Potential metabolic pathways and targets of dapagliflozin in treatment of type 2 diabetes mellitus: based on integrative omics
10.3760/cma.j.cn311282-20250826-00422
- VernacularTitle:基于整合组学探究达格列净治疗2型糖尿病的潜在代谢途径及作用靶点
- Author:
Yang SHI
1
;
Yujing ZHU
;
Meng LI
;
Weiting XIANG
;
Aixia XIE
;
Nong LI
;
Shengli WU
Author Information
1. 克拉玛依市中西医结合医院（克拉玛依市人民医院）药剂科，克拉玛依 834000
- Publication Type:Journal Article
- Keywords:
Dapagliflozin;
Diabetes mellitus, type 2;
Metabolomics;
Proteomics;
Signaling pathway;
Metabolic pathway
- From:
Chinese Journal of Endocrinology and Metabolism
2025;41(11):930-939
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the metabolic pathways and potential molecular targets associated with dapagliflozin in the treatment of type 2 diabetes mellitus.Methods:Plasma samples from patients with type 2 diabetes mellitus were collected before and after 12 months of dapagliflozin treatment and analyzed using UPLC-VION IMS Q-Tof-based metabolomics and timsTOF Pro2 diaPASEF-based proteomics. Multivariate statistical analyses were performed to identify significant differences pre- and post-treatment. Correlation analysis was then conducted to assess relationships between differentially expressed metabolites and proteins closely associated with type 2 diabetes mellitus. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were used to construct metabolic pathway maps and predict therapeutic targets.Results:After 12 months of dapagliflozin treatment, 162 differential metabolites were identified, with 59 upregulated and 103 downregulated. A total of 440 differentially expressed proteins were detected, of which 272 were upregulated and 168 were downregulated. The main classes of differential metabolites included sphingolipids, glycerophospholipids, and glycosphingolipids. Key differentially expressed proteins included importin subunit alpha-11, synemin, Janus kinase 1, and far upstream element-binding protein 2. Correlation analysis revealed 98 shared enriched pathways between differential metabolites and proteins, involving neurotrophin signaling, chemokine signaling, and B cell receptor signaling pathways. Metabolic pathway analysis suggested that dapagliflozin might regulate insulin secretion by modulating glucose-dependent insulinotropic polypeptide, calmodulin-dependent protein kinase, and diacylglycerol levels.Conclusion:Dapagliflozin may exert therapeutic effects in type 2 diabetes mellitus through multiple mechanisms, including the modulation of metabolic and proteomic profiles, participation in key cellular signaling pathways, and regulation of insulin secretion.
