Methyl succinate antagonises biguanide-induced AMPK-activation and death of pancreatic beta-cells through restoration of mitochondrial electron transfer.

ABSTRACT:

Background and purpose

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.

Experimental approach

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.

Key results

In MIN6 cells, metformin reduced mitochondrial complex I

SUBMITTER: Hinke SA 

PROVIDER: S-EPMC2013909 | biostudies-literature | 2007 Apr

REPOSITORIES: biostudies-literature