Naringenin improves insulin sensitivity in gestational diabetes mellitus mice through AMPK

Background: Gestational diabetes mellitus (GDM) is a temporary form of diabetes during pregnancy, which influences the health of maternal-child in clinical practice. It is still urgent to develop new effective treatment for GDM. Naringenin is a bioactive ingredient with multiple activities including anti-diabetic. In current study, the effects of naringenin on GDM symptoms, insulin tolerance, inflammation, and productive outcomes were evaluated and the underlying mechanisms were explored. Methods: We administrated naringenin to GDM mice and monitored the GDM symptoms, glucose and insulin tolerance, inflammation and productive outcomes. We established tumor necrosis factor alpha (TNF-alpha)-induced insulin resistance skeletal muscle cell model and evaluated the effects of naringenin on reactive oxygen species (ROS) production, glucose uptake and glucose transporter type 4 (GLUT4) membrane translocation. Results: We found that naringenin ameliorated GDM symptoms, improved glucose and insulin tolerance, inhibited inflammation, and improved productive outcomes. It was further found that naringenin inhibited TNF-alpha-induced ROS production, enhanced GLUT4 membrane translocation, and glucose uptake, which were abolished by inhibition of AMP-activated protein kinase (AMPK). Conclusion: Naringenin improves insulin sensitivity in gestational diabetes mellitus mice in an AMPK-dependent manner.