Vasopressin and hydration play a major role in the development of glucose intolerance and hepatic steatosis in obese rats

Abstract

Aims/hypothesis High plasma copeptin, a marker of vasopressin (VP) secretion, has been shown to be associated with the metabolic syndrome and development of type 2 diabetes in humans. The present study was designed to determine the long-term influence of plasma VP concentration in a rodent model prone to metabolic dysfunction. Methods Obese Zucker rats and their lean counterparts were submitted for 4 weeks to one of three protocols inducing different levels of VP. Circulating VP was either reduced by increasing the daily water intake (low-VP), or increased by a chronic i.p. infusion of VP (high-VP). The control rats had normal VP levels that depended on their own regulation of water intake and VP secretion.Results Compared with controls with normal VP, lean rats with high-VP had a higher fasting glycaemia after 4 weeks. In obese rats, high-VP promoted hyperinsulinaemia, glucose intolerance, assessed by glucose and insulin tolerance tests, and an impaired response to a pyruvate challenge. Conversely, treatment with a selective arginine vasopressin receptor 1A (V1aR) antagonist reduced glucose intolerance. Low-VP obese rats had unchanged glucose tolerance but exhibited a drastic decrease in liver steatosis compared with control obese rats, associated with low hepatic triacylglycerol and cholesterol content, and reduced expression of hepatic lipogenic genes. These effects were independent of changes in body adiposity, and plasma sodium and osmolality did not differ among groups.Electronic supplementary material The online version of this article

Effects of hydration on plasma copeptin, glycemia and gluco-regulatory hormones: a water intervention in humans

“…Given the multiple reports on an independent relationship between high copeptin and risk of cardiometabolic diseases, the potential of using increased hydration as a preventive tool for these diseases has acquired increasing interest. Importantly, in animal models, beneficial effects on metabolism have been demonstrated through VP reduction achieved by increased hydration, whereas elevation of VP deteriorated glucose tolerance, pointing at a likely causal relationship [20]. Furthermore, genetic variation in the human VP gene was recently associated with both elevated copeptin and increased risk of hyperglycemia, providing additional support of causality between elevated copeptin and metabolic disease [35].…”

Antagonism of vasopressin V2 receptor improves albuminuria at the early stage of diabetic nephropathy in a mouse model of type 2 diabetes

“…Thus, we cannot rule out that the phenotype observed in treated db/db mice was, at least in part, indirectly related to an activation of renal, vascular and hepatic V1aR (Cantau et al, 1984;Morita et al, 2001;Taveau et al, 2015). However, lack of increase in blood pressure or glycaemia during V2R antagonist treatment is not in favor of a strong V1aR stimulation.…”

Higher plain water intake is associated with lower type 2 diabetes risk: a cross-sectional study in humans

“…The link between arginine vasopressin, hydration status and glucose intolerance has recently been demonstrated in rats; elevated arginine vasopressin levels led to higher fasting glycemia in lean rats and hyperinsulinemia and glucose intolerance in obese rats [27]. Additionally, low arginine vasopressin was induced by increasing some rats' plain water intake.…”