The antianginal ranolazine fails to improve glycaemia in obese liver-specific pyruvate dehydrogenase deficient male mice.
hepatic steatosis
non-alcoholic fatty liver disease
obesity
pyruvate dehydrogenase
ranolazine
Journal
Basic & clinical pharmacology & toxicology
ISSN: 1742-7843
Titre abrégé: Basic Clin Pharmacol Toxicol
Pays: England
ID NLM: 101208422
Informations de publication
Date de publication:
Aug 2023
Aug 2023
Historique:
revised:
25
04
2023
received:
24
01
2023
accepted:
08
05
2023
medline:
6
7
2023
pubmed:
3
6
2023
entrez:
3
6
2023
Statut:
ppublish
Résumé
Recent studies have demonstrated that stimulating pyruvate dehydrogenase (PDH, gene Pdha1), the rate-limiting enzyme of glucose oxidation, can reverse obesity-induced non-alcoholic fatty liver disease (NAFLD), which can be achieved via treatment with the antianginal ranolazine. Accordingly, our aim was to determine whether ranolazine's ability to mitigate obesity-induced NAFLD and hyperglycaemia requires increases in hepatic PDH activity. We generated liver-specific PDH-deficient (Pdha1 Pdha1 Liver-specific PDH deficiency is insufficient to promote an NAFLD phenotype. Nonetheless, hepatic PDH activity partially contributes to how the antianginal ranolazine improves glucose tolerance and alleviates hepatic steatosis in obesity.
Substances chimiques
Glucose
IY9XDZ35W2
Oxidoreductases
EC 1.-
Ranolazine
A6IEZ5M406
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
194-201Subventions
Organisme : CIHR
Pays : Canada
Organisme : CIHR
Pays : Canada
Informations de copyright
© 2023 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).
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