Evaluating glucose-dependent insulinotropic polypeptide and glucagon as key regulators of insulin secretion in the pancreatic islet

The incretin axis is an essential component of postprandial insulin secretion and glucose homeostasis. There are two incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which exert multiple actions throughout the body. A key cellular target for the incretins are pancreatic beta-cells, where they potentiate nutrient-stimulated insulin secretion. This feature of incretins has made this system an attractive target for therapeutic interventions aimed at controlling glycemia. Here, we discuss the role of GIP in both beta-cells and alpha-cells within the islet, to stimulate insulin and glucagon secretion, respectively. Moreover, we discuss how glucagon secretion from alpha-cells has important insulinotropic actions in beta-cells through an axis termed alpha- to beta-cell communication. These recent advances have elevated the potential of GIP and glucagon as a therapeutic targets, coinciding with emerging compounds that pharmacologically leverage the actions of these two peptides in the context of diabetes and obesity.