LGR4 is essential for maintaining β-cell homeostasis through suppression of RANK.

Objective: Loss of functional β-cell mass is a major cause of diabetes. Thus, identifying regulators of β-cell health is crucial for treating this disease. The In this study, we assessed the regulation of Lgr4 in islets, and the role of LGR4 and LGR4/RANK stoichiometry in β-cell health under basal and stress-induced conditions, in vitro and in vivo.

LGR4 is essential for maintaining β-cell homeostasis through suppression of RANK.

Unlabelled: Pancreatic β-cell stress contributes to diabetes progression. This study demonstrates that Leucine-rich repeat-containing G-protein-coupled-receptor-4 (LGR4) is critical for maintaining β-cell health and is modulated by stressors. , knockdown decreases proliferation and survival in rodent β-cells, while overexpression protects against cytokine-induced cell death in rodent and human β-cells.