Journal article
Dehydroepiandrosterone inhibits intracellular calcium release in beta-cells by a plasma membrane-dependent mechanism
Steroids, Vol.71(8), pp.691-699
08/01/2006
DOI: 10.1016/j.steroids.2006.04.001
PMID: 16725167
Abstract
Both dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) affect glucose stimulated insulin secretion, though their cellular mechanisms of action are not well characterized. We tested the hypothesis that human physiological concentrations of DHEA alter insulin secretion by an action initiated at the plasma membrane of beta-cells. DHEA alone had no effect on intracellular calcium concentration ([Ca2+](i)) in a rat beta-cell line (INS-1). However, it caused an immediate and dose-dependent inhibition of carbachol-induced Ca2+ release from intracellular stores, with a 25% inhibition at zero. One nanometer DHEA. DHEA also inhibited the Ca2+ mobilizing effect of bombesin (29% decrease), but did not inhibit the influx of extracellular Ca2+ evoked by glyburide (100 mu M) or glucose (15 mM). The steroids (androstenedione, 17-alpha-hydroxypregnenolone, and DHEAS) had no inhibitory effect on carbachol-induced intracellular Ca2+ release. The action of DHEA depended on a signal initiated at the plasma membrane, since membrane impermeant DHEA-BSA complexes also inhibited the carbachol effect on [Ca2+](i) (39% decrease). The inhibition of carbachol-induced Ca2+ release by DHEA was blocked by pertussis toxin (PTX). DHEA also inhibited the carbachol induction of phosphoinositide generation, with a maximal inhibition at 0.1 nM DHEA. Furthermore, DHEA inhibited insulin secretion induced by carbachol in INS-1 cells by 25%, and in human pancreatic islets by 53%. Taken together, this is the first report showing that human physiological concentrations of DHEA decrease agonist-induced Ca2+ release by a rapid, non-genomic mechanism in INS-1 cells. Furthermore, these data provide evidence consistent with the existence of a specific plasma membrane DHEA receptor, mediating this signal transduction pathway by pertussis toxin-sensitive G-proteins. (c) 2006 Elsevier Inc. All rights reserved.
Details
- Title: Subtitle
- Dehydroepiandrosterone inhibits intracellular calcium release in beta-cells by a plasma membrane-dependent mechanism
- Creators
- Dongmin Liu - Roy J. and Lucille A. Carver College of MedicineMin Ren - Roy J. and Lucille A. Carver College of MedicineXinyu Bing - Roy J. and Lucille A. Carver College of MedicineCorey Stotts - Roy J. and Lucille A. Carver College of MedicineSundeep Deorah - Roy J. and Lucille A. Carver College of MedicineLaurie Love-Homan - Roy J. and Lucille A. Carver College of MedicineJoseph S. Dillon - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- Steroids, Vol.71(8), pp.691-699
- Publisher
- Elsevier
- DOI
- 10.1016/j.steroids.2006.04.001
- PMID
- 16725167
- ISSN
- 0039-128X
- eISSN
- 1878-5867
- Number of pages
- 9
- Grant note
- DK20579; DK25295 / NIDDK NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) AG55741; R01 AG018928 / NIA NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) R01AG018928 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) P60DK020579 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
- Language
- English
- Date published
- 08/01/2006
- Academic Unit
- Critical Care; Stead Family Department of Pediatrics; Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984360043902771
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