title: Acute and chronic hyperglycemic effects of vasopressin in normal rats: involvement of V1Areceptors.
abstract: Recent epidemiological studies have revealed novel relationships between low water intake or high vasopressin (AVP) and the risk of hyperglycemia and diabetes. AVP V1Aand V1Breceptors (R) are expressed in the liver and pancreatic islets, respectively. The present study was designed to determine the impact of different levels of circulating AVP on glucose homeostasis in normal Sprague-Dawley rats, as well as the respective roles of V1AR and V1BR. We showed that acute injection of AVP induces a dose-dependent increase in glycemia. Pretreatment with a selective V1AR antagonist, but not a V1BR antagonist, dose-dependently prevented the rise in glycemia. V1BR antagonism did not modify the hyperinsulinemic response, resulting from AVP-induced hyperglycemia, but enhanced the fall in glucagonemia. Acute administration of selective V1AR or V1BR agonists confirmed the involvement of V1AR in the hyperglycemic effect of AVP. In chronic experiments, AVP levels were altered in both directions. Sustained AVP infusion through implantable minipumps induced a time-dependent increase in fasting glycemia, whereas lowering endogenous AVP by increasing water intake had no effect. After 4 wk of AVP infusion, the rise in glycemia amounted to 1.1 mmol/l (P< 0.01) without significant change in insulinemia. This effect was attenuated by cotreatment with a V1AR antagonist. Similar results were observed in lean Zucker rats. These findings demonstrate for the first time a causal link between chronic high AVP and hyperglycemia through V1AR activation and, thus, provide a pathophysiological explanation for the relationship observed in human cohorts between the AVP-hydration axis and the risk of diabetes.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers, Paris, France.|Université Pierre et Marie Curie, Paris, France.|Université Paris Descartes, Paris, France.
authors.forename: Christopher
authors.initials: C
authors.lastname: Taveau
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers, Paris, France.|Université Pierre et Marie Curie, Paris, France.|Université Paris Descartes, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Chollet
authors.affiliation: Department of Physiology and Medicine, Sacré-Coeur Hospital, Montreal, Canada.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Bichet
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers, Paris, France.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Velho
authors.affiliation: INSERM U1191, Institut de Génomique Fonctionnelle, Montpellier, France.|Centre Nationnal de la Recherche Scientifique, UMR 5203, Montpellier France.|Université de Montpellier, Montpellier, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Guillon
authors.affiliation: INSERM U1191, Institut de Génomique Fonctionnelle, Montpellier, France.|Centre Nationnal de la Recherche Scientifique, UMR 5203, Montpellier France.|Université de Montpellier, Montpellier, France.
authors.forename: Maithe
authors.initials: M
authors.lastname: Corbani
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers, Paris, France.|Université Paris Diderot, Paris, France.|Department of Diabetology-Endocrinology-Nutrition, Departement Hospitalo Universitaire Fibrosis, Inflammation and Remodeling, Bichat Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Ronan
authors.initials: R
authors.lastname: Roussel
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers, Paris, France.|Université Pierre et Marie Curie, Paris, France.|Université Paris Descartes, Paris, France.
authors.forename: Lise
authors.identifier: 0000-0002-3321-0819
authors.initials: L
authors.lastname: Bankir
authors.affiliation: Department of Clinical Sciences, Malmö, Lund University, Malmö, Sweden; and.|Department of Internal Medicine, Malmö, Skåne University Hospital, Malmö, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers, Paris, France; nadine.bouby@crc.jussieu.fr.|Université Pierre et Marie Curie, Paris, France.|Université Paris Descartes, Paris, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Bouby
mesh_terms: D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D055879:Gene Knock-In Techniques; D005934:Glucagon / Q000097:blood / Q000187:drug effects*; D006943:Hyperglycemia / Q000097:blood*; D006946:Hyperinsulinism / Q000097:blood; D007211:Indoles / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D008297:Male; D061848:Optical Imaging; D010179:Pancreas / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D017483:Receptors, Vasopressin / Q000819:agonists / Q000187:drug effects* / Q000378:metabolism
chemical_list: C456029:1-(5-chloro-1-((2,4-dimethoxyphenyl)sulfonyl)-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl)-4-hydroxy-N,N-dimethyl-2-pyrrolidinecarboxamide; D065092:Antidiuretic Hormone Receptor Antagonists; D001786:Blood Glucose; C000591332:FE 201874; D007211:Indoles; D007328:Insulin; D010456:Peptides, Cyclic; D011759:Pyrrolidines; D017483:Receptors, Vasopressin; C582098:V1a vasopressin receptor, rat; D001127:Arginine Vasopressin; D005934:Glucagon; C082134:relcovaptan
keywords: glucagon; glycemia; insulin; vasopressin V1A receptor; vasopressin V1B receptor