Growth differentiation factor-15 prevents glucotoxicity and connexin-36 downregulation in pancreatic beta-cells.
Animals
Cell Survival
/ drug effects
Cells, Cultured
Connexins
/ genetics
Cytoprotection
/ genetics
Down-Regulation
/ drug effects
Glucose
/ adverse effects
Growth Differentiation Factor 15
/ genetics
Insulin
/ metabolism
Insulin Secretion
/ drug effects
Insulin-Secreting Cells
/ drug effects
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Gap Junction delta-2 Protein
Connexin-36
GDF15
Glucotoxicity
INS-1E
Pancreatic beta-cell dysfunction
Journal
Molecular and cellular endocrinology
ISSN: 1872-8057
Titre abrégé: Mol Cell Endocrinol
Pays: Ireland
ID NLM: 7500844
Informations de publication
Date de publication:
05 02 2022
05 02 2022
Historique:
received:
22
02
2021
revised:
26
10
2021
accepted:
29
10
2021
pubmed:
12
11
2021
medline:
29
3
2022
entrez:
11
11
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34763008
pii: S0303-7207(21)00347-6
doi: 10.1016/j.mce.2021.111503
pii:
doi:
Substances chimiques
Connexins
0
Gdf15 protein, mouse
0
Growth Differentiation Factor 15
0
Insulin
0
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
111503Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.