Ontology of the apelinergic system in mouse pancreas during pregnancy and relationship with β-cell mass

The apelin receptor (Aplnr) and its ligands, Apelin and Apela, contribute to metabolic control. The insulin resistance associated with pregnancy is accommodated by an expansion of pancreatic beta -cell mass (BCM) and increased insulin secretion, involving the proliferation of insulin-expressing, glucose transporter 2-low (Ins(+)Glut2(LO)) progenitor cells. We examined changes in the apelinergic system during normal mouse pregnancy and in pregnancies complicated by glucose intolerance with reduced BCM. Expression of Aplnr, Apelin and Apela was quantified in Ins(+)Glut2(LO) cells isolated from mouse pancreata and found to be significantly higher than in mature beta -cells by DNA microarray and qPCR. Apelin was localized to most beta -cells by immunohistochemistry although Aplnr was predominantly associated with Ins(+)Glut2(LO) cells. Aplnr-staining cells increased three- to four-fold during pregnancy being maximal at gestational days (GD) 9-12 but were significantly reduced in glucose intolerant mice. Apelin-13 increased beta -cell proliferation in isolated mouse islets and INS1E cells, but not glucose-stimulated insulin secretion. Glucose intolerant pregnant mice had significantly elevated serum Apelin levels at GD 9 associated with an increased presence of placental IL-6. Placental expression of the apelinergic axis remained unaltered, however. Results show that the apelinergic system is highly expressed in pancreatic beta -cell progenitors and may contribute to beta -cell proliferation in pregnancy.

Automated summary

The study found that insulin resistance during pregnancy can be regulated by increasing the proliferation of pancreatic beta-cell mass. The apelin receptor and its ligands are expressed at significantly higher levels in pancreatic beta-cell progenitors than in mature cells, with Apelin playing a crucial role in beta-cell proliferation. Elevated serum Apelin levels in glucose intolerant pregnant mice may be associated with an increase in placental IL-6.