Biological Characterization of Gene Response to Insulin-Induced Hypoglycemia in Mouse Retina.

Détails

Ressource 1Télécharger: BIB_147AACF8356C.P001.pdf (2092.77 [Ko])
Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_147AACF8356C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Biological Characterization of Gene Response to Insulin-Induced Hypoglycemia in Mouse Retina.
Périodique
Plos One
Auteur(s)
Emery M., Nanchen N., Preitner F., Ibberson M., Roduit R.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
11
Numéro
2
Pages
e0150266
Langue
anglais
Notes
Publication types: Journal Article Publication Status: epublish
Résumé
Glucose is the most important metabolic substrate of the retina and maintenance of normoglycemia is an essential challenge for diabetic patients. Chronic, exaggerated, glycemic excursions could lead to cardiovascular diseases, nephropathy, neuropathy and retinopathy. We recently showed that hypoglycemia induced retinal cell death in mouse via caspase 3 activation and glutathione (GSH) decrease. Ex vivo experiments in 661W photoreceptor cells confirmed the low-glucose induction of death via superoxide production and activation of caspase 3, which was concomitant with a decrease of GSH content. We evaluate herein retinal gene expression 4 h and 48 h after insulin-induced hypoglycemia. Microarray analysis demonstrated clusters of genes whose expression was modified by hypoglycemia and we discuss the potential implication of those genes in retinal cell death. In addition, we identify by gene set enrichment analysis, three important pathways, including lysosomal function, GSH metabolism and apoptotic pathways. Then we tested the effect of recurrent hypoglycemia (three successive 4h periods of hypoglycemia spaced by 48 h recovery) on retinal cell death. Interestingly, exposure to multiple hypoglycemic events prevented GSH decrease and retinal cell death, or adapted the retina to external stress by restoring GSH level comparable to control situation. We hypothesize that scavenger GSH is a key compound in this apoptotic process, and maintaining "normal" GSH level, as well as a strict glycemic control, represents a therapeutic challenge in order to avoid side effects of diabetes, especially diabetic retinopathy.
Pubmed
Web of science
Open Access
Oui
Création de la notice
27/02/2016 14:15
Dernière modification de la notice
20/08/2019 12:43
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