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Both Epac1 and Epac2 are expressed in the pancreas (Leech et al., 2000), and under high glucose conditions, Ca 2+ flows into cells through VDC channels, and Epac2 opens RYR calcium channels in the endoplasmic reticulum, further increasing intracellular Ca 2+ concentrations and enhancing exocytosis of insulin-secreting vesicles (Holz, 2004