title: Chronic central neuropeptide Y infusion in normal rats: status of the hypothalamo-pituitary-adrenal axis, and vagal mediation of hyperinsulinaemia.
abstract: Neuropeptide Y in the hypothalamus is a potent physiological stimulator of feeding, and may contribute to the characteristic metabolic defects of obesity when hypothalamic levels remain chronically elevated. Since corticosterone and insulin are important regulators of fuel metabolism, the longitudinal effects of chronic (6 days) intracerebroventricular infusion of neuropeptide Y in normal rats on the hypothalamo-pituitary-adrenal axis and on insulin secretion were studied. Neuropeptide Y-infused rats were either allowed to eat ad libitum, or were pair-fed with normophagic control rats. Neuropeptide Y increased the basal plasma concentrations of adrenocorticotropic hormone and corticosterone during the first 2 days of its intracerebroventricular infusion and increased cold stress-induced plasma adrenocorticotropic hormone concentrations. After 4-6 days of central neuropeptide Y infusion, however, basal plasma adrenocorticotropic hormone and corticosterone concentrations were no different from control values (except in ad libitum-fed rats in which corticosteronaemia remained elevated), they were unaffected by the stress of cold exposure, and the hypothalamic content of corticotropin-releasing factor immunoreactivity was significantly decreased. A state of hyperinsulinaemia was present throughout the 6 days of intracerebroventricular neuropeptide Y infusion, being more marked in the ad libitum-fed than in the pair-fed group. The proportions of insulin, proinsulin, and conversion intermediates in plasma and pancreas were unchanged. Hyperinsulinaemia of the pair-fed neuropeptide Y-infused rats was accompanied by muscle insulin resistance and white adipose tissue insulin hyperresponsiveness, as assessed by the in vivo uptake of 2-deoxyglucose. Finally, bilateral subdiaphragmatic vagotomy prevented both the basal and the marked glucose-induced hyperinsulinaemia of animals chronically infused with neuropeptide Y, demonstrating that central neuropeptide Y-induced hyperinsulinaemia is mediated by the parasympathetic nervous system.
authors.affiliation: Laboratoire de Recherches Métaboliques, Faculty of Medicine, University of Geneva, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Sainsbury
authors.forename: F
authors.initials: F
authors.lastname: Rohner-Jeanrenaud
authors.forename: I
authors.initials: I
authors.lastname: Cusin
authors.forename: K E
authors.initials: KE
authors.lastname: Zakrzewska
authors.forename: P A
authors.initials: PA
authors.lastname: Halban
authors.forename: R C
authors.initials: RC
authors.lastname: Gaillard
authors.forename: B
authors.initials: B
authors.lastname: Jeanrenaud
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000032:analysis; D004435:Eating / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D007276:Injections, Intraventricular; D007328:Insulin / Q000097:blood; D018482:Muscle, Skeletal / Q000378:metabolism; D009478:Neuropeptide Y / Q000008:administration & dosage*; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000033:anatomy & histology; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology
chemical_list: D007328:Insulin; D009478:Neuropeptide Y; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D005947:Glucose; D003345:Corticosterone