[IP] How Slow Growth As A Fetus Can Cause Diabetes As An Adult
How Slow Growth As A Fetus Can Cause Diabetes As An Adult
ScienceDaily (May 8, 2008) - 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.
Journal reference: Development of type 2 diabetes following intrauterine
growth retardation in rats is associated with progressive epigenetic
silencing of Pdx1. Journal of Clinical Investigation. May 8, 2008.
Adapted from materials provided by <http://www.jci.org/> Journal of
Clinical Investigation, via <http://www.eurekalert.org/> EurekAlert!, a
service of AAAS.
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