Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5830124 | European Journal of Pharmacology | 2011 | 7 Pages |
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 - 30Â nmol/kg) reduced blood glucose levels dose-dependently by up to 49% during an intraperitoneal glucose tolerance test (PÂ <Â 0.001). The glucose-lowering effects were also observed after an intracerebroventricular (i.c.v.; 0.3 - 3Â 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% (PÂ <Â 0.01) and 46% (PÂ <Â 0.01), respectively. Exendin-4 (i.c.v.; 3Â nmol) also increased glucose-stimulated insulin secretion by 20% compared to controls (PÂ <Â 0.05). The GLP-1 receptor antagonist, exendin (9-39) (10Â nmol, i.c.v.) did not modify blood glucose levels but it antagonized the glucose-lowering effect of exendin-4 (1Â nmol, i.c.v.; PÂ <Â 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.