Normal pregnancy is associated with increased insulin resistance as a metabolic adaptation to
the nutritional demands of the placenta and fetus, and this is amplified in obese mothers. Insulin resistance
is normally compensated for by an adaptive increase in pancreatic β-cell mass together with enhanced
glucose-stimulated insulin release. Placentally-derived hormones and growth factors are central
to the altered pancreatic morphology and function. A failure of β-cells to undergo adaptive change after
the first trimester has been linked with gestational diabetes. In the pregnant mouse, an increase in β-cell
replication contributes to a 2-3-fold increase in mass peaking in late gestation, depending on the proliferation
of existing β-cells, the differentiation of resident progenitor β-cells, or islet cell transdifferentiation.
Using mouse models and human studies placenta- and islet of Langerhans-derived molecules
have been identified that are likely to contribute to the metabolic adaptations to pregnancy and
whose physiology is altered in the obese, glucose-intolerant mother. Maternal obesity during pregnancy
can create a pro-inflammatory environment that can disrupt the response of the β-cells to the endocrine
signals of pregnancy and limit the adaptive changes in β-cell mass and function, resulting in an increased
risk of gestational diabetes.
Keywords: β-cell, pancreas, placenta, placental lactogen, proliferation, apelin, kisspeptin, gestational diabetes.
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