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A Metabolic Pattern in Healthy Subjects Given a Single Dose of Metformin: A Metabolomics Approach
- Source :
- Frontiers in Pharmacology, Frontiers in Pharmacology, Vol 12 (2021)
- Publication Year :
- 2021
- Publisher :
- Frontiers Media SA, 2021.
-
Abstract
- Metformin is a widely prescribed medication for the treatment of type 2 diabetes mellitus (T2DM). It possesses effective roles in various disorders, including cancer, dyslipidemia, and obesity. However, the underlying mechanisms of metformin's multiple benefits are not fully understood. Herein, a mass spectrometry-based untargeted metabolomics approach was used to investigate the metabolic changes associated with the administration of a single dose of metformin in the plasma of 26 healthy subjects at five-time points; pre-dose, before the maximum concentration of metformin (Cmax), Cmax, after Cmax, and 36 h post-dose. A total of 111 metabolites involved in various biochemical processes were perturbed, with branched-chain amino acid (BCAA) being the most significantly altered pathway. Additionally, the Pearson similarity test revealed that 63 metabolites showed a change in their levels dependent on metformin level. Out of these 63, the level of 36 metabolites was significantly altered by metformin. Significantly altered metformin-dependent metabolites, including hydroxymethyl uracil, propionic acid, glycerophospholipids, and eicosanoids, pointed to fundamental biochemical processes such as lipid network signaling, energy homeostasis, DNA lesion repair mechanisms, and gut microbiota functions that could be linked to the multiple beneficial roles of metformin. Thus, the distinctive metabolic pattern linked to metformin administration can be used as a metabolic signature to predict the potential effect and mechanism of actions of new chemical entities during drug development.
- Subjects :
- 0301 basic medicine
glycerophospholipid
endocrine system diseases
type 2 diabetes mellitus
Cmax
030209 endocrinology & metabolism
RM1-950
Pharmacology
Gut flora
eicosanoids
Energy homeostasis
03 medical and health sciences
0302 clinical medicine
Metabolomics
cancer
Medicine
Pharmacology (medical)
branched-chain amino acids
Original Research
mass spectrometry
biology
business.industry
digestive, oral, and skin physiology
nutritional and metabolic diseases
Type 2 Diabetes Mellitus
medicine.disease
biology.organism_classification
metabolomics
Metformin
030104 developmental biology
Drug development
Therapeutics. Pharmacology
metformin
business
Dyslipidemia
medicine.drug
Subjects
Details
- ISSN :
- 16639812
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Frontiers in Pharmacology
- Accession number :
- edsair.doi.dedup.....4a789d901397fc157c02c2e341af38ca