Identifying adipocyte-derived peptides that regulate islet function: implications for diabetes therapy

Around 400 million people worldwide currently have type 2 diabetes (T2D), in which peripheral cells show reduced sensitivity to insulin and islet beta-cells do not secrete sufficient insulin to maintain low blood glucose levels. Several pharmacotherapies for T2D are available, but they all have side-effects associated with their use and there is a need to identify safe, effective drugs that maintain beta-cell mass and improve insulin secretory function. We have identified that islets express nearly 300 G-protein-coupled receptors (GPCRs), but only one of them (GLP-1 receptor) is targeted for treating T2D. There is also evidence that peptides secreted from insulin target tissues, such as adipocytes, can act at beta-cells to regulate their function. This PhD project will identify GPCR-activating peptides that are secreted from adipocytes under insulin-sensitive and insulin-resistant conditions, and provide data underpinning the development of adipocyte-derived GPCR ligands as novel therapeutics to increase beta-cell functional mass.