Work

Circulating RANKL is required for glucose homeostasis during pregnancy

Year: 2026

Type: article

Abstract: Background Gestational diabetes mellitus (GDM) poses a significant health burden on women worldwide, necessitating the search for predictive, diagnostic and therapeutic approaches. Increasing evidence suggests that the receptor activator of NF-κB ligand (RANKL) is closely associated with GDM, and this study explored whether RANKL can be used as a biomarker for GDM. Methods We conducted a cross-sectional study on pregnant women attending prenatal examinations in China. 399 pregnancies were finally enrolled, of which 101 were diagnosed with GDM, and the other 298 were non-GDM. Moreover, GDM mouse model was generated with HFD-fed mice. The HFD-fed mice contained two groups, in which one was injected with recombinant protein mouse-derived RANKL and the other was injected equal volume of saline. Tropboblasts were used to investigate the mechanism of RANKL in maternal metabolism homeostasis. Results There was a negative correlation between serum RANKL level and the risk of GDM in both crude and adjusted models [OR = 0.993 (95%CI: 0.99–0.996), OR = 0.994 (95%CI: 0.99–0.997)]. Using restricted cubic spline plateau points to determine the optimal effect of serum RANKL. Threshold range is about 800–900 pg/mL. ROC analysis showed that serum RANKL had a high diagnostic value for GDM [AUC = 0.7024 (95% CI: 0.6520–0.7529), p < 0.0001, sensitivity = 0.842, specificity = 0.574]. Conclusions RANKL-treated HFD-fed mice exhibited improvements in glucose and insulin tolerance and serum insulin concentrations in animal model. Meanwhile, RANKL could promote glucose transported proteins ( Gluts ) mRNA expression. RANKL might be a diagnostic biomarker of GDM and as a potential drug target for GDM therapy via improving insulin sensitivity.

Source: Scientific Reports

DOI: 10.1038/s41598-026-71039-7

Authors: Wanxin Wu, Guiyuan Yu, Yuying Zhang, Binbin Huang, Fa Zeng

Institutions: Sun Yat-sen University, Anhui Medical University, Shenzhen Maternity and Child Healthcare Hospital

Language: English

Topic: Gestational Diabetes Research and Management

Subfield: Obstetrics and Gynecology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,690