ArticleDiabetes2024
Gut Microbiota-Tryptophan Metabolism-GLP-1 Axis Participates in β-Cell Regeneration Induced by Dapagliflozin.
Article in Diabetes, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 29 citations in OpenAlex.
- Efficacy of Xiaokeqing granules and lifestyle intervention in treating prediabetes mellitus considering metabolomic biomarkers: A randomised controlled trial.World journal of diabetes · 2025Trial
- Glucagon-like peptide-1: a critical link between gut microbiota dysbiosis and degenerative musculoskeletal diseases.Gut microbes · 2026Review
- Gut microbiota metabolic reprogramming drives the development of metabolic diseases in the host.Gut microbes · 2026Review
- Design, synthesis and biological evaluation of quinazoline-carbazole derivatives as dual TXNIP/DYRK1A inhibitors for the treatment of type 2 diabetes mellitus.Molecular diversity · 2026Article
- Amino acid homeostasis in the kidney: Physiological roles and pathological dysregulation.Physiological reports · 2026Review
- Antihyperglycemic and Antioxidant Effects ofPharmaceutics · 2026Article
- Liraglutide and Dapagliflozin Synergistically Reshape Gut Microbiota and Metabolic Profiles to Ameliorate Type‑2 Diabetes in Mice.ACS omega · 2026Article
- GLP-1 and Parkinson's Disease: A Comprehensive Review of Biology, Mechanisms and Efficacy.Cells · 2026Review
- Gut microbiota and pancreatic cancer: tumorigenesis, progression, and clinical applications.Cancer biology & medicine · 2026Review
- Role and mechanisms of vascular smooth muscle cell phenotypic transition in diabetic macrovascular complications.Biological research · 2026Review
- Molecular mechanisms and structure-activity relationships of natural polysaccharides in ameliorating type 2 diabetes mellitus: a comprehensive review.Frontiers in nutrition · 2026Review
- Beyond conventional therapies: Gut microbiota modulation and macromolecular drugs in the battle against cardiometabolic diseases.Journal of pharmaceutical analysis · 2026Review
- Dapagliflozin improves diabetic kidney disease by inhibiting ferroptosis through β-hydroxybutyrate production.Renal failure · 2025Article
- Gut Microbiota-Derived Metabolites Orchestrate Metabolic Reprogramming in Diabetic Cardiomyopathy: Mechanisms and Therapeutic Frontiers.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Type 2 Diabetes and the Multifaceted Gut-X Axes.Nutrients · 2025Review
- Article
- Gut Microbiota and Metabolites: Biomarkers and Therapeutic Targets for Diabetes Mellitus and Its Complications.Nutrients · 2025Review
- GLP-1 receptor agonists show no detrimental effect on sperm quality in mouse models and cell lines.Endocrine · 2025Article
- GLP-1 and Its Role in Glycogen Production: A Narrative Review.Biomedicines · 2025Review
- Harnessing beta-cell replication: advancing molecular insights to regenerative therapies in diabetes.Frontiers in endocrinology · 2025Review
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
Sodium-glucose cotransporter 2 inhibitors, efficacious antidiabetic agents that have cardiovascular and renal benefits, can promote pancreatic β-cell regeneration in type 2 diabetic mice. However, the underlying mechanism remains unclear. In this study, we aimed to use multiomics to identify the mediators involved in β-cell regeneration induced by dapagliflozin. We showed that dapagliflozin lowered blood glucose level, upregulated plasma insulin level, and increased islet area in db/db mice. Dapagliflozin reshaped gut microbiota and modulated microbiotic and plasmatic metabolites related to tryptophan metabolism, especially l-tryptophan, in the diabetic mice. Notably, l-tryptophan upregulated the mRNA level of glucagon-like peptide 1 (GLP-1) production-related gene (Gcg and Pcsk1) expression and promoted GLP-1 secretion in cultured mouse intestinal L cells, and it increased the supernatant insulin level in primary human islets, which was eliminated by GPR142 antagonist. Transplant of fecal microbiota from dapagliflozin-treated mice, supplementation of l-tryptophan, or treatment with dapagliflozin upregulated l-tryptophan, GLP-1, and insulin or C-peptide levels and promoted β-cell regeneration in db/db mice. Addition of exendin 9-39, a GLP-1 receptor (GLP-1R) antagonist, or pancreatic Glp1r knockout diminished these beneficial effects. In summary, treatment with dapagliflozin in type 2 diabetic mice promotes β-cell regeneration by upregulating GLP-1 production, which is mediated via gut microbiota and tryptophan metabolism. ARTICLE HIGHLIGHTS:
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.