Effect of PDE inhibitors on intracellular Ca²⁺ dynamics in INS-1 cells.

<p>A) Caffeine robustly elevates intracellular Ca²⁺ in INS-1 cells when added acutely; however, the subtype-selective PDE inhibitors and the pan PDE inhibitor IBMX have little effect. Data shown are the mean ± SE from representative experiments performed in quadruplicate. B) AUC analysis of Ca²⁺ dynamics stimulated with caffeine (5 mM), 8MM-IBMX (100 μM), cilostamide (1 μM), rolipram (10 μM) or IBMX (100 μM). Each experiment was normalized to the response elicited by caffeine. The Ca²⁺ response elicited by each of the subtype-selective PDE inhibitors as well as IBMX was significantly less than that of caffeine (****, P < 0.0001 compared to caffeine; One-way ANOVA, Tukey post-hoc test). Data shown are average ± SE from four independent experiments. C) Glucose (18 mM) elevates intracellular Ca²⁺ levels in INS-1 cells but the subtype-selective PDE inhibitors and the pan PDE inhibitor IBMX have no additional effect. Data shown are the mean ± SE from representative experiments performed in quadruplicate. D) AUC analysis of Ca²⁺ dynamics stimulated with glucose (18 mM) alone and in the presence of either 8MM-IBMX (100 μM), cilostamide (1 μM), rolipram (10 μM) or IBMX (100 μM). Each experiment was normalized to the response elicited by 18G. There was no significant difference among the treatment conditions. Data shown are average ± SE from four independent experiments.</p>