title: A physiological role of glucagon-like peptide-1 receptors in the central nervous system of Suncus murinus (house musk shrew).
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.
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China. stellacsw@cuhk.edu.hk
authors.forename: Sze Wa
authors.initials: SW
authors.lastname: Chan
authors.forename: Ge
authors.initials: G
authors.lastname: Lin
authors.forename: David Tai Wai
authors.initials: DT
authors.lastname: Yew
authors.forename: John Anthony
authors.initials: JA
authors.lastname: Rudd
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D000077270:Exenatide; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000737:chemistry / Q000378:metabolism; D000067757:Glucagon-Like Peptide-1 Receptor; D005947:Glucose / Q000494:pharmacology; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000187:drug effects; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology; D018027:Receptors, Glucagon / Q000378:metabolism*; D012788:Shrews; D014688:Venoms / Q000008:administration & dosage / Q000494:pharmacology; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
chemical_list: D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D010446:Peptide Fragments; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; C083773:exendin (9-39); D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; D005947:Glucose