PMID- 34281285
OWN - NLM
STAT- MEDLINE
DCOM- 20210726
LR  - 20211204
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 13
DP  - 2021 Jul 5
TI  - Metformin as a Treatment Strategy for Sjogren's Syndrome.
LID - 10.3390/ijms22137231 [doi]
LID - 7231
AB  - Sjogren's syndrome (SS), a chronic inflammatory disease involving the salivary 
      and lacrimal glands, presents symptoms of sicca as well as systemic 
      manifestations such as fatigue and musculoskeletal pain. Only a few treatments 
      have been successful in management of SS; thus treatment of the disease is 
      challenging. Metformin is the first-line agent for type 2 diabetes and has 
      anti-inflammatory potential. Its immunomodulatory capacity is exerted via 
      activation of 5' adenosine monophosphate-activated protein kinase (AMPK). 
      Metformin inhibits mitochondrial respiratory chain complex I which leads to 
      change in adenosine mono-phosphate (AMP) to adenosine tri-phosphate (ATP) ratio. 
      This results in AMPK activation and causes inhibition of mammalian target of 
      rapamycin (mTOR). mTOR plays an important role in T cell differentiation and mTOR 
      deficient T cells differentiate into regulatory T cells. In this manner, 
      metformin enhances immunoregulatory response in an individual. mTOR is 
      responsible for B cell proliferation and germinal center (GC) differentiation. 
      Thus, reduction of B cell differentiation into antibody-producing plasma cells 
      occurs via downregulation of mTOR. Due to the lack of suggested treatment for SS, 
      metformin has been considered as a treatment strategy and is expected to 
      ameliorate salivary gland function.
FAU - Kim, Joa
AU  - Kim J
AD  - Division of Rheumatology, Department of Internal Medicine, Chosun University 
      Hospital, Gwangju 61453, Korea.
FAU - Kim, Yun-Sung
AU  - Kim YS
AD  - Division of Rheumatology, Department of Internal Medicine, Chosun University 
      Hospital, Gwangju 61453, Korea.
FAU - Park, Sung-Hwan
AU  - Park SH
AD  - Division of Rheumatology, Department of Internal Medicine, College of Medicine, 
      The Catholic University of Korea, Seoul 06591, Korea.
LA  - eng
GR  - HI20C1496/Ministry of Health & Welfare, Republic of Korea/
PT  - Journal Article
PT  - Review
DEP - 20210705
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Immunologic Factors)
RN  - 9100L32L2N (Metformin)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
MH  - B-Lymphocytes/drug effects/immunology
MH  - Gastrointestinal Microbiome/drug effects/immunology
MH  - Humans
MH  - Immunologic Factors/therapeutic use
MH  - Macrophages/drug effects/immunology
MH  - Metformin/*therapeutic use
MH  - Signal Transduction/drug effects
MH  - Sjogren's Syndrome/*drug therapy/etiology/physiopathology
MH  - T-Lymphocytes/drug effects/immunology
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC8269365
OTO - NOTNLM
OT  - AMPK/mTOR pathway
OT  - Sjogren's syndrome
OT  - metformin
COIS- The authors declare no conflict of interest.
EDAT- 2021/07/21 06:00
MHDA- 2021/07/27 06:00
PMCR- 2021/07/05
CRDT- 2021/07/20 01:03
PHST- 2021/06/06 00:00 [received]
PHST- 2021/06/25 00:00 [revised]
PHST- 2021/06/30 00:00 [accepted]
PHST- 2021/07/20 01:03 [entrez]
PHST- 2021/07/21 06:00 [pubmed]
PHST- 2021/07/27 06:00 [medline]
PHST- 2021/07/05 00:00 [pmc-release]
AID - ijms22137231 [pii]
AID - ijms-22-07231 [pii]
AID - 10.3390/ijms22137231 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Jul 5;22(13):7231. doi: 10.3390/ijms22137231.