lee, Esder; You, Young-Hye; Ahn, Yu-Bae; Song, Ki-Ho; Kim, Ji-Won; Ko, Seung-Hyun
• Is Part Of: Journal of drug targeting. Volume 29:Number 1(2021)
• Page Start: 88
• Page End: 98
• Publication Date: 2021-01-02
• Subjects: Diabetes -- hypoxia -- pancreatic β-cell -- sirtuin-1(SIRT1) -- apoptosis -- cytokine -- SIRT1 activation; Drug delivery systems -- Periodicals; Drug Delivery Systems; Vehicles; Drug Administration Routes; Drug Evaluation; 615.7
• DOI: 10.1080/1061186X.2020.1806285
• Languages: English
• ISSNs: 1061-186X

Abstract

Abstract: Islet transplantation (ITx) is being developed as a treatment for type 1 diabetes mellitus, but hypoxic damage to transplanted islet grafts is an important factor affecting successful transplantation. To investigate the role of sirtuin-1 (SIRT1) under hypoxic injury in INS-1 cells, one type of pancreatic β-cell lines, we used SRT1720 and GW4064 for SIRT1 activation. The small interfering RNA SIRT1 (si-SIRT1) was used to suppress SIRT1 gene expression. We measured cell viability, apoptosis, and the levels of inflammatory cytokines, including tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and reactive oxygen species (ROS), under hypoxic conditions. Real-time PCR and Western blot analysis were performed. Cell viability was significantly reduced to 71% and 40% after 4 and 6 h of hypoxic conditions, respectively. Apoptosis increased significantly 2.8-fold and 5.3-fold after 4 and 6 h of hypoxia, respectively. SIRT1 expression was significantly reduced at the mRNA and protein levels during hypoxia. Hypoxic damage significantly increased the TNF-α, IL-6 and ROS levels in INS-1 cells. However, the reduced cell viability and increased inflammatory cytokines from hypoxic damage were ameliorated by SIRT1 activation in INS-1 cells. These results suggest that SIRT1 is a potential target for the protection of pancreatic β-cells against hypoxic damage during ITx.