title: Deleterious effects of supplementation with dehydroepiandrosterone sulphate or dexamethasone on rat insulin-secreting cells under in vitro culture condition.
abstract: Dehydroepiandrosterone (DHEA) and glucocorticoids are steroid hormones synthesised in the adrenal cortex. Administration of DHEA, its sulphate derivative, DHEAS, and more controversially dexamethasone (DEX), a synthetic glucocorticoid, have beneficial effects in diabetic animals. Cultivating BRIN-BD11 cells for 3 days with either DHEAS (30 muM) or DEX (100 nM), reduced total cell number and reduced cell viability and cellular insulin content. DHEAS-treated cells had poor glucose responsiveness and regulated insulin release, coupled with reduced basal insulin release. In contrast, DEX-treated cells lacked responsiveness to glucose and membrane depolarisation, and both protein kinase A (PKA) and protein kinase C (PKC) secretory pathways were desensitised. Therefore, we conclude that this steroid hormone and synthetic glucocorticoid are not beneficial to pancreatic beta-cells in vitro.
authors.affiliation: School of Biomedical Sciences, University of Ulster, BT52 1SA, Coleraine, N. Ireland, UK.
authors.forename: Hui-Kang
authors.initials: HK
authors.lastname: Liu
authors.forename: Brian D
authors.initials: BD
authors.lastname: Green
authors.forename: Neville H
authors.initials: NH
authors.lastname: McClenaghan
authors.forename: Jannie T
authors.initials: JT
authors.lastname: McCluskey
authors.forename: Peter R
authors.initials: PR
authors.lastname: Flatt
mesh_terms: D000818:Animals; D002452:Cell Count; D018929:Cell Culture Techniques; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019314:Dehydroepiandrosterone Sulfate / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects*; D051381:Rats; D013997:Time Factors
chemical_list: D007328:Insulin; D019314:Dehydroepiandrosterone Sulfate; D003907:Dexamethasone; D005947:Glucose