Glucose-stimulated somatostatin secretion by PKA or Epac2 activation. PKA- and Epac2-dependent pathways are involved in the regulation of somatostatin secretion. (A) Somatostatin secretion measured in islets exposed to 1 and 10 mM glucose under control condition or in the presence of 1 µM myristoylated PKI as indicated. (B) As in A, but the effect of Rp-8-Br-cAMPS (100 µM) was tested. (C) As in A, but the effect of 25 µM ESI-05 was tested. (D) As in A, but the effect of 100 nM GLP-1 on 10 mM glucose-stimulated somatostatin secretion in the presence or absence of Rp-8-Br-cAMPS (100 µM) was tested. In A–D, data are presented as mean values ± SEM for the indicated number of independent experiments (n). *, P < 0.05 and ***, P < 0.001 vs. 1 mM glucose with the same conditions; †, P < 0.05; ††, P < 0.01; and †††, P < 0.001 vs. 10 mM glucose alone (as indicated); ‡, P < 0.05 vs. 10 mM glucose in the presence of 100 nM GLP-1. [K+]o was 3.6 mM for all the experiments, and islets were from more than three animals for each experiment.