Physiology of GLP-1--lessons from glucoincretin receptor knockout mice.
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.
Thorens
B
B
Department of Physiology, University of Lausanne, CH-1005 Lausanne, Switzerland. Bernard.Thorens@unil.ch
D000818:Animals; D001835:Body Weight / Q000502:physiology; D004435:Eating / Q000502:physiology; D005934:Glucagon / Q000502:physiology*; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D006339:Heart Rate / Q000502:physiology; D007515:Islets of Langerhans / Q000502:physiology*; D007858:Learning / Q000502:physiology; D008099:Liver / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000502:physiology*; D011498:Protein Precursors / Q000502:physiology*; D018027:Receptors, Glucagon / Q000172:deficiency / Q000502:physiology*
C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D010446:Peptide Fragments; D011498:Protein Precursors; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1; D005934:Glucagon