Suppression of the Nuclear Factor Eny2 Increases Insulin Secretion in Poorly Functioning INS-1E Insulinoma Cells
Figure 5
Exendin-4 signaling downstream of cAMP, via PKA and EPAC. (a) Insulin secretion from INS-1E cells treated with 50 nmol/l exendin-4 with and without the PKA inhibitor H-89. Exendin-4 induced insulin secretion from Eny2-knockdown cells was reduced by 80% with PKA inhibition. (b, c) Insulin secretion after stimulation with forskolin, the EPAC-specific activator 8-CPT-Me-cAMP, and the PKA-specific activator N6-Bnz-cAMP; ((b) absolute values; (c) secreted insulin relative to 16.7 mmol/l glucose alone). PKA-specific activation was enhanced in Eny2 knockdown cells, both in absolute insulin values and relative to 16.7 mM glucose alone. The EPAC activator 8-CPT-Me-cAMP was active in cells after Eny2 suppression but not in control cells. This effect was not statistically significant with respect to absolute insulin values but in relative terms (c). *, **, ***; one-way ANOVA with posttests and unpaired -test.
