Beta cell adaptation to pregnancy requires prolactin action on both beta and non-beta cells

Sci Rep. 2021 May 14;11(1):10372. doi: 10.1038/s41598-021-89745-9.


Pancreatic islets adapt to insulin resistance of pregnancy by up regulating β-cell mass and increasing insulin secretion. Previously, using a transgenic mouse with global, heterozygous deletion of prolactin receptor (Prlr+/-), we found Prlr signaling is important for this adaptation. However, since Prlr is expressed in tissues outside of islets as well as within islets and prolactin signaling affects β-cell development, to understand β-cell-specific effect of prolactin signaling in pregnancy, we generated a transgenic mouse with an inducible conditional deletion of Prlr from β-cells. Here, we found that β-cell-specific Prlr reduction in adult mice led to elevated blood glucose, lowed β-cell mass and blunted in vivo glucose-stimulated insulin secretion during pregnancy. When we compared gene expression profile of islets from transgenic mice with global (Prlr+/-) versus β-cell-specific Prlr reduction (βPrlR+/-), we found 95 differentially expressed gene, most of them down regulated in the Prlr+/- mice in comparison to the βPrlR+/- mice, and many of these genes regulate apoptosis, synaptic vesicle function and neuronal development. Importantly, we found that islets from pregnant Prlr+/- mice are more vulnerable to glucolipotoxicity-induced apoptosis than islets from pregnant βPrlR+/- mice. These observations suggest that down regulation of prolactin action during pregnancy in non-β-cells secondarily and negatively affect β-cell gene expression, and increased β-cell susceptibility to external insults.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Blood Glucose / metabolism
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation
  • Humans
  • Insulin / metabolism
  • Insulin Resistance / genetics*
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology*
  • Mice
  • Mice, Knockout
  • Pregnancy
  • Pregnancy Complications / genetics
  • Pregnancy Complications / pathology*
  • Prolactin / metabolism*
  • Receptors, Prolactin / genetics
  • Receptors, Prolactin / metabolism*


  • Blood Glucose
  • Insulin
  • Receptors, Prolactin
  • Prolactin