Gut Microbiota−Tryptophan Metabolism−GLP-1 Axis Participates in β-Cell Regeneration Induced by Dapagliflozin

• DOI: 10.2337/db23-0553
• Publication Date: 2024-03-12T18:49:58Z
• Authors: Yafei Jiang; Jin Yang; Li Xia; Tianjiao Wei; Xiaona Cui; Dandan Wang; Zirun Jin; Xiafang Lin; Fei Li; Kun Yang; Shan Lang; Ye Liu; Jing Hang; Zhe Zhang; Tianpei Hong; Rui Wei
• Keywords: Dapagliflozin; Tryptophan Metabolism; Cell metabolism

Sodium–glucose cotransporter 2 inhibitors, efficacious antidiabetic agents that have cardiovascular and renal benefits, can promote pancreatic β-cell regeneration in type diabetic mice. However, the underlying mechanism remains unclear. In this study, we aimed to use multiomics identify mediators involved induced by dapagliflozin. We showed dapagliflozin lowered blood glucose level, upregulated plasma insulin increased islet area db/db Dapagliflozin reshaped gut microbiota modulated microbiotic plasmatic metabolites related tryptophan metabolism, especially l-tryptophan, Notably, l-tryptophan mRNA level of glucagon-like peptide 1 (GLP-1) production–related gene (Gcg Pcsk1) expression promoted GLP-1 secretion cultured mouse intestinal L cells, it supernatant primary human islets, which was eliminated GPR142 antagonist. Transplant fecal from dapagliflozin-treated mice, supplementation or treatment with GLP-1, C-peptide levels Addition exendin 9-39, a receptor (GLP-1R) antagonist, Glp1r knockout diminished these beneficial effects. summary, mice promotes upregulating production, is mediated via metabolism. Article Highlights