Arginine vasopressin and oxytocin effects in mouse pancreatic beta-cells. Receptors involved in stimulation of insulin release.
Recently AVP and OT were suggested to increase insulin release by stimulating phosphoinositide metabolism in pancreatic beta-cells. In this study, mouse islets were used to identify the receptors involved in the effects of AVP and OT. Both agents caused concentration-dependent (0.1 nM to 10 microM) increases in insulin release and IP levels. The potencies of AVP and OT were similar, and their maximal effects were not additive. Synthetic agonists selective for AVP (V1) and OT receptors in other tissues were equipotent with the natural agonists on insulin release and almost equipotent on IPs. Antagonists selective for V1 and OT receptors inhibited both types of effects with a potency that varied with the nature of the agonist. Both AVP and OT were approximately 10-fold potent on insulin release (EC50 approximately 2 nM) than on IPs (EC50 approximately 25 nM). Moreover, the antagonists more readily inhibited the effects of all agonists on IPs than on insulin release. Pancreatic beta-cells may possess either a single type of receptor that is distinct from classic V1 or OT receptors, but is closer to the latter, or both V1 and OT receptors coupled to common effectors. The acceleration of phosphoinositide turnover might not be the sole mechanism involved in the stimulation of insulin release by AVP and OT.
Gao
Z Y
ZY
Unit of Diabetes and Nutrition, University of Louvain, Faculty of Medicine, Brussels, Belgium.
Henquin
J C
JC
D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D010121:Oxytocin / Q000031:analogs & derivatives / Q000494:pharmacology*; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin / Q000187:drug effects* / Q000502:physiology
D007328:Insulin; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D010121:Oxytocin