Probably the most common mechanism by which metformin elevates blood lactate is by inducing catecholamine release in those who regulate or prescribe it. Caution in restricting the use of metformin for the treatment of type 2 diabetes has been rationalized on the basis of J) its chemical identity as a biguanide, 2) its ability to modify hepatic intermediary metabolism, 3) its administration to i...

AMP-activated protein kinase (AMPK) acts as a cellular energy sensor: it responds to an increase in AMP concentration ([AMP]) or the AMP-to-ATP ratio (AMP/ATP). Metformin and phenformin, which are biguanides, have been reported to increase AMPK activity without increasing AMP/ATP. This study tests the hypothesis that these biguanides increase AMPK activity in the heart by increasing cytosolic [...

Rapidly growing glycolytic tumors require energy and intracellular pH (pHi) homeostasis through the activity of two major monocarboxylate transporters, MCT1 and the hypoxia-inducible MCT4, in intimate association with the glycoprotein CD147/BASIGIN (BSG). To further explore and validate the blockade of lactic acid export as an anticancer strategy, we disrupted, via zinc finger nucleases, MCT4 a...

Adaptive cellular responses resulting from multiple microenvironmental stresses, such as hypoxia and nutrient deprivation, are potential novel drug targets for cancer treatment. Accordingly, we focused on developing anticancer agents targeting the tumor microenvironment (TME). In this study, to search for selective antitumor agents blocking adaptive responses in the TME, thirteen new compounds,...

In the present study, we investigated the anticancer effects of the mitochondrial inhibitors, metaiodobenzylguanidine (MIBG), metformin and phenformin. 131I-MIBG has been used for scintigraphic detection and the targeted radiotherapy of neuroblastoma (NB), a pediatric malignancy. Non-radiolabeled MIBG has been reported to be cytotoxic to NB cells in vitro and in vivo. However, the mechanisms be...

and metformin (dimethylbiguanide), have been linked to lac tic ac i do sis (LA), a met a bolic con di tion as so ci ated with high rate of mor tal ity. Phenformin was dis con tin ued in the United States (U.S.) in 1976 due to sus pected as so ci a tion with LA. Metformin, a mod i fied biguanide, has been widely used out side the U.S., with con sid er ably fewer re ported cases of LA than were r...