FOXO1 (Onuma et al. 2006), which can function in collaboration with PPARGC1A (PGC-1alpha) (Puigserver et al. 2003), FOXO3 (Onuma et al. 2006), FOXO4 (Yang et al. 2002) and FOXO6 (Kim et al. 2011) directly stimulate transcription of the G6PC gene, encoding Glucose-6-phosphatase. G6PC generates glucose and enables maintenance of steady glucose blood levels during fasting. FOXO6 mRNA levels increase in liver cells during fasting (Kim et al. 2011). Upregulation of G6PC expression by FOXO1 and FOXO6 is inhibited by insulin. FOXO-mediated induction of G6PC is involved in excessive endogenous glucose production and fasting hyperglycemia in diabetes (Kim et al. 2011).