Time-course of Ca2+-induced insulin secretion from perifused, electrically permeabilised islets of Langerhans: effects of cAMP and a phorbol ester.
The pattern of insulin secretion from electrically permeabilised islets was studied in a perifusion system. Increases in intracellular Ca2+ stimulated insulin secretion in a dose-related manner, but the secretory response to Ca2+ was only transient, with permeabilised islets becoming rapidly insensitive to a stimulatory concentration of Ca2+. Cyclic AMP and the protein kinase C activator, phorbol 12-myristate 13-acetate (PMA), both stimulated Ca2+-induced insulin secretion from perifused permeabilised islets by increasing the maximum secretory response to Ca2+, and by maintaining elevated rates of secretion when the permeabilised islets had become insensitive to the stimulatory effects of Ca2+. These results suggest that cAMP and PMA may act partly by modifying the magnitude of the secretory response to Ca2+, and also by Ca2+-independent effects on the secretory mechanism.
Jones
P M
PM
Biomedical Sciences Division, King's College London, Kensington, UK.
Persaud
S J
SJ
Howell
S L
SL
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D000242:Cyclic AMP / Q000494:pharmacology*; D004560:Electricity; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D051381:Rats; D012636:Secretory Rate / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors
D007328:Insulin; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium