Metformin inhibits digestive proteases and impairs protein digestion in mice.
J Biol Chem
; 299(12): 105363, 2023 Dec.
Article
em En
| MEDLINE
| ID: mdl-37863262
ABSTRACT
Metformin is among the most prescribed medications worldwide and the first-line therapy for type 2 diabetes. However, gastrointestinal side effects are common and can be dose limiting. The total daily metformin dose frequently reaches several grams, and poor absorption results in high intestinal drug concentrations. Here, we report that metformin inhibits the activity of enteropeptidase and other digestive enzymes at drug concentrations predicted to occur in the human duodenum. Treatment of mouse gastrointestinal tissue with metformin reduces enteropeptidase activity; further, metformin-treated mice exhibit reduced enteropeptidase activity, reduced trypsin activity, and impaired protein digestion within the intestinal lumen. These results indicate that metformin-induced protein maldigestion could contribute to the gastrointestinal side effects and other impacts of this widely used drug.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Enteropeptidase
/
Proteólise
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Metformina
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article