Exenatide ameliorates hydrogen peroxide-induced pancreatic β-cell apoptosis through regulation of METTL3-mediated m 6 A methylation

• Published in: European journal of pharmacology Vol. 924; p. 174960
• Main Authors: Zhou, Simin, Sun, Yue, Xing, Yujie, Wang, Zhi, Wan, Shujun, Yao, Xinming, Hua, Qiang, Meng, Xiangjian, Cheng, Jinhan, Zhong, Min, Lv, Kun, Kong, Xiang
• Format: Journal Article
• Language: English
• Published: Netherlands 05.06.2022
• Subjects: Animals; Apoptosis; Exenatide - pharmacology; Hydrogen Peroxide - toxicity; Methylation; Methyltransferases - genetics; Mice; RNA; N-methyladenosine; Hydrogen peroxide; METTL3; β-cell; Exenatide; Apoptosis
• ISSN: 1879-0712

Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is a commonly used hypoglycemic agent in clinical practice; it inhibits reactive oxygen species-induced pancreatic β-cell apoptosis. N -methyladenosine (m A) is produced by the methylation of RNA N6 residues and has recently been shown to play a crucial role in the regulation of islet β-cell growth and development. However, the involvement of m A methylation in the β-cell protective effects of exenatide has not been clarified. In this study, the m A-methylated RNA content and methyltransferase-like 3 (METTL3) expression levels in NIT-1 cells and primary mouse islets were found to significantly decrease following treatment with hydrogen peroxide (H O ). Treatment with exenatide induced an increase in m A content and METTL3 expression in the H O -treated NIT-1 cells and islets. Moreover, METTL3 silencing resulted in NIT-1 cell apoptosis under normal culture conditions. METTL3 upregulation significantly ameliorated H O -induced apoptosis in NIT-1 cells and primary islets. Furthermore, the anti-apoptotic effects of exenatide were obviously reversed by METTL3 knockdown. In conclusion, these findings suggest that exenatide elicits its anti-apoptotic effects in pancreatic β-cells by promoting m A methylation through the upregulation METTL3 expression.