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

Am J Physiol Endocrinol Metab. 2024 Jul 1;327(1):E103-E110. doi: 10.1152/ajpendo.00360.2023. Epub 2024 May 22.

Abstract

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 β-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 β-cells and α-cells within the islet, to stimulate insulin and glucagon secretion, respectively. Moreover, we discuss how glucagon secretion from α-cells has important insulinotropic actions in β-cells through an axis termed α- to β-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.

Keywords: GIP; glucagon; islet; α-cell; β-cell.

Publication types

  • Review

MeSH terms

  • Animals
  • Gastric Inhibitory Polypeptide* / metabolism
  • Glucagon* / metabolism
  • Glucagon-Like Peptide 1 / metabolism
  • Glucagon-Secreting Cells / metabolism
  • Humans
  • Incretins / metabolism
  • Insulin / metabolism
  • Insulin Secretion* / physiology
  • Insulin-Secreting Cells / metabolism
  • Islets of Langerhans* / drug effects
  • Islets of Langerhans* / metabolism

Substances

  • Gastric Inhibitory Polypeptide
  • Glucagon
  • Glucagon-Like Peptide 1
  • Incretins
  • Insulin