Intrauterine growth retardation (IUGR), which results in a baby having a low weight at birth, has been linked to the development of type 2 diabetes in adulthood. It has been suggested that this is because the expression of key genes is altered during fetal development and that this affects disease susceptibility later in life. Evidence to support this hypothesis and indicating that the changes in gene expression might be permanent has now been provided by Rebecca Simmons and colleagues, at the University of Pennsylvania, Philadelphia, using a rat model of IUGR.
Pervious studies using the rat model of IUGR have shown decreased fetal expression of the gene Pdx1, which is critical for the development and function of the cells that become defective in type 2 diabetes (pancreatic beta-cells), and adult onset of diabetes. In this study, expression of Pdx1 was found to be reduced in pancreatic beta-cells throughout life following IUGR. The molecular mechanisms (known as epigenetic mechanisms because they affect gene expression without altering the information in the gene) that reduced Pdx1 expression in pancreatic beta-cells were found to change during development. One mechanism was observed in the fetus, one following birth, and one after the onset of diabetes in adulthood. Of interest, the mechanisms reducing Pdx1 gene expression in the fetus and following birth could be reversed, whereas those reducing Pdx1 gene expression in the adult were irreversible. These data provide new insight into the mechanisms by which diabetes develops in adulthood following IUGR.
TITLE: Development of type 2 diabetes following intrauterine growth retardation in rats is associated with progressive epigenetic silencing of Pdx1
Rebecca A. Simmons
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
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