A physiological role of glucagon-like peptide-1 receptors in the central nervous system of Suncus murinus (house musk shrew)
Author(s)
Author(s)
Lin, G.
Yew, D. T. W.
Rudd, J. A.
Date Issued
2011
Publisher
Elsevier
Journal
European Journal of Pharmacology
Volume
668
Issue
1–2
Start page
340
End page
346
Abstract
Glucagon-like peptide-1 (7–36) amide (GLP-1) is released from the gut as an incretin hormone to stimulate glucose-stimulated insulin secretion. GLP-1 is also produced in the central nervous system (CNS) as a neurotransmitter that regulates feeding behaviour. By using polyclonal antiserum against GLP-1 and GLP-1 receptors, we identified the distribution of GLP-1 immunoreactive fibres and GLP-1 receptor immunoreactivity in the ventromedial hypothalamus of Suncus murinus (house musk shrew). In functional studies, subcutaneous administration of exendin-4 (1 – 30 nmol/kg) reduced blood glucose levels dose-dependently by up to 49% during an intraperitoneal glucose tolerance test (P < 0.001). The glucose-lowering effects were also observed after an intracerebroventricular (i.c.v.; 0.3 – 3 nmol) or intracerebral ventromedial hypothalamic microinfusion (iVMH; 0.3 – 3 pmol) of exendin-4. The area under the curve values for glucose after i.c.v. and iVMH administrations of exendin-4 were reduced by up to 53% (P < 0.01) and 46% (P < 0.01), respectively. Exendin-4 (i.c.v.; 3 nmol) also increased glucose-stimulated insulin secretion by 20% compared to controls (P < 0.05). The GLP-1 receptor antagonist, exendin (9–39) (10 nmol, i.c.v.) did not modify blood glucose levels but it antagonized the glucose-lowering effect of exendin-4 (1 nmol, i.c.v.; P < 0.05). The data suggests that the central GLP-1 system may regulate glucose homeostasis by increasing insulin secretion. Further, GLP-1 receptors in the ventromedial hypothalamus appear to play an important role in the regulation of glucose homeostasis in S. murinus.
SFU Affiliated Publication
No
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