Abstract
Arginine vasopressin (AVP) is well known for regulating fluid volume, osmotic balance, and vascular tone. Its role in the regulation of pancreatic α and β cell function has been reported, yet its effects are not fully understood, particularly regarding its interaction with plasma glucose levels. The osmotic and volume challenges posed by hyper- and hypoglycaemia in diabetes can be a significant complication of effective hormonal regulation of metabolism. In this study, we investigated the effects of AVP and synthetic peptide receptor agonists and antagonists on α and β cells in pancreatic tissue slices using live confocal Ca2+ imaging. Our findings demonstrate that AVP exerts glucose-dependent effects on both cell types. At low glucose concentrations, AVP, in combination with physiologically or pharmacologically increased cAMP levels, selectively activated α cells without significantly affecting β cells. In contrast, at higher glucose concentrations and pharmacologically elevated cAMP levels, physiological levels of AVP enhanced β cell activity, leading to increased Ca2+ oscillations and insulin release. In both cell types, AVP displayed a bell-shaped concentration dependence, with lower AVP concentrations stimulating hormone release and higher concentrations leading to diminished responses, consistent with inositol trisphosphate receptor (IP3R) activation and inactivation properties. Furthermore, our results indicate that AVP acts primarily through V1b receptors in β cells, with no involvement of V1a, V2 or oxytocin receptors. These findings provide new insights into the modulation of glucose-dependent release of pancreatic hormones by AVP in the context of changed blood osmolality due to hyper- or hypoglycemia in diabetes. Importantly, these results emphasize the potential of targeting AVP signaling pathways as a therapeutic approach in diabetes research, aiming to improve hormone regulation and nutrient homeostasis.
Competing Interest Statement
The authors have declared no competing interest.
