LGR4 is essential for maintaining ß-cell homeostasis through suppression of RANK.
bioRxiv
; 2024 May 14.
Article
em En
| MEDLINE
| ID: mdl-38798561
ABSTRACT
Pancreatic ß-cell stress contributes to diabetes progression. This study demonstrates that Leucine-rich repeat-containing G-protein-coupled-receptor-4 (LGR4) is critical for maintaining ß-cell health and is modulated by stressors. In vitro , Lgr4 knockdown decreases proliferation and survival in rodent ß-cells, while overexpression protects against cytokine-induced cell death in rodent and human ß-cells. Mechanistically, LGR4 suppresses Receptor Activator of Nuclear Factor Kappa B (NFκB) (RANK) and its subsequent activation of NFκB to protect ß-cells. ß-cell-specific Lgr4 -conditional knockout (cko) mice exhibit normal glucose homeostasis but increased ß-cell death in both sexes and decreased proliferation only in females. Male Lgr4 cko mice under stress display reduced ß-cell proliferation and a further increase in ß-cell death. Upon aging, both male and female Lgr4 cko mice display impaired ß-cell homeostasis, however, only female mice are glucose intolerant with decreased plasma insulin. We show that LGR4 is required for maintaining ß-cell health under basal and stress-induced conditions, through suppression of RANK. Teaser LGR4 receptor is critical for maintaining ß-cell health under basal and stressed conditions, through suppression of RANK.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
BioRxiv
Ano de publicação:
2024
Tipo de documento:
Article