Metformin as a Treatment Strategy for Sjögren's Syndrome

Int J Mol Sci. 2021 Jul 5;22(13):7231. doi: 10.3390/ijms22137231.

Abstract

Sjögren'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.

Keywords: AMPK/mTOR pathway; Sjögren’s syndrome; metformin.

Publication types

  • Review

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • Gastrointestinal Microbiome / drug effects
  • Gastrointestinal Microbiome / immunology
  • Humans
  • Immunologic Factors / therapeutic use
  • Macrophages / drug effects
  • Macrophages / immunology
  • Metformin / therapeutic use*
  • Signal Transduction / drug effects
  • Sjogren's Syndrome / drug therapy*
  • Sjogren's Syndrome / etiology
  • Sjogren's Syndrome / physiopathology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Immunologic Factors
  • Metformin
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinases