Role of FoxO Proteins in Pancreatic .BETA. Cells

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  • KITAMURA Tadahiro
    Metabolic Signal Research Center, Institute for Molecular and Cellular Regulation, Gunma University
  • IDO KITAMURA Yukari
    Russ Berrie Diabetes Center, Department of Medicine, Columbia University

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Forkhead transcription factors of the FoxO family have important roles in cellular proliferation, apoptosis, differentiation and stress resistance. FoxO proteins also play important roles in metabolism of complex organisms. FoxO1 regulates glucose and lipid metabolism in liver, as well as preadipocyte, myoblast and vascular endothelial cell differentiation. In the hypothalamus, FoxO controls food intake. In this chapter, we review the role of FoxO in pancreatic β cells. Pancreatic β cells secrete insulin to maintain the plasma glucose levels in a strict physiological range. Defects of β cell function cause diabetes. The expression pattern of FoxO1 during pancreatic organogenesis is similar to that of Pdx1, Nkx2.2 and Pax4, transcription factors known to be critical for β cell development. FoxO1 is expressed in a subset of pancreatic duct cells, in which insulin and/or Pdx1 are occasionally expressed. FoxO1 inhibits β cell proliferation through suppression of Pdx1 by competing with FoxA2 and protects against β cell failure induced by oxidative stress through NeuroD and MafA induction. Thus, a series of FoxO1 studies in pancreas suggested that FoxO1 plays important roles in pancreatic β cell differentiation, neogenesis, proliferation and stress resistance. Genetic or pharmacological manipulation of FoxO can be used to prevent β cell failure or aid in the differentiation of uncommitted endocrine progenitors into β cells for transplantation.<br>

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  • Endocrine Journal

    Endocrine Journal 54 (4), 507-515, 2007

    一般社団法人 日本内分泌学会

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