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Acute and chronic hyperglycemic effects of vasopressin in normal rats : Involvement of V1A receptors

Taveau, Christopher; Chollet, Catherine; Bichet, Daniel G.; Velho, Gilberto; Guillon, Gilles; Corbani, Maithe; Roussel, Ronan; Bankir, Lise; Melander, Olle LU and Bouby, Nadine (2017) In American Journal of Physiology - Endocrinology and Metabolism 312(3). p.127-135
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 dosedependent increase in glycemia. Pretreatment with a selective V1AR antagonist, but not a V1BR antagonist, dose-dependently prevented the rise in glycemia. V1BR antagonism did... (More)

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 dosedependent 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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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Glucagon, Glycemia, Insulin, Vasopressin V receptor
in
American Journal of Physiology - Endocrinology and Metabolism
volume
312
issue
3
pages
127 - 135
publisher
American Physiological Society
external identifiers
  • scopus:85014540994
  • wos:000395805500001
ISSN
0193-1849
DOI
10.1152/ajpendo.00269.2016
language
English
LU publication?
yes
id
5c24183d-ca88-4973-b07c-e844e907c75d
date added to LUP
2017-03-24 14:31:54
date last changed
2018-01-07 11:56:56
@article{5c24183d-ca88-4973-b07c-e844e907c75d,
  abstract     = {<p>Recent epidemiological studies have revealed novel relationships between low water intake or high vasopressin (AVP) and the risk of hyperglycemia and diabetes. AVP V<sub>1A</sub> and V<sub>1B</sub> 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 V<sub>1A</sub>R and V<sub>1B</sub>R. We showed that acute injection of AVP induces a dosedependent increase in glycemia. Pretreatment with a selective V<sub>1A</sub>R antagonist, but not a V1BR antagonist, dose-dependently prevented the rise in glycemia. V<sub>1B</sub>R antagonism did not modify the hyperinsulinemic response, resulting from AVP-induced hyperglycemia, but enhanced the fall in glucagonemia. Acute administration of selective V<sub>1A</sub>R or V<sub>1B</sub>R agonists confirmed the involvement of V<sub>1A</sub>R 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 &lt; 0.01) without significant change in insulinemia. This effect was attenuated by cotreatment with a V<sub>1A</sub>R 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 V<sub>1A</sub>R activation and, thus, provide a pathophysiological explanation for the relationship observed in human cohorts between the AVP-hydration axis and the risk of diabetes.</p>},
  author       = {Taveau, Christopher and Chollet, Catherine and Bichet, Daniel G. and Velho, Gilberto and Guillon, Gilles and Corbani, Maithe and Roussel, Ronan and Bankir, Lise and Melander, Olle and Bouby, Nadine},
  issn         = {0193-1849},
  keyword      = {Glucagon,Glycemia,Insulin,Vasopressin V receptor},
  language     = {eng},
  number       = {3},
  pages        = {127--135},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology - Endocrinology and Metabolism},
  title        = {Acute and chronic hyperglycemic effects of vasopressin in normal rats : Involvement of V<sub>1A</sub> receptors},
  url          = {http://dx.doi.org/10.1152/ajpendo.00269.2016},
  volume       = {312},
  year         = {2017},
}