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Eur J Pharmacol. 2009 Jun 24;613(1-3):182-8. doi: 10.1016/j.ejphar.2009.04.008. Epub 2009 Apr 16.

Both V(1A) and V(1B) vasopressin receptors deficiency result in impaired glucose tolerance.

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1
Department of Pharmacology, National Research Institute for Child Health and Development, Tokyo, Japan.

Abstract

[Arg(8)]-vasopressin (AVP) is involved in the regulation of glucose homeostasis via vasopressin V(1A) and vasopressin V(1B) receptor. Our previous studies have demonstrated that vasopressin V(1A) receptor deficient (V(1A)R(-/-)) mice exhibited hyperglycemia, vasopressin V(1B) receptor deficient (V(1B)R(-/-)) mice, in contrast, exhibited hypoglycemia with hypoinsulinemia. These findings indicate that vasopressin V(1A) receptor deficiency results in decreased insulin sensitivity, whereas vasopressin V(1B) receptor deficiency results in increased insulin sensitivity. In our previous and present studies, we used the glucose tolerance test to investigate glucose tolerance in mutant mice, lacking either the vasopressin V(1A) receptor, the vasopressin V(1B) receptor, or both receptors, that were kept on a high-fat diet. Glucose and insulin levels were lower in V(1B)R(-/-) mice than in wild type (WT) mice when both groups were fed the high-fat diet, which indicates that the insulin sensitivity of the V(1B)R(-/-) mice was enhanced. V(1A)R(-/-) mice on the high-fat diet, on the other hand, exhibited overt obesity, along with an impaired glucose tolerance, while WT mice on the high-fat diet did not. Next, in order to assess the effect of vasopressin V(1B) receptor deficiency on the development of glucose intolerance caused by vasopressin V(1A) receptor deficiency, we generated mice that were deficient for both vasopressin V(1A) receptor and vasopressin V(1B) receptor (V(1AB)R(-/-)), fed them a high-fat diet, and examined their glucose tolerances using the glucose tolerance test. Glucose tolerance was impaired in V(1AB)R(-/-) mice, suggesting that the effects of vasopressin V(1B) receptor deficiency could not influence the development of hyperglycemia promoted by vasopressin V(1A) receptor deficiency, and that blockade of both receptors could lead to impaired glucose tolerance.

PMID:
19375419
DOI:
10.1016/j.ejphar.2009.04.008
[Indexed for MEDLINE]
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