Direct modulation of pancreatic CCK receptors and enzyme secretion by insulin in isolated pancreatic acini from diabetic rats.
The effect of insulin on pancreatic enzyme secretion was studied in vitro by using isolated pancreatic acini prepared from rats rendered diabetic with streptozotocin. Preincubation of acini with insulin increased the maximal release of amylase and ribonuclease in response to CCK8 but not to carbamylcholine, a secretagogue acting via a different receptor. Insulin by itself had no effect on enzyme release. The effect of insulin was time dependent and increased up to 2 h, the longest time studied. An effect was observed at 1 nM insulin and the maximal effect was observed at 100 nM. The properties of CCK receptors on the acini were studied using biologically active 125I-BH-CCK33. Insulin pretreatment decreased both the affinity of the high-affinity CCK receptors and the capacity of the low-affinity CCK receptors. Within the framework of the current model, in which occupancy of high-affinity CCK receptors stimulates and low-affinity receptors inhibits amylase release, the change in receptors induced by insulin could account for the altered enzyme secretion. Thus, insulin appears to have a direct effect to regulate CCK receptors and CCK-induced secretion in isolated pancreatic acini.
D000681:Amylases / Q000378:metabolism; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002766:Cholecystokinin / Q000378:metabolism / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011949:Receptors, Cholecystokinin; D012844:Sincalide; D013997:Time Factors
D007328:Insulin; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D011949:Receptors, Cholecystokinin; D002217:Carbachol; D002766:Cholecystokinin; D000681:Amylases; D012844:Sincalide