EPAC2A ablation impairs dynamic insulin response in model of β-cell autonomous GSIS augmentation (Δprkar1a mice). A–C: In vivo studies. D–F: In vitro studies. A: During ipGTT, Δprkar1a and Δprkar1a/EPAC2A KO mice exhibit similar glucose excursions. B: During ipGTT, Δprkar1a show, as compared with WT mice (Fig. 3), dramatically increased GSIS. Δprkar1a/EPAC2A KO mice exhibit reduced serum insulin levels as compared with Δprkar1a mice.
C: During ipITT, Δprkar1a/EPAC2A KO, as compared with Δprkar1a mice, show slightly increased insulin sensitivity, which does
not reach statistical significance. D: Perifusion studies of islets from Δprkar1a and Δprkar1a/EPAC2A KO mice. Δprkar1a islets exhibit a dramatically augmented
GSIS. In contrast, Δprkar1a/EPAC2A KO islets exhibit a relatively blunted first-phase GSIS, while second-phase GSIS is similar
in both groups. E and F: Islet Intracellular calcium dynamic changes detected with the Fura-2 method in Δprkar1a and Δprkar1a/EPAC2A KO islets. E: Islets maintained in 3 mmol/L glucose show no differences in intracellular calcium levels. F: Increasing glucose levels from 3 to 10 mmol/L at time 0 min elicits a dramatic increase in intracellular calcium signal
in Δprkar1a islets. Δprkar1a/EPAC2A KO islets show a blunted early (0–10 min) rise in glucose-stimulated intracellular calcium,
which, at later time points (10–20 min), is similar in both groups. Δprkar1a is represented in gray circles; Δprkar1a/EPAC2A
KO is represented in black circles. Results are shown as mean ± SEM of studies performed at least in triplicate. *P < 0.05.