Research ArticleCell Biology

Spatial Control of Epac2 Activity by cAMP and Ca2+-Mediated Activation of Ras in Pancreatic β Cells

Science Signaling  30 Apr 2013:
Vol. 6, Issue 273, pp. ra29
DOI: 10.1126/scisignal.2003932

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Sugar-Induced Oscillations

Glucose stimulation of pancreatic β cells triggers increases in the concentrations of adenosine 3′,5′-monophosphate (cAMP) and Ca2+, which activate various signaling pathways that culminate in pulses of insulin release. The guanine nucleotide exchange factor Epac2 promotes insulin secretion through various mechanisms, including activation of the small guanosine triphosphatase Rap1. Idevall-Hagren et al. performed imaging and biochemical analyses in a pancreatic β cell line and β cells in isolated islets and found that glucose stimulation resulted in translocation of Epac2 from the cytosol to the plasma membrane. This translocation occurred in a cyclical, oscillatory manner that corresponded to and required oscillations in the concentrations of cAMP, which directly activates Epac2, and in Ca2+, which indirectly activates Ras, a protein that recruits Epac2 to the plasma membrane. Activation of Rap1 at the plasma membrane also occurred in an oscillatory manner. Thus, the pulsatile release of insulin from pancreatic β cells involves oscillating signals that include oscillations in the plasma membrane localization of Epac2.