Leptin but not neuropeptide Y up-regulated glucagon-like peptide 1 receptor expression in GT1-7 cells and rat hypothalamic slices.
In an attempt to gain better insight into the central effects of glucagon-like peptide (GLP-1), we studied the action of glucose and of regulatory peptides on the expression of its receptor (GLP-1R) in hypothalamic GT1-7 cells and in ventromedial (VMH) and lateral (LH) rat hypothalamus slices. The promoter activity of GLP-1R in transfected GT1-7 cells increased with leptin, whereas neuropeptide Y (NPY) did not modify it. Interestingly, when cells were incubated with both NPY and leptin, NPY blocked the stimulating effect of leptin. The effects of leptin and NPY were also confirmed at messenger RNA levels. In hypothalamic slices, GLP-1R messenger RNA levels increased at higher glucose concentrations in the VMH. In addition, leptin exerted a stimulating effect; and NPY did not modify receptor expression. By contrast, in the LH, the opposite effects were found for those parameters, except at 20 mmol/L glucose. These findings suggest that the stimulating effect of leptin on GLP-1R expression, with no changes in NPY-induced activity, could enhance the anorexic actions generated through this receptor. In addition, the different responses of the VMH and LH may be related to specific functions of these structures, as already known in vivo, highlighting the interest of hypothalamic slices for this kind of study.
Sanz
Carmen
C
Department of Biochemistry and Molecular Biology, Faculty of Medicine, Complutense University, 28040 Madrid, Spain.
Vázquez
Patricia
P
Navas
M Angeles
MA
Alvarez
Elvira
E
Blázquez
Enrique
E
D000818:Animals; D000855:Anorexia / Q000503:physiopathology; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D000067757:Glucagon-Like Peptide-1 Receptor; D005947:Glucose / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D009924:Organ Culture Techniques; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D018027:Receptors, Glucagon / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D020738:Leptin; D009478:Neuropeptide Y; D012333:RNA, Messenger; D018027:Receptors, Glucagon; D005947:Glucose