The biguanide metformin is the most commonly used antidiabetic drug. Recent studies show that metformin not only improves chronic inflammation by improving metabolic parameters but also has a direct anti-inflammatory effect. In light of these findings, it is essential to identify the inflammatory pathways targeted by metformin to develop a comprehensive understanding of the mechanisms of action of this drug. Commonly accepted mechanisms of metformin action include AMPK activation and inhibition of mTOR pathways, which are evaluated in multiple diseases. Additionally, metformin’s action on mitochondrial function and cellular homeostasis processes such as autophagy is of particular interest because of the importance of these mechanisms in maintaining cellular health. Both dysregulated mitochondria and failure of the autophagy pathways, the latter of which impair clearance of dysfunctional, damaged, or excess organelles, affect cellular health drastically and can trigger the onset of metabolic and age-related diseases. Immune cells are the fundamental cell types that govern the health of an organism. Thus, dysregulation of autophagy or mitochondrial function in immune cells has a remarkable effect on susceptibility to infections, response to vaccination, tumor onset, and the development of inflammatory and autoimmune conditions. In this study, we summarize the latest research on metformin’s regulation of immune cell mitochondrial function and autophagy as evidence that new clinical trials on metformin with primary outcomes related to the immune system should be considered to treat immune-mediated diseases over the near term.
|American Journal of Physiology - Cell Physiology
|Published - May 2021
Bibliographical noteFunding Information:
This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant R01DK108056 (to B.S.N.), National Institute on Aging Grant R56AG069685 (to B.S.N.), and the College of Health Sciences, Faculty Development Grant (to L.P.B.).
Copyright © 2021 the American Physiological Society
- Complex 1
ASJC Scopus subject areas
- Cell Biology