Adaptation of Islets of Langerhans to Pregnancy: β-Cell Growth, Enhanced Insulin Secretion and the Role of Lactogenic Hormones

 

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Abstract

Pregnancy is a unique event in the life span of islet β-cells. Under the influence of pregnancy islet β-cells undergo major long term up-regulatory structural and functional changes in response to the increased demand for insulin. Adaptive changes that occur in islets during normal pregnancy include: 1) increased glucose-stimulated insulin secretion with a lowered threshold for glucosestimulated insulin secretion, 2) increased insulin synthesis, 3) increased β-cell proliferation and islet volume, 4) increased gap-junctional coupling among β-cells, 5) increased glucose metabolism, and 6) increased c-AMP metabolism. Of the islet changes that occur during pregnancy the increase in β-cell division and enhanced glucose sensitivity of insulin secretion are most notable. The increase in β-cell division leads to an increase in islet mass that contributes to the ability of islets to respond to the increased need for insulin. However, the increased glucose sensitivity of β-cells is likely to be more important. The lowering of the threshold for glucose stimulated insulin secretion is the primary mechanism by which β-cells can release significantly more insulin under normal blood glucose concentrations. Although the hormonal changes which occur during pregnancy are complex, it appears that lactogenic influences (either placental lactogen and/or prolactin) are sufficient to induce all of the up-regulatory changes that occur in islets during pregnancy. We have demonstrated that rat placental lactogens I and II are the hormones responsible for up-regulating islets during rodent pregnancy. Although most studies have been done using rodent islets, available evidence strongly suggests that human placental lactogen and/or human prolactin are the responsible lactogens for up-regulating islets during human pregnancy. A model for how lactogens up-regulate islets during pregnancy is proposed.