Effects of Ca2+ and a phorbol ester on insulin secretion from islets of langerhans permeabilised by high‐voltage discharge

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Abstract
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 μM 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 > 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.