Redox regulation of the insulin signalling pathway

Abstract

The peptide hormone insulin is a key regulator of energy metabolism, proliferation and survival. Binding of insulin to its receptor activates the PI3K/AKT signalling pathway, which mediates fundamental cellular responses. Oxidants, in particular H₂O₂, have been recognised as insulin-mimetics. Treatment of cells with insulin leads to increased intracellular H₂O₂ levels affecting the activity of downstream signalling components, thereby amplifying insulin-mediated signal transduction. Specific molecular targets of insulin-stimulated H₂O₂ include phosphatases and kinases, whose activity can be altered via redox modifications of critical cysteine residues. Over the past decades, several of these redox-sensitive cysteines have been identified and their impact on insulin signalling evaluated. The aim of this review is to summarise the current knowledge on the redox regulation of the insulin signalling pathway.

Keywords: Cysteine post-translational modification; FOXO; H(2)O(2); Insulin signalling; NRF2; ROS; Redox regulation; Type-2 diabetes.