The Effect of Osmotically Stimulated Vasopressin on Glucose Regulation

Introduction The neurohypophysial hormone arginine vasopressin (AVP), also known as antidiuretic hormone, was one of the first hormone identified for its vasopressin properties in 1895 by Oliver and Schäfer. They showed that extract of pituitary gland increased blood pressure in anesthetized dogs. AVP is mainly synthesized in the paraventricular and supraoptic nucleus of the hypothalamus. The hormone is transferred to the neural lobe of the posterior pituitary where it is released to the circulation. Target organs perceive the hormonal stimuli by three different receptors: V1a, V1b and V2. The receptor V1a is mainly expressed in the vascular wall and is responsible for vasoconstriction. The receptor V1b is mainly found in the anterior pituitary, mediating the secretion of the adrenal corticotropin hormone, while the V2 receptor is mainly expressed in nephron tubules triggering water reabsorption. Since the discovery of AVP, both the vasopressin and antidiuretic properties have been very well studied and documented.

Other than the AVP effects on blood pressure and water homeostasis, the hormone is implicated in a variety of other functions including pain, bone and lipid metabolism, hypertension, social behavior, aging, cognitive function, cellular proliferation, inflammation, infections, homeostasis, hypothalamic-pituitary-adrenal axis, and diabetes. All these effects could provide useful insight into many diseases. Therefore, the focus of this application is on the effects of AVP on glucose regulation in healthy humans.

AVP is known to enhance hepatic glycogenolysis by activation of V1a receptors and by increasing the release of glucagon, resulting in increased glucose levels in experimental animals. Even when glucagon receptors in the liver are blocked, AVP still increases blood glucose. The V1b receptors have been identified in both alpha and beta cells of the islets of Langerhans. Thus, AVP stimulates insulin secretion counteracting the increase in blood glucose. In an experiment with AVP V1a and V1b receptor knockout mice, alterations in glucose and fat metabolism were observed, suggesting that AVP might play a role in glucose regulation and metabolic disorders. Studies in humans with a genetic variation of AVP V1a receptor showed increased prevalence of diabetes in overweight or subjects with high fat diet. Recently, a study in rats prone to metabolic dysfunction, examined the effect of long-term influence of vasopressin on glucose homeostasis. It reported that high vasopressin enhanced hyperinsulemia and glucose intolerance in obese rats, while treatment with vasopressin receptor V1a antagonist reduced glucose intolerance.

In a French epidemiological study, a cohort of 3,615 males and females with normal fasting blood glucose was followed for 9 years. It indicated that water intake was inversely and independently associated with the risk of developing hyperglycemia. The authors hypothesized that their results were due to hypohydration related increase in plasma vasopressin. More recently, a Swedish cohort of 2,064 subjects from the malmo diet and cancer study was analyzed after 15.8 y with an oral glucose tolerance test. They found that copeptin (a reliable and clinical surrogate marker of AVP) independently predicted diabetes mellitus and abdominal adiposity.

Interestingly, hypohydration and low water drinking is linked to chronic elevated AVP. In a recent study with free-living adults, low habitual water intake led to significantly elevated AVP compared to adults with high water intake.