Metformin inhibits digestive proteases and impairs protein digestion in mice.
diabetes
enteropeptidase
intestine
maldigestion
metformin
protease
protein degradation
trypsin
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
19 Oct 2023
19 Oct 2023
Historique:
received:
09
08
2023
revised:
29
09
2023
accepted:
11
10
2023
pubmed:
21
10
2023
medline:
21
10
2023
entrez:
20
10
2023
Statut:
aheadofprint
Résumé
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.
Identifiants
pubmed: 37863262
pii: S0021-9258(23)02391-8
doi: 10.1016/j.jbc.2023.105363
pmc: PMC10663847
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
105363Subventions
Organisme : NCCIH NIH HHS
ID : R01 AT010014
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM118159
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR026992
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK007017
Pays : United States
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest The authors declare no conflicts of interest with the contents of this article.
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