Growth differentiation factor-15 prevents glucotoxicity and connexin-36 downregulation in pancreatic beta-cells.
Mol Cell Endocrinol
; 541: 111503, 2022 02 05.
Article
en 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.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Conexinas
/
Células Secretoras de Insulina
/
Factor 15 de Diferenciación de Crecimiento
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Glucosa
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Mol Cell Endocrinol
Año:
2022
Tipo del documento:
Article