title: Effect of 17beta-estradiol on insulin secretion and cytosolic calcium in Min6 mouse insulinoma cells and human islets of Langerhans.
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-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.
authors.affiliation: Division of Reproductive Health, Endocrinology and Development, King's College London, London, United Kingdom.
authors.forename: Hana T
authors.initials: HT
authors.lastname: Al-Majed
authors.forename: Paul E
authors.initials: PE
authors.lastname: Squires
authors.forename: Shanta J
authors.initials: SJ
authors.lastname: Persaud
authors.forename: Guo-Cai C
authors.initials: GC
authors.lastname: Huang
authors.forename: Stephanie
authors.initials: S
authors.lastname: Amiel
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Whitehouse
authors.forename: Peter M
authors.initials: PM
authors.lastname: Jones
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D003600:Cytosol / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D007340:Insulinoma; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014044:Tolbutamide / Q000494:pharmacology
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D004958:Estradiol; D014044:Tolbutamide; D005947:Glucose; D002118:Calcium