Effect of 17β-estradiol on insulin secretion and cytosolic calcium in MIN6 mouse insulinoma cells and human islets of Langerhans

Objective: Female gonadal steroids can exert an insulinotropic effect in vivo. The objective of this study was to investigate the effects in vitro of 17-beta-estradiol (17 beta-E-2) on changes in cytosolic calcium ([Ca2+](i)) and on insulin secretion from the MIN6 mouse insulinoma cell line and human primary islets of Langerhans. Methods: Stimulus-induced changes in [Ca2+](i) were measured in Fura-2- loaded cells by single cell microfluorimetry. The effects of 17 beta-E2 on insulin secretion were measured in static incubation experiments, and the rate and pattern of secretory responses were studied in multi-channel perifusion experiments. Results: 17 beta-E-2 (1 - 100 nmol/L) enhanced basal (2 mmol/L glucose) insulin secretion but had no effect on secretory responses to 20 mmol/L glucose or to depolarizing stimuli ( 100 mmol/L tolbutamide, 20 mmol/L KCl). Approximately 60% of MIN6 cells responded to 17 beta-E-2 ( 1 - 100 nmol/L) with a small but sustained increase in [Ca2+](i), whereas 98% of MIN6 cells responded to tolbutamide ( 100 mu mol/L). Similar effects were observed in experiments using human primary beta cells. In contrast, 17 beta-E-2 had no detectable effect on the increases in [Ca2+](i) evoked by tolbutamide ( 100 mu mol/L) or glucose ( 20 mmol/L). Conclusions: Our observations are consistent with a rapid effect of 17 beta-E-2 to depolarize beta cells leading to an influx of extracellular Ca2+ and the initiation of insulin secretion by the consequent elevations in [Ca2+](i). We suggest that this may offer a mechanism through which circulating estradiol can influence beta-cell responsiveness to other signals.