Open AccessNew mechanisms of metformin action: Focusing on mitochondria and the gut
Author(s) -
Hur Kyu Yeon,
Lee MyungShik
Publication year - 2015
Publication title -
journal of diabetes investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.089
H-Index - 50
eISSN - 2040-1124
pISSN - 2040-1116
DOI - 10.1111/jdi.12328
Subject(s) - metformin , medicine , adenosine , autophagy , ampk , signal transduction , inflammasome , pharmacology , diabetes mellitus , protein kinase a , mitochondrion , microbiology and biotechnology , receptor , kinase , endocrinology , biology , biochemistry , apoptosis
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.