Year: 2020
Type: article
Abstract: Islet transplantation is an attractive treatment for type 1 diabetic patients. However, transplanted islets suffered from considerable cell death due to inflammatory reactions and oxidative stress. Ferroptosis is a programmed death characterized by iron-dependent lipid peroxidation, which has been implicated in the islet loss and dysfunction. Our previous studies showed that bilirubin displayed protection effect for islets by inhibiting early inflammation and oxidative stress. However, whether bilirubin protects islets by targeting ferroptosis has not yet been elucidated. Here, the isolated islet was exposed to ferroptosis-inducing agents with or without bilirubin. Islet viability, insulin secretion, and oxidative stress levels were assessed. Subsequently, the pretreated islets were transplanted into the subrenal site of streptozotocin-induced diabetic mice. Bilirubin could significantly attenuate ferroptosis in isolated islets, along with reduced oxidative stress, elevated GPX4 expression and upregulation of Nrf2/HO-1. Experimental data also confirmed that bilirubin could chelate iron. In vivo graft study demonstrated that euglycemia was achieved in diabetic mice receiving bilirubin-pretreated islets within 24 hours, while the control islets required at least 7 days. Bilirubin could improve islet viability and function through inhibiting ferroptosis, which could be of clinic interest to apply bilirubin into the islet transplantation system.
Source: Frontiers in Pharmacology
Authors: Qing Yao, Rui Sun, Shihui Bao, Ruijie Chen, Longfa Kou
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,950
Funders: National Natural Science Foundation of China, Wenzhou Municipal Science and Technology Bureau, Primary Research and Development Plan of Zhejiang Province, National Major Science and Technology Projects of China, Natural Science Foundation of Zhejiang Province, Key Research and Development Program of Zhejiang Province
OpenAlex ID: W3036733618