Differences in Intracellular Calcium Oscillations in Response to Glucose in Pancreatic Islets of Pregnant and Non‐pregnant Mice

Abstract

During pregnancy, the female body needs to adapt the energy homeostasis to accommodate the needs of a growing fetus. Therefore, the insulin resistance of the mother increases. This process is counterbalanced by increased insulin secretion from pancreatic β-cells. In rodents, both β-cell proliferation and increased glucose stimulated insulin secretion contribute to this compensation. To study basic mechanisms underlying this increased insulin secretion, we compare the intracellular Ca2+ oscillations in pancreatic islets isolated from pregnant and from non-pregnant mice. Islets were isolated on gestational day 16 from pregnant wildtype C57BL/6N mice and from non-pregnant control mice, aged 12-15 weeks. Calcium imaging studies using fluorescence microscopy were performed in the presence of different glucose concentrations. Pancreatic islets clearly showed a pregnancy phenotype characterized by different responses to glucose, and their size seemed to be increased during pregnancy. In islets isolated from pregnant mice, a larger proportion of the islets respond to a lower glucose concentration (6-6.5 mM) by initiating Ca2+ oscillations. Islets from pregnant mice react with a different oscillation pattern compared to those from non-pregnant mice. When 6.5 mM glucose was applied for 30 minutes, the oscillation frequency was increased compared to the oscillation pattern in islets from non-pregnant mice. No significant difference in the lag time between the application of the glucose and the occurrence of the first calcium spike was found. The general calcium levels in the islets from pregnant mice were elevated compared to those of non-pregnant mice. Remarkably, the opposite relation was observed when the glucose stimulus was increased to 8 mM glucose. In this condition, non-pregnant islets oscillate significantly faster compared to pregnant islets but the oscillations from islets of pregnant mice are wider. These results suggest that islets of pregnant mice are more sensitive to glucose in terms of Ca2+ signaling.