Effect of 17[beta]-estradiol on insulin secretion and cytosolic calcium in Min6 mouse insulinoma cells and human islets of Langerhans

Al-Majed, H. T. and Squires, Paul E. and Persaud, S. J. and Huang, G.-C. C. and Amiel, S. and Whitehouse, B. J. and Jones, P. M. (2005) Effect of 17[beta]-estradiol on insulin secretion and cytosolic calcium in Min6 mouse insulinoma cells and human islets of Langerhans. Pancreas, 30 (4). pp. 307-313. ISSN 0885-3177

Full content URL: http://dx.doi.org/10.1097/01.mpa.0000161886.17492....

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Abstract

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-β-estradiol (17β-E2) 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 17β-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: 17β-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 μmol/L tolbutamide, 20 mmol/L KCl). Approximately 60% of MIN6 cells responded to 17β-E2 (1-100 nmol/L) with a small but sustained increase in Ca2+i, whereas 98% of MIN6 cells responded to tolbutamide (100 μmol/L). Similar effects were observed in experiments using human primary β cells. In contrast, 17β-E2 had no detectable effect on the increases in Ca2+i evoked by tolbutamide (100 μmol/L) or glucose (20 mmol/L). Conclusions: Our observations are consistent with a rapid effect of 17β-E2 to depolarize β cells leading to an influx of extracellular Ca2+ and the initiation of insulin secretion by the consequent elevations in Ca 2+i. We suggest that this may offer a mechanism through which circulating estradiol can influence β-cell responsiveness to other signals. Copyright © 2005 by Lippincott Williams & Wilkins.

Keywords:calcium ion, estradiol, fura 2, glucose, insulin, potassium chloride, tolbutamide, antidiabetic agent, calcium, animal cell, article, calcium cell level, cell membrane depolarization, controlled study, cytosol, extracellular calcium, human, human cell, in vitro study, insulin release, insulinoma, microfluorometry, mouse, nonhuman, pancreas islet, priority journal, animal, cytology, drug effect, metabolism, pancreas islet beta cell, physiology, secretion, signal transduction, tumor cell line, Animals, Calcium, Cell Line, Tumor, Humans, Hypoglycemic Agents, Insulin-Secreting Cells, Mice
Subjects:C Biological Sciences > C900 Others in Biological Sciences
Divisions:College of Science > School of Life Sciences
ID Code:14259
Deposited On:06 Jun 2014 08:53

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