Differential sensitivity of human islets from obese versus lean donors to chronic high glucose or palmitate.

Détails

ID Serval
serval:BIB_0F8F92DBC03A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Differential sensitivity of human islets from obese versus lean donors to chronic high glucose or palmitate.
Périodique
Journal of diabetes
Auteur⸱e⸱s
Castex F., Leroy J., Broca C., Mezghenna K., Duranton F., Lavallard V., Lebreton F., Gross R., Wojtusciszyn A., Lajoix A.D.
ISSN
1753-0407 (Electronic)
ISSN-L
1753-0407
Statut éditorial
Publié
Date de publication
07/2020
Peer-reviewed
Oui
Volume
12
Numéro
7
Pages
532-541
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Due to the shortage of multi-organ donors, human pancreatic islet transplantation has now been extended to islets originating from obese subjects. In this study, our aim is to compare the respective sensitivity of human islets from lean vs obese donors to chronic high glucose or high palmitate.
Human islets were isolated from pancreases harvested from brain-dead multi-organ donors. Islets were cultured during 72 hours in the presence of moderate (16.7 mmol/L) or high (28 mmoL/L) glucose concentrations, or glucose (5.6 mmoL/L) and palmitate (0.4 mmoL/L), before measurement of their response to glucose.
We first observed a greater insulin response in islets from obese donors under both basal and high-glucose conditions, confirming their hyperresponsiveness to glucose. When islets from obese donors were cultured in the presence of moderate or high glucose concentrations, insulin response to glucose remained unchanged or was slightly reduced, as opposed to that observed in lean subjects. Moreover, culturing islets from obese donors with high palmitate also induced less reduction in insulin response to glucose than in lean subjects. This partial protection of obese islets is associated with less induction of inducible nitric oxide synthase in islets, together with a greater expression of the transcription factor forkhead box O1 (FOXO1).
Our data suggest that in addition to an increased sensitivity to glucose, islets from obese subjects can be considered as more resistant to glucose and fatty acid excursions and are thus valuable candidates for transplantation.
Mots-clé
Aged, Glucose/pharmacology, Humans, Insulin Secretion/drug effects, Islets of Langerhans/drug effects, Islets of Langerhans/metabolism, Male, Middle Aged, Obesity/metabolism, Palmitates/pharmacology, human islets, insulin secretion, islet transplantation, nitric oxide synthase, obesity, 一氧化氮合成酶, 人胰岛, 肥胖, 胰岛移植, 胰岛素分泌
Pubmed
Web of science
Création de la notice
14/06/2021 9:58
Dernière modification de la notice
24/05/2024 12:47
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