Oxytocin signal contributes to the adaptative growth of islets during gestation

Abstract

Background: Increased insulin production and secretion by pancreatic β-cells are important for ensuring the high insulin demand during gestation . However, the underlying mechanism of β-cell adaptation during gestation or gestational diabetes mellitus (GDM) remains unclear. Oxytocin is an important physio logical hormone in gestation and delivery, and it also contributes to the maintena nce of β-cell function. The aim of this study was to investigate the role of oxytocin i n β-cell adaptation during pregnancy. Methods: The relationship between the blood oxytocin level and pancreatic β-cell function in patients with GDM and healthy pregnant women was investigate d. Gestating and non-gestating mice were used to evaluate the in vivo effect of oxytocin signal on β-cells during pregnancy. In vitro experiments were performed on INS-1 insulinoma cells. Results: The blood oxytocin levels were lower in patients with GDM than in healthy pregnant women and were associated with impaired pancreatic β-cell function. Acute administration of oxytocin increased insulin secretion in both gestating and non-gestating mice. A 3-week oxytocin treatment promoted the prolif eration of pancreatic β-cells and increased the β-cell mass in gestating but not non-gestating mice. Antagonism of oxytocin receptors by atosiban impaired insulin secretion an d induced GDM in gestating but not non-gestating mice. Oxytocin enhanced glucose -stimulated insulin secretion, activated the mitogen-activated protein kinase pathway, and promoted cell proliferation in INS-1 cells. Conclusions: These findings provide strong evidence that oxytocin is needed for β-cell adaptation during pregnancy to maintain β-cell function, and the lack of oxytocin could be associated with the risk of GDM.

Keywords

• oxytocin
• gestational diabetes mellitus
• pancreatic β-cells
• insulin secretion
• proliferation