PMID- 34335266
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210803
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 12
DP  - 2021
TI  - A Metabolic Pattern in Healthy Subjects Given a Single Dose of Metformin: A 
      Metabolomics Approach.
PG  - 705932
LID - 10.3389/fphar.2021.705932 [doi]
LID - 705932
AB  - 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 (C(max)), C(max), after C(max), 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.
CI  - Copyright (c) 2021 Dahabiyeh, Mujammami, Arafat, Benabdelkamel, Alfadda and Abdel 
      Rahman.
FAU - Dahabiyeh, Lina A
AU  - Dahabiyeh LA
AD  - Department of Pharmaceutical Sciences, School of Pharmacy, The University of 
      Jordan, Amman, Jordan.
FAU - Mujammami, Muhammad
AU  - Mujammami M
AD  - Endocrinology and Diabetes Unit, Department of Medicine, College of Medicine, 
      King Saud University, Riyadh, Saudi Arabia.
AD  - University Diabetes Center, King Saud University Medical City, King Saud 
      University, Riyadh, Saudi Arabia.
FAU - Arafat, Tawfiq
AU  - Arafat T
AD  - Jordan Center for Pharmaceutical Research, Amman, Jordan.
FAU - Benabdelkamel, Hicham
AU  - Benabdelkamel H
AD  - Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud 
      University, Riyadh, Saudi Arabia.
FAU - Alfadda, Assim A
AU  - Alfadda AA
AD  - Endocrinology and Diabetes Unit, Department of Medicine, College of Medicine, 
      King Saud University, Riyadh, Saudi Arabia.
AD  - Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud 
      University, Riyadh, Saudi Arabia.
FAU - Abdel Rahman, Anas M
AU  - Abdel Rahman AM
AD  - Metabolomics Section, Department of Clinical Genomics, Center for Genome 
      Medicine, King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh, 
      Saudi Arabia.
AD  - Department of Biochemistry and Molecular Medicine, College of Medicine, Al Faisal 
      University, Riyadh, Saudi Arabia.
AD  - Department of Chemistry, Memorial University of Newfoundland, St. John's, NL, 
      Canada.
LA  - eng
PT  - Journal Article
DEP - 20210715
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC8319764
OTO - NOTNLM
OT  - branched-chain amino acids
OT  - cancer
OT  - eicosanoids
OT  - glycerophospholipid
OT  - mass spectrometry
OT  - metabolomics
OT  - metformin
OT  - type 2 diabetes mellitus
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/08/03 06:00
MHDA- 2021/08/03 06:01
PMCR- 2021/07/15
CRDT- 2021/08/02 05:54
PHST- 2021/05/07 00:00 [received]
PHST- 2021/06/28 00:00 [accepted]
PHST- 2021/08/02 05:54 [entrez]
PHST- 2021/08/03 06:00 [pubmed]
PHST- 2021/08/03 06:01 [medline]
PHST- 2021/07/15 00:00 [pmc-release]
AID - 705932 [pii]
AID - 10.3389/fphar.2021.705932 [doi]
PST - epublish
SO  - Front Pharmacol. 2021 Jul 15;12:705932. doi: 10.3389/fphar.2021.705932. 
      eCollection 2021.