New mechanisms of metformin action: Focusing on mitochondria and the gut

Journal of Diabetes Investigation

Kyu Yeon Hur¹ 

[1]Division of Endocrinology & Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

关键词: Autophagy;    Gut;    Mitochondria;   

DOI  :  10.1111/jdi.12328

来源: Wiley

【 摘 要 】

Abstract

The most well-known mechanism of metformin action, one of the most commonly prescribed antidiabetic drugs, is adenosine monophosphate-activated protein kinase activation; however, recent investigations have shown that adenosine monophosphate-activated protein kinase-independent pathways can explain some of metformin's beneficial metabolic effects as well as undesirable side-effects. Such novel pathways include induction of mitochondrial stress, inhibition of mitochondrial shuttles, alteration of intestinal microbiota, suppression of glucagon signaling, activation of autophagy, attenuation of inflammasome activation, induction of incretin receptors and reduction of terminal endoplasmic reticulum stress. Together, these studies have broadened our understanding of the mechanisms of antidiabetic agents as well as the pathogenic mechanism of diabetes itself. The results of such investigations might help to identify new target molecules and pathways for treatment of diabetes and metabolic syndrome, and could also have broad implications in diseases other than diabetes. Accordingly, new antidiabetic drugs with better efficacy and fewer adverse effects will likely result from these studies.

【 授权许可】

CC BY-NC-ND   
© 2015 The Authors. Journal of Diabetes Investigation published by Asian Association of the Study of Diabetes (AASD) and Wiley Publishing Asia Pty Ltd

Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.