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Description

Forkhead box O (FOXO) transcription factors play an important role in modulating metabolic functions and cell proliferation. Given the relatively high expression of FOXO1 in insulin-responsive tissues, this transcription factor is highly poised to regulate energy metabolism. When nutrient and insulin levels are low, FOXO1 promotes expression of gluconeogenic enzymes. Conversely, in the fed state, insulin levels rise and stimulate uptake of glucose primarily into skeletal muscle and other organs, including adipose tissue. Under certain pathophysiologic conditions, including insulin resistance, negative signaling to FOXO1 is compromised. Increased cell proliferation occurs when FOXO1 is inactivated when phosphorylated by Akt at Thr24.