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 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 proliferation of existing β-cells, the differentiation of resident progenitor β-cells, or islet cell trans-differentiation. 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: pancreas, placenta, placental lactogen, proliferation, apelin, kisspeptin, gestational diabetes
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