FEBS Letters
Volume 582, Issue 1 , Pages 54-67, 9 January 2008

The FoxO transcription factors and metabolic regulation

Edited by Peter Tontonoz and Laszlo Nagy

21st Century COE Program for Signal Transduction Disease: Diabetes Mellitus as Model, Department of Clinical Molecular Medicine, Division of Diabetes, Digestive and Kidney Disease, Kobe University Graduate school of Medicine, Kobe 650-0017, Japan

Received 9 April 2007; accepted 6 November 2007. published online 16 November 2007.

Abstract 

Forkhead transcription factors FoxOs are conserved beyond species and regulated by insulin signaling pathway. FoxOs have diverse functions on differentiation, proliferation and cell survival. In calorie restriction (CR) or starvation, FoxOs are in nucleus, active transcriptionally, and increase hepatic glucose production, decrease insulin secretion, increase food intake and cause degradation of skeletal muscle for supplying substrates for glucose production. However, even in insulin resistance due to excessive calorie intake, FoxOs are active and causes type 2 diabetes and hyperlipidemia. The understanding of molecular mechanism how FoxOs affect glucose or lipid metabolism will shed light on the novel therapy of type 2 diabetes and the metabolic syndrome.

Keywords: FoxO, Metabolism, Phosphorylation, Transcription, Insulin resistance, Type 2 diabetes

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PII: S0014-5793(07)01169-6

doi:10.1016/j.febslet.2007.11.025

FEBS Letters
Volume 582, Issue 1 , Pages 54-67, 9 January 2008