Short-and long-term administration of imeglimin counters cardiorenal dysfunction in a rat model of metabolic syndrome.
cardiomyopathy
imeglimin
rat
type‐2 diabetes
Journal
Endocrinology, diabetes & metabolism
ISSN: 2398-9238
Titre abrégé: Endocrinol Diabetes Metab
Pays: England
ID NLM: 101732442
Informations de publication
Date de publication:
Jul 2020
Jul 2020
Historique:
received:
02
10
2019
revised:
06
03
2020
accepted:
07
03
2020
entrez:
25
7
2020
pubmed:
25
7
2020
medline:
25
7
2020
Statut:
epublish
Résumé
Imeglimin, a glucose-lowering agent targeting mitochondrial bioenergetics, decreases reactive oxygen species (ROS) overproduction and improves glucose homeostasis. We investigated whether this is associated with protective effects on metabolic syndrome-related left ventricular (LV) and vascular dysfunctions. We used Zucker Compared to untreated animals, 9- and 90-day imeglimin treatment decreased LV end-diastolic pressure and LV end-diastolic pressure-volume relation, increased LV tissue perfusion and decreased LV ROS production. Simultaneously, imeglimin restored acetylcholine-mediated coronary relaxation and mesenteric flow-mediated dilation. One hour after imeglimin administration, when glucose plasma levels were not yet modified, imeglimin reduced LV mitochondrial ROS production and improved LV function. Ninety-day imeglimin treatment reduced related LV and kidney fibrosis and improved kidney function. In a rat model, mimicking Human metabolic syndrome, imeglimin immediately countered metabolic syndrome-related cardiac diastolic and vascular dysfunction by reducing oxidative stress/increased NO bioavailability and improving myocardial perfusion and after 90-day treatment myocardial and kidney structure, effects that are, at least in part, independent from glucose control.
Identifiants
pubmed: 32704553
doi: 10.1002/edm2.128
pii: EDM2128
pmc: PMC7375119
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e00128Informations de copyright
© 2020 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.
Déclaration de conflit d'intérêts
Marianne Lachaux, Matthieu Soulié, Mouad Hamzaoui, Anaëlle Bailly, Lionel Nicol, Isabelle Rémy‐Jouet, Sylvanie Renet, Cathy Vendeville, Christelle Monteil, Vincent Richard and Paul Mulder (being the guarantor) have nothing to declare. Pascale Gluais‐Dagorn and Sophie Hallakou‐Bozec are employee Poxel SA.
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