Pancreatic β-Cell Response to Increased Metabolic Demand and to Pharmacologic Secretagogues Requires EPAC2A

(Downloading may take up to 30 seconds. If the slide opens in your browser, select File -> Save As to save it.)

Click on image to view larger version.

FIG. 4.
FIG. 4.

EPAC2A ablation impairs dynamic insulin response in diet-induced obesity and insulin resistance model. AC: In vivo studies. DF: In vitro studies. A: HFD-fed WT mice show impaired ip glucose tolerance, which is more pronounced in HFD-fed EPAC2A KO mice. B: HFD-fed WT mice show augmented serum insulin excursions in response to ip glucose. In comparison, EPAC2A KO mice show a delayed and impaired insulin response to ip glucose. C: HFD-fed EPAC2A KO mice, as compared with WT controls, show slightly increased insulin sensitivity, which does not compensate their impaired glucose tolerance (A). D: Perifusion studies of islets from HFD-fed mice show GSIS augmentation in WT islets, which is blunted in EPAC2A KO islets mainly in the early phases (40–45 min) after glucose stimulus to the islets. E and F: Islet intracellular calcium dynamic changes detected with the Fura-2 method in EPAC2A KO and WT islets of HFD-fed mice. 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 an increase in intracellular calcium signal. 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 WT and EPAC2A KO 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.

This Article

  1. Diabetes vol. 62 no. 8 2796-2807