Prolactin Receptor Is Required for Normal Glucose Homeostasis and Modulation of β-Cell Mass during Pregnancy

TLDR: This is the first in vivo demonstration that the action of pregnancy hormones, acting through Prlr, is required for normal maternal glucose tolerance during pregnancy by increasing beta-cell mass.

Abstract: Increased islet mass is an adaptive mechanism that occurs to combat insulin resistance during pregnancy. Prolactin (PRL) can enhance β-cell proliferation and insulin secretion in vitro, yet whether it is PRL or other pregnancy-related factors that mediate these adaptive changes during pregnancy is unknown. The objective of this study was to determine whether prolactin receptor (Prlr) is required for normal maternal glucose homeostasis during pregnancy. An ip glucose tolerance test was performed on timed-pregnant Prlr+/+ and heterozygous null Prlr+/− mice on d 0, 15, and 18 of pregnancy. Compared with Prlr+/+ mice, Prlr+/− mice had impaired glucose clearance, decreased glucose-stimulated insulin release, higher nonfasted blood glucose, and lower insulin levels during but not before pregnancy. There was no difference in their insulin tolerance. Prlr+/+ mice show a significant incremental increase in islet density and β-cell number and mass throughout pregnancy, which was attenuated in the Prlr+/− mice. Prlr...