Figure 10.

Schematic of pathways for transcriptional activation of Forkhead box protein O1 (FOXO1) and IGF-1 in the mouse liver. (A) FOXO1 activates its own transcription, which leads to activation of genes such as glucose-6-phosphatase (G6pase), phosphoenolpyruvate kinase (Pepck), and insulinlike growth factor binding protein 1 (Igfbp1). (B) In the livers of Agpat1^−/− mice, decreased expression of Foxo1 resulted in decreased expression of Foxo1, G6Pase, Pepck, and Igfbp1. (C) The GH signaling pathway, which results in the phosphorylation of Stat5b, is shown. Upon dimerization, phosphorylated Stat5b moves into the nucleus and activates transcription of Igf-1. The Igf-1 promoter also contains FOXO1 binding sites, which could also activate Igf-1; however, this has not been shown experimentally. (D) In the livers of Agpat1^−/− mice, the GH signaling pathway remains intact. However, a decrease in Igf-1 expression, which could result from the decreased Foxo1 levels, is shown. This event is not related to the phosphorylation of FOXO1. The thick downward arrows on far right represent decreased transcription, whereas the thick upward arrows represent increased transcription.