EPAC2A ablation impairs dynamic insulin response to E4-mediated GSIS potentiation. A and B: In vivo studies. C–E: In vitro studies. A: Acute E4 administration prior to ipGTT reveals relatively improved glucose tolerance in WT as compared with EPAC2A KO mice.
B: Acute E4 administration prior to ipGTT elicits augmented GSIS in WT mice, while E4-stimulated GSIS augmentation is lacking
in EPAC2A KO counterparts. C: Perifusion studies show E4-stimulated GSIS augmentation in WT islets, which is muted in EPAC2A KO islets. D and E: Islet intracellular calcium dynamic changes detected with the Fura-2 method in EPAC2A KO and WT islets. D: Islets maintained in 3 mmol/L glucose show no differences in intracellular calcium levels. E: Increasing glucose levels from 5 to 10 mmol/L at time 0 min elicits an increase in intracellular calcium signal, which is
reduced in EPAC2A KO islets as compared with WT control islets. WT is represented in gray circles; EPAC2A KO is represented
in black circles. Results are shown as mean ± SEM of studies performed at least in triplicate. *P < 0.05.