IRF2BP2 attenuates gestational diabetes mellitus by activating AMPK signaling

Purpose: To investigate the role of interferon regulatory factor 2 binding protein 2 (IRF2BP2) in gestational diabetes mellitus (GDM). Methods: Mice were injected intraperitoneally with streptozotocin to establish a model of GDM and then subjected to intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test (IPITT) to determine glucose and insulin tolerances. Lipid metabolism was evaluated by enzyme-linked immunosorbent assay (ELISA). The histomorphology of pancreatic islets was assessed by hematoxylin and eosin staining. Results: IRF2BP2 was downregulated in pancreatic tissues of mice with GDM (p < 0.001). Mice in GDM group showed higher blood glucose levels than those in normal pregnancy group. However, overexpression of IRF2BP2 reduced glucose and insulin levels in mice with GDM. Overexpression of IRF2BP2 increased the level of high-density lipoprotein (HDL) and reduced triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL) levels in mice with GDM (p < 0.001). The histopathological changes in the islets of mice with GDM were also ameliorated by overexpression of IRF2BP2. Overexpression of IRF2BP2 reduced IL-6, IL-1 beta, and TNF-alpha levels and increased protein expression of p-AMPK in mice with GDM. Conclusion: IRF2BP2 ameliorates the outcomes of GDM and suppressed inflammation in mice with GDM through activation of AMPK signaling. Thus, IRF2BP2 is a potential therapeutic strategy for the management of GDM.