IL-34 causes inflammation and beta cell apoptosis and dysfunction in gestational diabetes mellitus

Abstract

Objective: Gestational diabetes mellitus (GDM) is characterized by glucos e intolerance during gestation. It is associated with a series of maternal an d foetal complications. Interleukin (IL)-34 is a recently discovered pro-inflammatory cy tokine that functions as a ligand for colony-stimulating factor-1 receptor (CSF-1R). The contribution of IL-34 in the development of multiple chronic inflammatory diseases and au toimmune diseases has been recently discovered. The aim of this study was to eval uate whether IL-34 participates in the pathogenesis of GDM. Method: A total of 120 women were enrolled in this study, which includ ed 60 GDM patients and age- and sex-matched healthy pregnant women. The e xpression of IL-34 in serum, cord blood and placental tissues was analysed by ELIS A and Western blot assays. The association between IL-34 levels and clinical featu res was also studied. We additionally evaluated the effect of recombinant mouse IL-34 (rm IL-34) on apoptosis and pancreatic β cell function. Results: We found that IL-34 expression is highly increased in serum, c ord blood and placental tissues in patients with GDM. In addition, there was a positive association between serum IL-34 and insulin resistance and glucose concentr ations. Our data also revealed that IL-34 contributes to the apoptosis of pancreatic β cells in GDM caused by CSF-1R. Furthermore, functional studies found that IL-34 inh ibited pancreatic β cell function and cell viability, while CSF-1R inhibitor blocked thi s effect. Conclusion: IL-34 plays a crucial role in the development of GDM by target ing CSF-1R, insulin production and β cell function.

Keywords

• gestational diabetes mellitus
• il-34
• csf-1r
• apoptosis
• pancreatic β cell