Regulation of organelle function by metformin

Abstract

Metformin ameliorates hyperglycemia without the side effects of lactic acidosis or hypoglycemia. Metformin lowers the blood glucose level by decreasing hepatic glucose production in the liver and by increasing glucose uptake in the muscle. Recent studies show that metformin induces cell death in certain cancer cell lines by interfering with the metabolism of the cancer cells. Therefore, understanding the mechanisms of action for metformin will provide insights into how to better treat diabetes and other metabolic disorders and also into the development of new therapeutic drugs. One of the best understood molecular targets of metformin is the mitochondrial complex I. However, given metformin's broad effects on metabolism, it could act on multiple targets. In this review, we summarize current findings in metformin's mechanisms of action regarding its known targets in mitochondria and known effects in cancer cell lines. Then, we introduce endosomal Na /H exchangers and the V-ATPase as new potential targets of metformin's action. Finally, we will discuss the hypothesis that metformin directly acts on endosome/lysosome regulation so as to regulate metabolism and ultimately alleviate type 2 diabetes. © 2017 IUBMB Life, 69(7):459-469, 2017.

Mitochondrial Dysfunction in Age‐Related Metabolic Disorders

“…[ 153–156 ] In addition to AMPK activation and mTORC1 inhibition, Metformin potentially affects cell metabolism by altering the rate of endocytic cycle for mediating receptors and transporters involved in autophagy. [ 157 ] Besides Metformin, Rapamycin is known to prevent age‐related diseases but also increases mortality in mouse model of T2DM. [ 158 ] Furthermore, other compounds such as scopoletin, [ 159 ] gentiopicroside, [ 160 ] and icariside II [ 161 ] have been shown to activate AMPK.…”

Mitoprotective Clinical Strategies in Type 2 Diabetes and Fanconi Anemia Patients: Suggestions for Clinical Management of Mitochondrial Dysfunction

“…At the purpose to counteract T2D-associated OS, the use of several antioxidants was suggested [22][23][24][25][26][27][28][29][30]. Thereafter, and up to recent studies, MDF was further investigated as a salient feature of T2D, while a mechanistic role of the antidiabetic drug metformin, and of an herbal antidiabetic formulation, was associated with improvement of mitochondrial function [31][32][33].…”

Metformin inhibited colitis and colitis-associated cancer (CAC) through protecting mitochondrial structures of colorectal epithelial cells in mice

“…A number of studies suggest that the inhibition of metformin on cancer cells might associate with its activity of targeting cellular mitochondria. 11,12 It is assumed that mitochondria are the major target of metformin, leading to the inhibition of mitochondrial respiration, AMPK activation and bioenergetic reprogramming. 13 On the contrary, metformin also found to activate AMPK in cardiac myoblast H9c2 cells and many other type of normal cells like smooth muscle cells.…”