Growth differentiation factor-15 prevents glucotoxicity and connexin-36 downregulation in pancreatic beta-cells.
Mol Cell Endocrinol
; 541: 111503, 2022 02 05.
Article
de En
| MEDLINE
| ID: mdl-34763008
ABSTRACT
Pancreatic beta cell dysfunction is a hallmark of type 2 diabetes. Growth differentiation factor 15 (GDF15), which is an energy homeostasis regulator, has been shown to improve several metabolic parameters in the context of diabetes. However, its effects on pancreatic beta-cell remain to be identified. We, therefore, performed experiments using cell models and histological sectioning of wild-type and knock-out GDF15 mice to determine the effect of GDF15 on insulin secretion and cell viability. A bioinformatics analysis was performed to identify GDF15-correlated genes. GDF15 prevents glucotoxicity-mediated altered glucose-stimulated insulin secretion (GSIS) and connexin-36 downregulation. Inhibition of endogenous GDF15 reduced GSIS in cultured mouse beta-cells under standard conditions while it had no impact on GSIS in cells exposed to glucolipotoxicity, which is a diabetogenic condition. Furthermore, this inhibition exacerbated glucolipotoxicity-reduced cell survival. This suggests that endogenous GDF15 in beta-cell is required for cell survival but not GSIS in the context of glucolipotoxicity.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Connexines
/
Cellules à insuline
/
Facteur-15 de croissance et de différenciation
/
Glucose
Type d'étude:
Prognostic_studies
Limites:
Animals
Langue:
En
Journal:
Mol Cell Endocrinol
Année:
2022
Type de document:
Article
Pays d'affiliation:
Suisse