Acute and chronic hyperglycemic effects of vasopressin in normal rats: involvement of V 1A receptors

Abstract : Recent epidemiological studies have revealed novel relationships between low water intake or high vasopressin (AVP) and the risk of hyperglycemia and diabetes. AVP V1A and V1B receptors (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.
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Soumis le : jeudi 21 mars 2019 - 13:31:44
Dernière modification le : vendredi 26 juillet 2019 - 11:22:08

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Christopher Taveau, Catherine Chollet, Daniel Bichet, Gilberto Velho, Gilles Guillon, et al.. Acute and chronic hyperglycemic effects of vasopressin in normal rats: involvement of V 1A receptors. AJP - Endocrinology and Metabolism, American Physiological Society, 2017, 312 (3), pp.E127-E135. ⟨10.1152/ajpendo.00269.2016⟩. ⟨hal-02075391⟩

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