Forskolin regulates HMGB1, independent of Epac1. REC were grown in normal glucose (5mM, NG), high glucose (25mM, HG), HG+forskolin (HG+Fors), or HG+forskolin+Epac1 siRNA (HG+Epac1 siRNA+Fors). Panel A shows PKA activity is increased by forskolin, and Panel B shows effective knockdown by Epac1 siRNA. Panel C shows IGFBP-3 levels, Panel D shows SIRT1 levels, Panel E shows cytoplasmic HMGB1 levels, and Panel F is nuclear HMGB1 levels. *P<0.05 vs. NG, #P<0.05 vs. HG. Data are mean ± SEM. N=4 for all groups.