Dipeptidyl peptidase-4 (DPP4) inhibitor sitagliptin alleviates liver inflammation of diabetic mice by acting as a ROS scavenger and inhibiting the NFκB pathway.
Journal
Cell death discovery
ISSN: 2058-7716
Titre abrégé: Cell Death Discov
Pays: United States
ID NLM: 101665035
Informations de publication
Date de publication:
07 Sep 2021
07 Sep 2021
Historique:
received:
29
07
2021
accepted:
19
08
2021
revised:
09
08
2021
entrez:
8
9
2021
pubmed:
9
9
2021
medline:
9
9
2021
Statut:
epublish
Résumé
As a common chronic metabolic disease, the development of diabetes mellitus (DM) may also be accompanied by liver damage and inflammatory disorders. Sitagliptin is an inhibitor of dipeptidyl peptidase-4 (DPP4, also known as CD26), which is clinically used for DM treatment. However, the mechanism of sitagliptin's efficiency in liver diseases is largely unknown. In this study, mice suffering from streptozotocin (STZ) exhibit elevated liver DPP4 expression and activity, as well as inflammatory and chronic liver injury phenotype, whereas specifically inhibiting the activity of DPP4 in mouse liver tissues and hepatocytes by sitagliptin contributes to decreased cytokines, oxidative stress, cell apoptosis, and inflammation in STZ-induced diabetic mice. Moreover, sitagliptin reduced TNFα or LPS-induced cellular reactive oxygen species (ROS) level, cell apoptosis, and protein expression in the NFκB signaling pathway in HepG2 cells or primary mouse hepatocytes. Altogether, our study confirms that sitagliptin may protect liver tissue by alleviating ROS production and NFκB signaling activation, providing a putative mechanism for preventing the development of diabetic liver disease.
Identifiants
pubmed: 34493714
doi: 10.1038/s41420-021-00625-7
pii: 10.1038/s41420-021-00625-7
pmc: PMC8423797
doi:
Types de publication
Journal Article
Langues
eng
Pagination
236Subventions
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 81800723
Informations de copyright
© 2021. The Author(s).
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