Endocrine Abstracts (2009) 20 S2.4

Incretin receptor signalling, [beta]-cell proliferation and survival

Daniel Drucker

Samuel Lunenfeld Research Institute, Mt Sinai Hospital, University of Toronto, Toronto, Canada.

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretin hormones secreted by gut endocrine cells that act on structurally related β-cell G protein coupled receptors to trigger glucose-dependent insulin secretion. Both peptide hormones augment glucose-stimulated insulin secretion although the actions of GIP are diminished in the setting of hyperglycemia. Moreover, the two incretin hormones, and their structurally related receptors, exert widely divergent biological actions on β-cell function following receptor agonist administration or genetic disruption of receptor signaling in vivo. Furthermore, there are significant differences in β-cell function and survival arising from pharmacological activation of incretin receptor signaling achieved using peptide agonists versus DPP-4 inhibition. The available data identify important differences in the endogenous physiological roles and pharmacological importance of murine GIP versus GLP-1 receptors versus DPP-4 inhibition for the preservation of β-cell mass and function in vivo.

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