Insulin secretion: combined effects of phorbol ester and A23187.
The effect of the ionophore, A23187, and/or the phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), on insulin secretion were compared with those of glucose. Glucose induces a biphasic pattern of insulin secretion; A23187 a comparable initial spike but no second phase; and TPA a slowly progressive increase. Combined A23187 and TPA evoke a pattern similar to that induced by glucose. Forskolin enhances both phases of glucose- induced and of TPA-A23187-induced insulin secretion. These results are interpreted in terms of a model of cell activation in which two branches of the calcium messenger system, the calmodulin branch and the C-kinase branch, control, respectively, the initial and sustained phases of insulin secretion.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology*; D002147:Calmodulin / Q000378:metabolism; D004357:Drug Synergism; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010704:Phorbols / Q000494:pharmacology*; D011493:Protein Kinase C; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D002147:Calmodulin; D007328:Insulin; D010704:Phorbols; D000001:Calcimycin; D011494:Protein Kinases; D011493:Protein Kinase C; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate