Effects of Arginine Vasopressin on Islet Cells in Pancreatic Tissue Slices: Glucose-Dependent Modulation of IP ₃ Receptor-Specific Responses

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 Ca ²⁺ 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 Ca ²⁺ 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 (IP ₃ R) activation and inactivation properties. Furthermore, our results indicate that AVP acts primarily through V _1b receptors in β cells, with no involvement of V _1a , V ₂ 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.