Physiology of GLP-1--lessons from glucoincretin receptor knockout mice

Horm Metab Res. Nov-Dec 2004;36(11-12):766-70. doi: 10.1055/s-2004-826161.


GLP-1 has both peripheral and central actions, as this hormone is secreted by gut endocrine cells and brainstem neurons projecting into the hypothalamus and other brain regions. GLP-1 has multiple regulatory functions participating in the control of glucose homeostasis, beta-cell proliferation and differentiation, food intake, heart rate and even learning. GLP-1 action depends on binding to a specific G-coupled receptor linked to activation of the adenylyl cyclase pathway. Analysis of mice with inactivation of the GLP-1 receptor gene has provided evidence that absence of GLP-1 action in the mouse, despite this hormone potent physiological effects when administered in vivo, only leads to mild abnormalities in glucose homeostasis without any change in body weight. However, a critical role for this hormone and its receptor was demonstrated in the function of the hepatoportal vein glucose sensor, in contrast to that of the pancreatic beta-cells, although absence of both GLP-1 and GIP receptors leads to a more severe phenotype characterized by a beta-cell-autonomous defect in glucose-stimulated insulin secretion. Together, the studies of these glucoincretin receptor knockout mice provide evidence that these hormones are part of complex regulatory systems where multiple redundant signals are involved.

Publication types

  • Review

MeSH terms

  • Animals
  • Body Weight / physiology
  • Eating / physiology
  • Glucagon / physiology*
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptide-1 Receptor
  • Heart Rate / physiology
  • Islets of Langerhans / physiology*
  • Learning / physiology
  • Liver / metabolism
  • Mice
  • Mice, Knockout
  • Peptide Fragments / physiology*
  • Protein Precursors / physiology*
  • Receptors, Glucagon / deficiency
  • Receptors, Glucagon / physiology*


  • Glp1r protein, mouse
  • Glucagon-Like Peptide-1 Receptor
  • Peptide Fragments
  • Protein Precursors
  • Receptors, Glucagon
  • Glucagon-Like Peptide 1
  • Glucagon