biostudies-literatureUnknown150(8)Hinke SA<h4>Background and purpose</h4>Two mechanisms have been proposed to explain the insulin-sensitising properties of metformin in peripheral tissues: (a) inhibition of electron transport chain complex I, and (b) activation of the AMP activated protein kinase (AMPK). However the relationship between these mechanisms and their contribution to beta-cell death and dysfunction in vitro, are currently unclear.<h4>Experimental approach</h4>The effects of biguanides (metformin and phenformin) were tested on MIN6 beta-cells and primary FACS-purified rat beta-cells. Cell metabolism was assessed biochemically and by FACS analysis, and correlated with AMPK phosphorylation state and cell viability, with or without fuel substrates.<h4>Key results</h4>In MIN6 cells, metformin reduced mitochondrial complex IBritish journal of pharmacology1031-43https://www.ebi.ac.uk/biostudies/studies/S-EPMC2013909biostudies-literatureMethyl succinate antagonises biguanide-induced AMPK-activation and death of pancreatic beta-cells through restoration of mitochondrial electron transfer.PMC2013909Heimberg HCai YVan de Casteele MMartens GAHinke SAPipeleers DFinsi JfalseMethyl succinate antagonises biguanide-induced AMPK-activation and death of pancreatic beta-cells through restoration of mitochondrial electron transfer.<h4>Background and purpose</h4>Two mechanisms have been proposed to explain the insulin-sensitising properties of metformin in peripheral tissues: (a) inhibition of electron transport chain complex I, and (b) activation of the AMP activated protein kinase (AMPK). However the relationship between these mechanisms and their contribution to beta-cell death and dysfunction in vitro, are currently unclear.<h4>Experimental approach</h4>The effects of biguanides (metformin and phenformin) were tested on MIN6 beta-cells and primary FACS-purified rat beta-cells. Cell metabolism was assessed biochemically and by FACS analysis, and correlated with AMPK phosphorylation state and cell viability, with or without fuel substrates.<h4>Key results</h4>In MIN6 cells, metformin reduced mitochondrial complex I2007-01-01T00:00:00Z2007 Apr2025-04-04T18:41:52.384Z2019-03-27T02:21:40ZS-EPMC20139091733983310.1038/sj.bjp.0707189