Activation of promoter activity of the catalytic subunit of γ-glutamylcysteine ligase (GCL) in brain endothelial cells by insulin requires antioxidant response element 4 and altered glycemic status: Implication for GCL expression and GSH synthesis

► Insulin activates GCL promoter under increased or decreased glucose conditions. ► Glycemic requirement was abrogated by insulin-hydroperoxide co-administration. ► Intact antioxidant response element-4 was critical for GCL promoter activation. ► Only at low glucose did promoter activation correlate with GCL and GSH increases. ► Neither ROS nor metabolic stress is key player in promoter activation at low glucose.