Sorcin links pancreatic β cell lipotoxicity to ER Ca2+ stores.

Détails

ID Serval
serval:BIB_FD358A981FEB
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Sorcin links pancreatic β cell lipotoxicity to ER Ca2+ stores.
Périodique
Diabetes
Auteur(s)
Marmugi A., Parnis J., Chen X., Carmichael L., Hardy J., Mannan N., Marchetti P., Piemonti L., Bosco D., Johnson P., Shapiro A.M., Cruciani-Guglielmacci C., Magnan C., Ibberson M., Thorens B., Valdivia H.H., Rutter G.A., Leclerc I.
ISSN
1939-327X (Electronic)
ISSN-L
0012-1797
Statut éditorial
Publié
Date de publication
2016
Volume
65
Numéro
4
Pages
1009-1021
Langue
anglais
Résumé
Preserving β cell function during the development of obesity and insulin resistance would limit the worldwide epidemic of type 2 diabetes (T2DM). Endoplasmic reticulum (ER) calcium (Ca(2+)) depletion induced by saturated free fatty acids and cytokines causes β cell ER stress and apoptosis, but the molecular mechanisms behind these phenomena are still poorly understood. Here, we demonstrate that palmitate-induced sorcin (SRI) down-regulation, and subsequent increases in glucose-6-phosphatase catalytic subunit-2 (G6PC2) levels contribute to lipotoxicity. SRI is a calcium sensor protein involved in maintaining ER Ca(2+) by inhibiting ryanodine receptor activity and playing a role in terminating Ca(2+)-induced Ca(2+) release. G6PC2, a GWAS gene associated with fasting blood glucose, is a negative regulator of glucose-stimulated insulin secretion (GSIS). High fat feeding in mice and chronic exposure of human islets to palmitate decreases endogenous SRI expression while levels of G6PC2 mRNA increase. Sorcin null mice are glucose intolerant, with markedly impaired GSIS and increased expression of G6pc2. Under high fat diet, mice overexpressing SRI in the β cell display improved glucose tolerance, fasting blood glucose and GSIS, whereas G6PC2 levels are decreased and cytosolic and ER Ca(2+) are increased in transgenic islets. SRI may thus provide a target for intervention in T2DM.
Pubmed
Web of science
Open Access
Oui
Création de la notice
17/02/2016 16:06
Dernière modification de la notice
20/08/2019 16:28
Données d'usage