FIGURE 5.

cAMP-Epac stimulates Oct-1 nuclear exclusion in pancreatic and intestinal endocrine cells. A–C, forskolin/IBMX (F/I, 10 μm each) reduced the nuclear content of Oct-1 in InR1-G9 (A) and STC-1 (B), but not in Caco-2 (C). WCL, whole cell lysate; NE, nuclear extract. Reduced nuclear Oct-1 content was associated with increased Cdx-2 expression (A and B). D–F, PKA-active STC-1 cells (D and E) or PKA-deficient InR1-G9 cells (F) were treated with the indicated chemicals for 2 h. 8-pMeOPT-2′-O-Me-cAMP, defined as ESCA (20 μm); H89 is a PKA inhibitor (10 μm); and PD98059 is an MEK inhibitor (50 μm). Nuclear extracts were assessed by Western blotting. G and H, STC-1 (G) and InR1-G9 (H) cell lines were treated with forskolin/IBMX (10 μm each) for the indicated time before harvesting. Whole cell lysates were utilized in assessing total and phosphorylated ERK and CREB.