Insights into the action of the pharmaceutical metformin: Targeted inhibition of the gut microbial enzyme agmatinase.

ABSTRACT: Metformin is the first-line treatment for type 2 diabetes, yet its mechanism of action is not fully understood. Recent studies suggest metformin's interactions with gut microbiota are responsible for exerting therapeutic effects. In this study, we report that metformin targets the gut microbial enzyme agmatinase, as a competitive inhibitor, which may impair gut agmatine catabolism. The metformin inhibition constant (K_i) of E. coli agmatinase is 1 mM and relevant in the gut where the drug concentration is 1-10 mM. Metformin analogs phenformin, buformin, and galegine are even more potent inhibitors of E. coli agmatinase (K_i = 0.6, 0.1, and 0.007 mM, respectively) suggesting a shared mechanism. Agmatine is a known effector of human host metabolism and has b

SUBMITTER: Tassoulas LJ 

PROVIDER: S-EPMC10839685 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature