PMID- 31225649
OWN - NLM
STAT- MEDLINE
DCOM- 20200708
LR  - 20200708
IS  - 1749-6632 (Electronic)
IS  - 0077-8923 (Linking)
VI  - 1463
IP  - 1
DP  - 2020 Mar
TI  - Metformin promotes mitophagy in mononuclear cells: a potential in vitro model for 
      unraveling metformin's mechanism of action.
PG  - 23-36
LID - 10.1111/nyas.14141 [doi]
AB  - Increased oxidative stress in patients with type 2 diabetes mellitus (T2DM) 
      results in abnormalities in cell repair processes, such as mitophagy, which 
      compromises mitochondrial function and contributes to insulin resistance and beta 
      cell failure. Metformin, widely recommended in the management of T2DM, exerts its 
      pleiotropic effects via 5'-AMP-activated protein kinase (AMPK); however, its 
      effect on mitophagy remains elusive. Recent evidence demonstrates that peripheral 
      blood mononuclear cells (PBMCs) express insulin receptors and the human organic 
      cation transporter protein, and they are extensively being used as a surrogate 
      for examining mitochondrial function in T2DM. Metformin treatment increased the 
      formation of acidic vesicles and mitophagosomes, upregulated mitophagy markers, 
      and enhanced mitophagic flux, as indicated by increased LC3-II expression and 
      reduced p62 protein levels. In addition, pretreatment with compound C (an AMPK 
      inhibitor) significantly decreased the expression of mitophagy markers in 
      metformin-treated cells, indicating that metformin induces mitophagy via the AMPK 
      pathway. In conclusion, metformin-induced mitophagy may improve cellular 
      function, including in beta cells, by restoring normal mitochondrial phenotype, 
      which may prove beneficial in patients with T2DM and other mitochondrial-related 
      diseases. Moreover, PBMCs may be used as a novel diagnostic biomarker for 
      identifying mitochondrial disorders.
CI  - (c) 2019 New York Academy of Sciences.
FAU - Bhansali, Shipra
AU  - Bhansali S
AD  - Department of Experimental Medicine and Biotechnology, Postgraduate Institute of 
      Medical Education and Research (PGIMER), Chandigarh, India.
FAU - Bhansali, Anil
AU  - Bhansali A
AD  - Department of Endocrinology, Postgraduate Institute of Medical Education and 
      Research (PGIMER), Chandigarh, India.
FAU - Dhawan, Veena
AU  - Dhawan V
AUID- ORCID: 0000-0001-9464-1033
AD  - Department of Experimental Medicine and Biotechnology, Postgraduate Institute of 
      Medical Education and Research (PGIMER), Chandigarh, India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190621
PL  - United States
TA  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Reactive Oxygen Species)
RN  - 9100L32L2N (Metformin)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Hypoglycemic Agents/*pharmacology
MH  - Leukocytes, Mononuclear/*drug effects/metabolism
MH  - Metformin/*pharmacology
MH  - Mitochondria/*drug effects/metabolism
MH  - Mitophagy/*drug effects/physiology
MH  - Oxidative Stress/drug effects/physiology
MH  - Reactive Oxygen Species/metabolism
OTO - NOTNLM
OT  - AMPK
OT  - PBMCs
OT  - T2DM
OT  - metformin
OT  - mitophagy
EDAT- 2019/06/22 06:00
MHDA- 2020/07/09 06:00
CRDT- 2019/06/22 06:00
PHST- 2018/09/10 00:00 [received]
PHST- 2019/03/07 00:00 [revised]
PHST- 2019/05/21 00:00 [accepted]
PHST- 2019/06/22 06:00 [pubmed]
PHST- 2020/07/09 06:00 [medline]
PHST- 2019/06/22 06:00 [entrez]
AID - 10.1111/nyas.14141 [doi]
PST - ppublish
SO  - Ann N Y Acad Sci. 2020 Mar;1463(1):23-36. doi: 10.1111/nyas.14141. Epub 2019 Jun 
      21.