Investigating a novel mechanism for improving beta-cell function in type 2 diabetes

Summary We aim to investigate whether pharmacological inhibition of Y1 receptor signalling will enhance β-cell function and improve glucose homeostasis in type 2 diabetes.

Project Details

Current efforts to enhance β-cell function focus mostly on the pathways that stimulate insulin release, very little is known about the inhibitory mechanisms that terminate insulin secretion. Improving β-cell function by inhibiting the counter-regulatory pathway that suppresses the release of insulin remains largely unexplored as a therapeutic option. Peptide YY has been shown to activate neuropeptide Y1 receptor to attenuate insulin secretion in mouse pancreatic islets. We have identified that the neuropeptide Y1 receptor is also expressed in the β-cells in humans. Our recent published studies (Loh et.al 2017 Nature Communications) have shown that pharmacological inhibition of this receptor using a Y1 receptor specific antagonist, BIBO3304, significantly enhanced β-cell function in human islets. Despite this, the beneficial effects of Y1 inhibition in improving β-cell function and glycemic control in type 2 diabetes remain to be examined. We will now extend our published work with a detailed exploration of Y1 receptor inhibition in type 2 diabetes models. We aim to investigate whether pharmacological inhibition of Y1 receptor signalling will enhance β-cell function and improve glucose homeostasis in type 2 diabetes.