Proteomics-Based Analysis of Metformin Hydrochloride for Modulating Butanoate Metabolism in Diabetic Kidney Disease
Chai J, et al. Analysis, 2025, 254, 116584.
In this study, metformin hydrochloride was evaluated for its mechanistic role in diabetic kidney disease (DKD) through proteomics and bioinformatics approaches. Kidney tissues from db/db mice were analyzed post-treatment to identify differential protein expression patterns. Mass spectrometry-based proteomic profiling revealed significant alterations in proteins associated with the butanoate metabolism pathway, notably AACS, ACSM3, EHHADH, and HMGCS2. Bioinformatics analysis further confirmed strong molecular interactions between metformin and these proteins (binding energies < -5 kcal/mol), suggesting direct regulatory effects. These findings imply that metformin may exert renoprotective effects by modulating mitochondrial energy metabolism and inflammatory responses via the butanoate pathway, offering insights into its therapeutic action beyond glycemic control. This experimental approach underscores the utility of integrative proteomics in elucidating drug mechanisms in complex metabolic diseases.