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 (17beta-E2) on changes in cytosolic calcium ([Ca]i) and on insulin secretion from the MIN6 mouse insulinoma cell line and human primary islets of Langerhans.
Methods: Stimulus-induced changes in [Ca]i were measured in Fura-2-loaded cells by single cell microfluorimetry. The effects of 17beta-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: 17Beta-E2 (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 micromol/L tolbutamide, 20 mmol/L KCl). Approximately 60% of MIN6 cells responded to 17beta-E2 (1-100 nmol/L) with a small but sustained increase in [Ca]i, whereas 98% of MIN6 cells responded to tolbutamide (100 micromol/L). Similar effects were observed in experiments using human primary beta cells. In contrast, 17beta-E2 had no detectable effect on the increases in [Ca]i evoked by tolbutamide (100 micromol/L) or glucose (20 mmol/L).
Conclusions: Our observations are consistent with a rapid effect of 17beta-E2 to depolarize beta cells leading to an influx of extracellular Ca and the initiation of insulin secretion by the consequent elevations in [Ca]i. We suggest that this may offer a mechanism through which circulating estradiol can influence beta-cell responsiveness to other signals.