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. Author manuscript; available in PMC: 2015 Jan 30.

Published in final edited form as: Cell Metab. 2010 Jun 9;11(6):543–553. doi: 10.1016/j.cmet.2010.04.007

Involvement of Epac2 in α-cell exocytosis and glucagon secretion.

(A) Changes in membrane capacitance (ΔC_m) elicited by voltage-clamp depolarization from −70 mV to −10 mV under control conditions (Ctrl), in the presence of 0.1 mM of the Epac2 agonist 8CPT-2Me-cAMP (8-CPT) and in the simultaneous presence of 8CPT-2Me-cAMP and 2 μM isradipine (Isr + 8-CPT).

(B) Changes in membrane capacitance (ΔC_m) displayed against membrane potential of depolarization (V) under control conditions (■), after inclusion of 0.1 mM 8CPT-2Me-cAMP in the intracellular medium (○), and in 8CPT-2Me-cAMP containing cells exposed to 2 μM isradipine (). Data are mean values ± S.E.M. of 7-13 experiments. *p<0.05, **p<0.01 and ***p<0.001 for comparisons between 8CPT-2Me-cAMP alone or 8CPT-2Me-cAMP in the simultaneous presence of isradipine vs. control. ††p<0.01 for values in simultaneous presence of 8CPT-2Me-cAMP and isradipine vs. 8CPT-2Me-cAMP alone.

(C) Whole-cell Ca²⁺-currents recorded under control conditions (Ctrl), after intracellular application of 100 μM 8-CPT-2Me-cAMP (8-CPT) and in the presence of 8-CPT and 2 μM isradipine.

(D) Peak Ca²⁺-currents recorded under control conditions (■), after intracellular addition of 8-CPT (○) and after intracellular application of 8-CPT when L-type Ca²⁺-channels were blocked by isradipine (2 μM). *p<0.05 and **p<0.01 for the stimulatory effects of 8-CPT (vs. Ctrl) and †p<0.05 and ††p<0.01 for the effect of isradipine (vs. 8-CPT). (n=5-10 experiments in each group)

(E) Glucagon secretion from wildtype mouse islets under control conditions (Ctrl; 1 mM glucose), in the presence of 100 nM GLP-1 or 5 μM adrenaline (Adr) in the absence and presence of 10 μM 8-Br-Rp-cAMPS. n=6-8. **p<0.01 and ***p<0.001 vs. Ctrl in the absence or presence of 8-Br-Rp-cAMPS; ††p<0.01 and †††p<0.001 vs. corresponding value in the absence of 8-Br-Rp-cAMPS. Glucose was present at 1 mM.

(F) As in C using islets from Epac2 null mice. n=5-8. **p<0.01 and ***p<0.001 vs. Ctrl in the absence or presence of 8-Br-Rp-cAMPS. ††p<0.05 vs. corresponding value in the absence of 8-Br-Rp-cAMPS.

Inline graphic — Involvement of Epac2 in α-cell exocytosis and glucagon secretion.

(A) Changes in membrane capacitance (ΔC_m) elicited by voltage-clamp depolarization from −70 mV to −10 mV under control conditions (Ctrl), in the presence of 0.1 mM of the Epac2 agonist 8CPT-2Me-cAMP (8-CPT) and in the simultaneous presence of 8CPT-2Me-cAMP and 2 μM isradipine (Isr + 8-CPT).

(B) Changes in membrane capacitance (ΔC_m) displayed against membrane potential of depolarization (V) under control conditions (■), after inclusion of 0.1 mM 8CPT-2Me-cAMP in the intracellular medium (○), and in 8CPT-2Me-cAMP containing cells exposed to 2 μM isradipine (). Data are mean values ± S.E.M. of 7-13 experiments. *p<0.05, **p<0.01 and ***p<0.001 for comparisons between 8CPT-2Me-cAMP alone or 8CPT-2Me-cAMP in the simultaneous presence of isradipine vs. control. ††p<0.01 for values in simultaneous presence of 8CPT-2Me-cAMP and isradipine vs. 8CPT-2Me-cAMP alone.

(C) Whole-cell Ca²⁺-currents recorded under control conditions (Ctrl), after intracellular application of 100 μM 8-CPT-2Me-cAMP (8-CPT) and in the presence of 8-CPT and 2 μM isradipine.

(D) Peak Ca²⁺-currents recorded under control conditions (■), after intracellular addition of 8-CPT (○) and after intracellular application of 8-CPT when L-type Ca²⁺-channels were blocked by isradipine (2 μM). *p<0.05 and **p<0.01 for the stimulatory effects of 8-CPT (vs. Ctrl) and †p<0.05 and ††p<0.01 for the effect of isradipine (vs. 8-CPT). (n=5-10 experiments in each group)

(E) Glucagon secretion from wildtype mouse islets under control conditions (Ctrl; 1 mM glucose), in the presence of 100 nM GLP-1 or 5 μM adrenaline (Adr) in the absence and presence of 10 μM 8-Br-Rp-cAMPS. n=6-8. **p<0.01 and ***p<0.001 vs. Ctrl in the absence or presence of 8-Br-Rp-cAMPS; ††p<0.01 and †††p<0.001 vs. corresponding value in the absence of 8-Br-Rp-cAMPS. Glucose was present at 1 mM.

(F) As in C using islets from Epac2 null mice. n=5-8. **p<0.01 and ***p<0.001 vs. Ctrl in the absence or presence of 8-Br-Rp-cAMPS. ††p<0.05 vs. corresponding value in the absence of 8-Br-Rp-cAMPS.