a, Ad-CRE-luc activity (top) and CRTC2 protein amounts (bottom) in mice fasted for 6 or 24 hours. Intra-peritoneal glucagon injection indicated. b, and c, Effect of 6 or 18 hour fasting on Ad-G6Pase-luc activity (b), G6Pase mRNA amounts (c), and blood glucose concentrations (c) in mice infected with Ad-CRTC2i, Ad-FOXO1i, or (USi) control virus (n=4, (*) P< .05; (**) P< .02; (***) P< .01). d, Top, activities of wild-type or mutant Ad-G6Pase-luc reporters defective in CREB (CREmut) or FOXO1 (IREmut) binding. Mice were fasted for 6 or 18 hours as indicated (n=4, *;P<.05). Bottom, chromatin immunoprecipitation (ChIP) assay showing binding of myc-tagged FOXO1 or Flag-epitope tagged CRTC2 to the G6Pase promoter in HepG2 hepatocytes exposed to FSK for 6 or 18 hours. For panels b, c, d, data are means ± s.e.m.