Insulin hypersensitivity in mice lacking the V1b vasopressin receptor

Abstract

We have reported that [Arg 8 ]-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.

The stimuli-specific role of vasopressin in the hypothalamus–pituitary–adrenal axis response to stress

“…The weaker stimulus, LPS injection, induced ACTH elevation only in di/C rats, resembling previous studies using V1b receptor KO mice (Lolait et al 2007a) and V1b receptor antagonist During insulin-induced hypoglycaemia a preferential release of AVP over CRH into the hypophysial portal blood was described (Plotsky et al 1985). The role of AVP was further confirmed in V1b receptor KO mice not only on blood glucose regulation (Fujiwara et al 2007), but also directly on the HPA axis (Fujiwara et al 2007, Lolait et al 2007a. Our results suggest a prominent, although not exclusive, role for AVP in the regulation of ACTH secretion during insulininduced hypoglycaemia.…”

Sex differences in the association between plasma copeptin and incident type 2 diabetes: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study

“…AVP stimulates glycogenolysis and gluconeogenesis through the arginine vasopressin receptor 1 A (V1a) receptors in the liver [7]. In addition, AVP has been shown to induce glucagon and insulin release from the pancreas, mediated by V1b receptors on islet cells [10]. Furthermore, AVP, via the same receptor (V1b), exerts stimulatory effects in maintaining basal secretion of ACTH and corticosterone, and in modulating hypothalamic-pituitary-adrenal axis (HPA) activity under stress conditions [9].…”

“…The link between the AVP stress-adaptation system and type 2 diabetes may lie in stimulatory effects of AVP on hepatic glucose production [7], effects on insulin release from the pancreas [8], stimulation of endogenous cortisol secretion [9] and adverse effects on whole-body insulin resistance [10]. Of note, there are marked differences in responsiveness of the AVP stress-adaptation system between men and women [11,12].…”

First and third trimester serum concentrations of adropin and copeptin in gestational diabetes mellitus and normal pregnancy

“…In the population-based study conducted in Sweden, copeptin was an independent predicting factor for diabetes mellitus [21]. In an animal study, elevated AVP level as a result of AVP resistance at the level of V1aR was related to insulin resistance and diabetes mellitus [22,23]. However, a recent study of Yeung and coauthors (2014) investigates serum copeptin levels during pregnancy in relation to multiple pregnancy complications risk.…”