Calcium-induced insulin release in monolayer culture of the endocrine pancreas. Studies with ionophore A23187.
The role of Ca2+ on insulin release has been studied by the use of ionophore A23187. The ionophore complexes divalent cations and permits Ca2+ entry into cells by acting as a carrier in the plasma membranes. Cultured cells obtained by enzymatic digestion of pancreases from newborn rats were studied on the 3rd day of culture. With Ca2+ in the incubation medium the ionophore induced sustained insulin release even in the absence of glucose. Optimal effects of the ionophore were observed at 3 and 10 mug per ml in the presence of 0.3 to 1.0 mM Ca-2+. Under these conditions the insulin release was greater than that caused by 16.7 mM glucose. A graded response was observed to changes in Ca-2+ concentration from 0.1 to 1.0 mM Ca-2+. Higher Ca-2+ concentrations caused a large amount of insulin to be released promptly, but the release was not sustained. Mg-2+ and Sr-2+ were not found to substitute for Ca-2+. Ba-2+ at 0.3 mM stimulated insulin release even in the absence of ionophore. Cyclic adenosine 3':5'-monophosphate was able to increase ionophore-induced insulin release. The alpha-adrenergic effect of epinephrine to inhibit insulin release was not observed in the presence of Ca-2+ and the ionophore, and a stimulatory effect of epinephrine was seen. This unusual stimulatory effect of epinephrine was blocked by propranolol indicating a beta-adrenergic mechanism for epinephrine. It is concluded that Ca-2+, which plays an essential role in the stimulus-secretion coupling, can alone initiate and cause sustained insulin release.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000906:Antibodies; D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000494:pharmacology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D013324:Strontium / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D000906:Antibodies; D002264:Carboxylic Acids; D007328:Insulin; D001464:Barium; D011433:Propranolol; D000242:Cyclic AMP; D008274:Magnesium; D005947:Glucose; D002118:Calcium; D004837:Epinephrine; D013324:Strontium