Bioenergetic bypass using cell-permeable succinate, but not methylene blue, attenuates metformin-induced lactate production.

ABSTRACT:

Background

Metformin is the most common pharmacological treatment for type 2 diabetes. It is considered safe but has been associated with the development of lactic acidosis under circumstances where plasma concentrations exceed therapeutic levels. Metformin-induced lactic acidosis has been linked to the drug's toxic effect on mitochondrial function. Current treatment strategies aim to remove the drug and correct for the acidosis. With a mortality of 20%, complementary treatment strategies are needed. In this study, it was investigated whether targeting mitochondria with pharmacological agents that bypass metformin-induced mitochondrial dysfunction can counteract the energetic deficit linked to toxic doses of metformin.

Methods

The redox agent methylene blue and the cell-perm

SUBMITTER: Piel S 

PROVIDER: S-EPMC6070446 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature