AIMS: Glucocorticoids, such as dexamethasone, are widely used anti-inflammatory drugs. Their use is frequently associated with the development of steroid- associated diabetes. Pancreatic -cell dysfunction has been suggested to be one of the main causes of steroid-associated diabetes. However, the mechanism is not fully understood. Glycogen synthase kinase-3 (GSK-3) is a multifunctional serine/threonine kinase and plays an important role in energy metabolism, cell growth and apoptosis. Therefore, the contribution of GSK-3 in dexamethasone-induced pancreatic -cell apoptosis was determined in the present study. MAIN METHODS: The effect of dexamethasone treatment on rat pancreatic -cell line (INS-1) apoptosis (determined by TUNEL and Flow Cytometry), generation of reactive oxidative stress (ROS), and the phosphorylation status of GSK-3 was determined. The inhibitory effect of GSK-3 inhibitor-lithium chloride (LiCl) on dexamethasone-induced -cell apoptosis was also evaluated. KEY FINDINGS: Dexamethasone (0.1 M) treatment induced INS-1 apoptosis, which was associated with increased GSK-3 activation and increased NOX4-derived ROS generation. Pretreatment of INS-1 with LiCl inhibited dexamethasone induced ROS generation and INS-1 apoptosis. SIGNIFICANCE: This study provides a new mechanism of Dex induced pancreatic cell apoptosis and may serve as a new therapeutic option for treating GC induced diabetes.
