Effects of Ca2+ and a phorbol ester on insulin secretion from islets of Langerhans permeabilised by high-voltage discharge.
Isolated rat islets of Langerhans permeabilised by high-voltage discharge secreted insulin in response to elevations in Ca2+ over the range 100 nM to 10 microM Ca2+. The phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA), had no effects on insulin secretion in the absence of Ca2+. In the presence of Ca2+ concentrations of greater than 10 nM, TPA produced dose-related shifts in the Ca2+-activation curve to lower Ca2+ concentrations, together with marked increases in the maximum secretory response to Ca2+. These results suggest that, in islets, the activation of protein kinase C is important in modulating both the sensitivity of the exocytotic mechanism to intracellular Ca2+, and the magnitude of the insulin secretory response.
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D010539:Permeability; D010704:Phorbols / Q000494:pharmacology*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D007328:Insulin; D010704:Phorbols; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium