Effects of oxytocin on in vivo release of insulin and glucagon studied by microdialysis in the rat pancreas and autoradiographic evidence for [3H]oxytocin binding sites within the islets of Langerhans.
In the present investigation it was studied whether oxytocin administered directly in the pancreas of the rat stimulates the release of insulin and glucagon. In order to study such effects in vivo, a new experimental model applying the microdialysis technique was developed. To test the validity of the method, glucose or arginine were infused i.v. and it was shown that perfusate concentrations of insulin and glucagon increased significantly to 344 and 292% of basal overflow, respectively. Administration of oxytocin via the dialysis probe into the splenic portion of the pancreas resulted in significant elevations of insulin and glucagon concentrations to 210 (P less than 0.05) and 528% (P less than 0.01), respectively. The present study also includes a combined autoradiographic and immunohistochemical investigation of binding sites for oxytocin in the rat pancreas. A high density of [3H]oxytocin binding was present in the periphery of the islets of Langerhans, corresponding to the localization of the glucagon-producing alpha-cells. Both oxytocin and arginine(A)-vasopressin displaced [3H]oxytocin. The IC50 values were 10 and 180 nM, respectively. In conclusion, the oxytocin-induced release of insulin and glucagon as previously demonstrated in a number of species, may be due to a stimulation exerted by the peptide directly within the pancreas.
Stock
S
S
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
Fastbom
J
J
Björkstrand
E
E
Ungerstedt
U
U
Uvnäs-Moberg
K
K
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001345:Autoradiography; D001665:Binding Sites; D001667:Binding, Competitive; D003956:Dialysis; D005934:Glucagon / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D010121:Oxytocin / Q000378:metabolism / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D010121:Oxytocin; D005934:Glucagon; D001120:Arginine; D005947:Glucose