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

• Published in: Scientific reports Vol. 11; no. 1; p. 10372
• Main Authors: Shrivastava, Vipul, Lee, Megan, Lee, Daniel, Pretorius, Marle, Radford, Bethany, Makkar, Guneet, Huang, Carol
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 14.05.2021; Nature Publishing Group UK; Nature Portfolio
• Subjects: Adaptation; Apoptosis; Beta cells; Blood glucose; Gene expression; Hyperglycemia; Insulin; Insulin resistance; Insulin secretion; Pancreas; Pregnancy; Prolactin; Rodents; Secretion; Transgenic mice
• ISSN: 2045-2322; 2045-2322
• 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.