Regulation of islet function and gene expression by prolactin during pregnancy

Abstract

Pancreatic islets adapt to insulin resistance of pregnancy by up regulating {beta}-cell proliferation and increase insulin secretion. Previously, we found that prolactin receptor (Prlr) signaling is important for this process, as heterozygous prolactin receptor-null (Prlr+/-) mice are glucose intolerant, had a lower number of {beta} cells and lower serum insulin levels than wild type mice during pregnancy. However, since Prlr expression is ubiquitous, to determine its {beta}-cell specific effects, we generated a transgenic mouse with a floxed Prlr allele under the control of an inducible promoter, allowing conditional deletion of Prlr from {beta} cells in adult mice. In this study, we found that {beta}-cell-specific Prlr reduction resulted in elevated blood glucose during pregnancy. Similar to our previous finding in mouse with global Prlr reduction, {beta}-cell-specific Prlr loss led to a lower {beta}-cell mass and a lower in vivo insulin level during pregnancy. However, these islets do not have an intrinsic insulin secretion defect when tested in vitro. Interestingly, when we compared the islet gene expression profile, using islets isolated from mice with global versus {beta}-cell-specific Prlr reduction, we found some important differences in genes that regulate apoptosis and insulin secretion. This suggests that Prlr has both cell-autonomous and non-cell-autonomous effect on {beta} cells, beyond its regulation of pro-proliferative genes.