Amino acid homeostasis is a target of metformin therapy.

ABSTRACT:

Objective

Unexplained changes in regulation of branched chain amino acids (BCAA) during diabetes therapy with metformin have been known for years. Here we have investigated mechanisms underlying this effect.

Methods

We used cellular approaches, including single gene/protein measurements, as well as systems-level proteomics. Findings were then cross-validated with electronic health records and other data from human material.

Results

In cell studies, we observed diminished uptake/incorporation of amino acids following metformin treatment of liver cells and cardiac myocytes. Supplementation of media with amino acids attenuated known effects of the drug, including on glucose production, providing a possible explanation for discrepancies between effective doses in vivo and

SUBMITTER: Forteath C 

PROVIDER: S-EPMC10328998 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature