PMID- 33664666
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210306
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 11
DP  - 2020
TI  - Obesity Connected Metabolic Changes in Type 2 Diabetic Patients Treated With 
      Metformin.
PG  - 616157
LID - 10.3389/fphar.2020.616157 [doi]
LID - 616157
AB  - Metformin is widely used in the treatment of Type 2 Diabetes Mellitus (T2DM). 
      However, it is known to have beneficial effects in many other conditions, 
      including obesity and cancer. In this study, we aimed to investigate the 
      metabolic effect of metformin in T2DM and its impact on obesity. A mass 
      spectrometry (MS)-based metabolomics approach was used to analyze samples from 
      two cohorts, including healthy lean and obese control, and lean as well as obese 
      T2DM patients on metformin regimen in the last 6 months. The results show a clear 
      group separation and sample clustering between the study groups due to both T2DM 
      and metformin administration. Seventy-one metabolites were dysregulated in 
      diabetic obese patients (30 up-regulated and 41 down-regulated), and their levels 
      were unchanged with metformin administration. However, 30 metabolites were 
      dysregulated (21 were up-regulated and 9 were down-regulated) and then restored 
      to obese control levels by metformin administration in obese diabetic patients. 
      Furthermore, in obese diabetic patients, the level of 10 metabolites was 
      dysregulated only after metformin administration. Most of these dysregulated 
      metabolites were dipeptides, aliphatic amino acids, nucleic acid derivatives, and 
      urea cycle components. The metabolic pattern of 62 metabolites was persistent, 
      and their levels were affected by neither T2DM nor metformin in obesity. 
      Interestingly, 9 metabolites were significantly dysregulated between lean and 
      obese cohorts due to T2DM and metformin regardless of the obesity status. These 
      include arginine, citrulline, guanidoacetic acid, proline, alanine, taurine, 
      5-hydroxyindoleacetic acid, and 5-hydroxymethyluracil. Understanding the 
      metabolic alterations taking place upon metformin treatment would shed light on 
      possible molecular targets of metformin, especially in conditions like T2DM and 
      obesity.
CI  - Copyright (c) 2021 Aleidi, Dahabiyeh, Gu, Al Dubayee, Alshahrani, Benabdelkamel, 
      Mujammami, Li, Aljada and Abdel Rahman.
FAU - Aleidi, Shereen M
AU  - Aleidi SM
AD  - Department of Biopharmaceutics and Clinical Pharmacy, School of Pharmacy, The 
      University of Jordan, Amman, Jordan.
FAU - Dahabiyeh, Lina A
AU  - Dahabiyeh LA
AD  - Department of Pharmaceutical Sciences, School of Pharmacy, The University of 
      Jordan, Amman, Jordan.
FAU - Gu, Xinyun
AU  - Gu X
AD  - Department of Chemistry, University of Alberta, Edmonton, AB, Canada.
FAU - Al Dubayee, Mohammed
AU  - Al Dubayee M
AD  - College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, 
      Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.
FAU - Alshahrani, Awad
AU  - Alshahrani A
AD  - College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, 
      Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.
FAU - Benabdelkamel, Hicham
AU  - Benabdelkamel H
AD  - Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud 
      University, Riyadh, Saudi Arabia.
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 - Li, Liang
AU  - Li L
AD  - Department of Chemistry, University of Alberta, Edmonton, AB, Canada.
FAU - Aljada, Ahmad
AU  - Aljada A
AD  - Department of Biochemistry and Molecular Medicine, College of Medicine, Al Faisal 
      University, Riyadh, Saudi Arabia.
FAU - Abdel Rahman, Anas M
AU  - Abdel Rahman AM
AD  - Department of Biochemistry and Molecular Medicine, College of Medicine, Al Faisal 
      University, Riyadh, Saudi Arabia.
AD  - Metabolomics Section, Department of Clinical Genomics, Center for Genomics 
      Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi 
      Arabia.
AD  - Department of Chemistry, Memorial University of Newfoundland, St. John's, NL, 
      Canada.
LA  - eng
PT  - Journal Article
DEP - 20210216
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC7921791
OTO - NOTNLM
OT  - amino acid, T2DM
OT  - body mass index-BMI
OT  - mass spectrometry-LC-MS/MS
OT  - metabolomics
OT  - metformin
OT  - obesity
OT  - type 2 diabete 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- 2021/03/06 06:00
MHDA- 2021/03/06 06:01
PMCR- 2021/02/16
CRDT- 2021/03/05 06:05
PHST- 2020/10/11 00:00 [received]
PHST- 2020/12/30 00:00 [accepted]
PHST- 2021/03/05 06:05 [entrez]
PHST- 2021/03/06 06:00 [pubmed]
PHST- 2021/03/06 06:01 [medline]
PHST- 2021/02/16 00:00 [pmc-release]
AID - 616157 [pii]
AID - 10.3389/fphar.2020.616157 [doi]
PST - epublish
SO  - Front Pharmacol. 2021 Feb 16;11:616157. doi: 10.3389/fphar.2020.616157. 
      eCollection 2020.