Deleterious effects of supplementation with dehydroepiandrosterone sulphate or dexamethasone on rat insulin-secreting cells under in vitro culture condition.
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.
Liu
Hui-Kang
HK
School of Biomedical Sciences, University of Ulster, BT52 1SA, Coleraine, N. Ireland, UK.
Green
Brian D
BD
McClenaghan
Neville H
NH
McCluskey
Jannie T
JT
Flatt
Peter R
PR
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
D007328:Insulin; D019314:Dehydroepiandrosterone Sulfate; D003907:Dexamethasone; D005947:Glucose