Abstract
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, β-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 β-cells, although absence of both GLP-1 and GIP receptors leads to a more
severe phenotype characterized by a β-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.
Key words
GLP-1 receptor - GIP receptor - β-cells - Insulin secretion - Diabetes
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B. Thorens
Department of Physiology, University of Lausanne
27 rue du Bugnon · CH-1005 Lausanne · Switzerland
Telefon: +41 (21) 692 53 90
Fax: +41 (21) 692 53 55
eMail: Bernard.Thorens@unil.ch
