Insulin hypersensitivity in mice lacking the V1b vasopressin receptor |
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Authors: | Yoko Fujiwara Masami Hiroyama Atsushi Sanbe Toshinori Aoyagi Jun-ichi Birumachi Junji Yamauchi Gozoh Tsujimoto Akito Tanoue |
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Affiliation: | Department of Pharmacology, National Research Institute for Child Health and Development, Tokyo, Japan;Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University Faculty of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan |
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Abstract: | We have reported that [Arg8]-vasopressin-stimulated insulin release is blunted in islet cells isolated from V1b receptor-deficient ( V1bR −/−) mice. In this study, we used V1bR −/− mice to examine the physiological role of the V1b receptor in regulating blood glucose levels in vivo , and we found that the fasting plasma glucose, insulin and glucagon levels were lower in V1bR −/− mice than in wild-type ( V1bR +/+) mice. Next, we evaluated glucose tolerance by performing an intraperitoneal glucose tolerance test (GTT). The plasma glucose and insulin levels during the GTT were lower in V1bR −/− mice than in V1bR +/+ mice. An insulin tolerance test (ITT) revealed that, after insulin administration, plasma glucose levels were lower in V1bR −/− mice than in V1bR +/+ mice. In addition, a hyperinsulinaemic–euglycaemic clamp study showed that the glucose infusion rate was increased in V1bR −/− mice, indicating that insulin sensitivity was enhanced at the in vivo level in V1bR −/− mice. Furthermore, we found that the V1b receptor was expressed in white adipose tissue and that insulin-stimulated phosphorylation of Akt as an important signaling molecule was increased in adipocytes isolated from V1bR −/− mice. Thus, the blockade of the V1b receptor could result, at least in part, in enhanced insulin sensitivity by altering insulin signalling in adipocytes. |
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