PMID- 37319295
OWN - NLM
STAT- MEDLINE
DCOM- 20230619
LR  - 20231121
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 18
IP  - 6
DP  - 2023
TI  - A holistic view of muscle metabolic reprogramming through personalized metabolic 
      modeling in newly diagnosed diabetic patients.
PG  - e0287325
LID - 10.1371/journal.pone.0287325 [doi]
LID - e0287325
AB  - Type 2 diabetes mellitus (T2DM) is a challenging and progressive metabolic 
      disease caused by insulin resistance. Skeletal muscle is the major 
      insulin-sensitive tissue that plays a pivotal role in blood sugar homeostasis. 
      Dysfunction of muscle metabolism is implicated in the disturbance of glucose 
      homeostasis, the development of insulin resistance, and T2DM. Understanding 
      metabolism reprogramming in newly diagnosed patients provides opportunities for 
      early diagnosis and treatment of T2DM as a challenging disease to manage. Here, 
      we applied a system biology approach to investigate metabolic dysregulations 
      associated with the early stage of T2DM. We first reconstructed a human 
      muscle-specific metabolic model. The model was applied for personalized metabolic 
      modeling and analyses in newly diagnosed patients. We found that several pathways 
      and metabolites, mainly implicating in amino acids and lipids metabolisms, were 
      dysregulated. Our results indicated the significance of perturbation of pathways 
      implicated in building membrane and extracellular matrix (ECM). Dysfunctional 
      metabolism in these pathways possibly interrupts the signaling process and 
      develops insulin resistance. We also applied a machine learning method to predict 
      potential metabolite markers of insulin resistance in skeletal muscle. 13 
      exchange metabolites were predicted as the potential markers. The efficiency of 
      these markers in discriminating insulin-resistant muscle was successfully 
      validated.
CI  - Copyright: (c) 2023 Khoshnejat et al. This is an open access article distributed 
      under the terms of the Creative Commons Attribution License, which permits 
      unrestricted use, distribution, and reproduction in any medium, provided the 
      original author and source are credited.
FAU - Khoshnejat, Maryam
AU  - Khoshnejat M
AD  - Laboratory of Complex Biological Systems and Bioinformatics (CBB), Department of 
      Bioinformatics, Institute of Biochemistry and Biophysics (IBB), University of 
      Tehran, Tehran, Iran.
AD  - The UNESCO Chair on Interdisciplinary Research in Diabetes, Institute of 
      Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran.
FAU - Banaei-Moghaddam, Ali Mohammad
AU  - Banaei-Moghaddam AM
AUID- ORCID: 0000-0003-1298-3748
AD  - The UNESCO Chair on Interdisciplinary Research in Diabetes, Institute of 
      Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran.
AD  - Laboratory of Genomics and Epigenomics (LGE), Department of Biochemistry, 
      Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, 
      Iran.
FAU - Moosavi-Movahedi, Ali Akbar
AU  - Moosavi-Movahedi AA
AD  - The UNESCO Chair on Interdisciplinary Research in Diabetes, Institute of 
      Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran.
AD  - Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
FAU - Kavousi, Kaveh
AU  - Kavousi K
AUID- ORCID: 0000-0002-1906-3912
AD  - Laboratory of Complex Biological Systems and Bioinformatics (CBB), Department of 
      Bioinformatics, Institute of Biochemistry and Biophysics (IBB), University of 
      Tehran, Tehran, Iran.
AD  - The UNESCO Chair on Interdisciplinary Research in Diabetes, Institute of 
      Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran.
LA  - eng
PT  - Journal Article
DEP - 20230615
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Insulin)
RN  - 0 (Blood Glucose)
SB  - IM
MH  - Humans
MH  - *Diabetes Mellitus, Type 2
MH  - *Insulin Resistance
MH  - Insulin/metabolism
MH  - Blood Glucose/metabolism
MH  - Muscle, Skeletal/metabolism
PMC - PMC10270629
COIS- The authors have declared that no competing interests exist.
EDAT- 2023/06/15 19:14
MHDA- 2023/06/19 13:08
PMCR- 2023/06/15
CRDT- 2023/06/15 14:29
PHST- 2023/02/06 00:00 [received]
PHST- 2023/06/02 00:00 [accepted]
PHST- 2023/06/19 13:08 [medline]
PHST- 2023/06/15 19:14 [pubmed]
PHST- 2023/06/15 14:29 [entrez]
PHST- 2023/06/15 00:00 [pmc-release]
AID - PONE-D-23-02801 [pii]
AID - 10.1371/journal.pone.0287325 [doi]
PST - epublish
SO  - PLoS One. 2023 Jun 15;18(6):e0287325. doi: 10.1371/journal.pone.0287325. 
      eCollection 2023.