Glutamate Cysteine Ligase-Modulatory Subunit Knockout Mouse Shows Normal Insulin Sensitivity but Reduced Liver Glycogen Storage.

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Etat: Public
Version: Final published version
ID Serval
serval:BIB_4E1996DE9953
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Glutamate Cysteine Ligase-Modulatory Subunit Knockout Mouse Shows Normal Insulin Sensitivity but Reduced Liver Glycogen Storage.
Périodique
Frontiers in Physiology
Auteur(s)
Lavoie S., Steullet P., Kulak A., Preitner F., Do K.Q., Magistretti P.J.
ISSN
1664-042X (Electronic)
ISSN-L
1664-042X
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
7
Pages
142
Langue
anglais
Résumé
Glutathione (GSH) deficits have been observed in several mental or degenerative illness, and so has the metabolic syndrome. The impact of a decreased glucose metabolism on the GSH system is well-known, but the effect of decreased GSH levels on the energy metabolism is unclear. The aim of the present study was to investigate the sensitivity to insulin in the mouse knockout (KO) for the modulatory subunit of the glutamate cysteine ligase (GCLM), the rate-limiting enzyme of GSH synthesis. Compared to wildtype (WT) mice, GCLM-KO mice presented with reduced basal plasma glucose and insulin levels. During an insulin tolerance test, GCLM-KO mice showed a normal fall in glycemia, indicating normal insulin secretion. However, during the recovery phase, plasma glucose levels remained lower for longer in KO mice despite normal plasma glucagon levels. This is consistent with a normal counterregulatory hormonal response but impaired mobilization of glucose from endogenous stores. Following a resident-intruder stress, during which stress hormones mobilize glucose from hepatic glycogen stores, KO mice showed a lower hyperglycemic level despite higher plasma cortisol levels when compared to WT mice. The lower hepatic glycogen levels observed in GCLM-KO mice could explain the impaired glycogen mobilization following induced hypoglycemia. Altogether, our results indicate that reduced liver glycogen availability, as observed in GCLM-KO mice, could be at the origin of their lower basal and challenged glycemia. Further studies will be necessary to understand how a GSH deficit, typically observed in GCLM-KO mice, leads to a deficit in liver glycogen storage.
Mots-clé
glutathione, GCLM knockout, glycogen, insulin, glycemia, resident-intruder stress, cortisol
Pubmed
Web of science
Open Access
Oui
Création de la notice
29/05/2016 14:31
Dernière modification de la notice
20/08/2019 14:03
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