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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-32813

Riediger, T; Eisele, N; Scheel, C; Lutz, T A (2010). Effects of glucagon-like peptide 1 and oxyntomodulin on neuronal activity of ghrelin-sensitive neurons in the hypothalamic arcuate nucleus. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 298(4):R1061-R1067.

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Abstract

Glucagon-like peptide 1 (GLP-1) and oxyntomodulin (OXM) are structurally related gastrointestinal hormones that are secreted in response to food intake. They reduce food intake and body weight and exert partly overlapping actions on glucose homeostasis and gastrointestinal function. The hypothalamic arcuate nucleus (ARC) is among the central structures expressing a high density of GLP-1 receptors (GLP-1R), which are known to be activated by both peptides. It was the aim of our electrophysiological studies to characterize the effects of GLP-1 and OXM on functionally defined ghrelin-sensitive ARC neurons. GLP-1 and OXM (10(-7) M) exerted excitatory effects in about two thirds of ghrelin-inhibited neurons and in approximately one third of ghrelin-excited cells. In addition, a minor fraction of the ghrelin-excited cells was inhibited by both peptides. There was a high degree of co-sensitivity to GLP-1 and OXM and the effects of both hormones were blocked by the GLP-1 receptor (GLP-1R) antagonist exendin(9-39). The GLP-1R mediated excitations and inhibitions persisted under synaptic blockade indicating a direct postsynaptic mode of action. Our results demonstrate that GLP-1 and OXM directly and similarly alter neuronal activity in the ARC probably via a common GLP-1R mediated mechanism. Ghrelin-antagonistic effects on neuronal activity, which might be implicated in ghrelin-antagonistic in vivo actions resulting from GLP-1R stimulation (e.g. suppression of energy intake), predominated in ghrelin-inhibited ARC neurons. However, a subset of ghrelin-excited ARC neurons showed responses to OXM or GLP-1 suggesting the existence of a common mode of action for these hormones; the functional relevance of this effect remains to be elucidated. Key words: electrophysiology, glucagon-like peptide-1 receptor, exendin, hypothalamus.

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Institute of Veterinary Physiology
04 Faculty of Medicine > Center for Integrative Human Physiology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2010
Deposited On:15 Mar 2010 09:49
Last Modified:27 Nov 2013 19:38
Publisher:American Physiological Society
ISSN:0363-6119
Publisher DOI:10.1152/ajpregu.00438.2009
PubMed ID:20147608
Citations:Web of Science®. Times Cited: 7
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Scopus®. Citation Count: 7

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