Type 1 11beta -hydroxysteroid dehydrogenase mediates glucocorticoid activation and insulin release in pancreatic islets.
Metabolic transformation of glucocorticoid hormones constitutes a determinant of their cell-specific effects. The most important reaction for this class of steroids is the reversible C11 keto/beta-hydroxyl conversion between receptor-binding 11beta-OH steroids and the nonbinding 11-oxo compounds, ca...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2000
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| _version_ | 1797079931034796032 |
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| author | Davani, B Khan, A Hult, M Mårtensson, E Okret, S Efendic, S Jörnvall, H Oppermann, U |
| author_facet | Davani, B Khan, A Hult, M Mårtensson, E Okret, S Efendic, S Jörnvall, H Oppermann, U |
| author_sort | Davani, B |
| collection | OXFORD |
| description | Metabolic transformation of glucocorticoid hormones constitutes a determinant of their cell-specific effects. The most important reaction for this class of steroids is the reversible C11 keto/beta-hydroxyl conversion between receptor-binding 11beta-OH steroids and the nonbinding 11-oxo compounds, carried out by 11beta-hydroxysteroid dehydrogenases (11beta-HSDs). In this study, we determined the role of glucocorticoid conversion by 11beta-HSD in pancreatic islets and its function in the regulation of insulin release. Pancreatic islets isolated from ob/ob mice display type 1 11beta-hydroxysteroid dehydrogenase activity, i.e. in intact cells the reductive reaction prevails, leading from dehydrocorticosterone to corticosterone. Expression of type 1 11beta-HSD mRNA was detected by reverse transcriptase-polymerase chain reaction in islets isolated from ob/ob mice and also from human tissue. Incubation of beta-cells in the presence of 11-dehydrocorticosterone leads to a dose-dependent inhibition of insulin release, indicating cellular activation of 11-dehydrocorticosterone to the receptor ligand, further confirmed by reporter gene assays. Inhibition of 11beta-HSD activity by carbenoxolone reverses inhibition of insulin release. The presence of 11beta-HSD in islets supports the concept that reactivation of inert circulating hormone precursors in a cell-specific manner plays a major role in glucocorticoid physiology in rodents and man. |
| first_indexed | 2024-03-07T00:52:55Z |
| format | Journal article |
| id | oxford-uuid:87013ca0-c80a-4315-945b-ce33dc06531f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:52:55Z |
| publishDate | 2000 |
| record_format | dspace |
| spelling | oxford-uuid:87013ca0-c80a-4315-945b-ce33dc06531f2022-03-26T22:07:54ZType 1 11beta -hydroxysteroid dehydrogenase mediates glucocorticoid activation and insulin release in pancreatic islets.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:87013ca0-c80a-4315-945b-ce33dc06531fEnglishSymplectic Elements at Oxford2000Davani, BKhan, AHult, MMårtensson, EOkret, SEfendic, SJörnvall, HOppermann, UMetabolic transformation of glucocorticoid hormones constitutes a determinant of their cell-specific effects. The most important reaction for this class of steroids is the reversible C11 keto/beta-hydroxyl conversion between receptor-binding 11beta-OH steroids and the nonbinding 11-oxo compounds, carried out by 11beta-hydroxysteroid dehydrogenases (11beta-HSDs). In this study, we determined the role of glucocorticoid conversion by 11beta-HSD in pancreatic islets and its function in the regulation of insulin release. Pancreatic islets isolated from ob/ob mice display type 1 11beta-hydroxysteroid dehydrogenase activity, i.e. in intact cells the reductive reaction prevails, leading from dehydrocorticosterone to corticosterone. Expression of type 1 11beta-HSD mRNA was detected by reverse transcriptase-polymerase chain reaction in islets isolated from ob/ob mice and also from human tissue. Incubation of beta-cells in the presence of 11-dehydrocorticosterone leads to a dose-dependent inhibition of insulin release, indicating cellular activation of 11-dehydrocorticosterone to the receptor ligand, further confirmed by reporter gene assays. Inhibition of 11beta-HSD activity by carbenoxolone reverses inhibition of insulin release. The presence of 11beta-HSD in islets supports the concept that reactivation of inert circulating hormone precursors in a cell-specific manner plays a major role in glucocorticoid physiology in rodents and man. |
| spellingShingle | Davani, B Khan, A Hult, M Mårtensson, E Okret, S Efendic, S Jörnvall, H Oppermann, U Type 1 11beta -hydroxysteroid dehydrogenase mediates glucocorticoid activation and insulin release in pancreatic islets. |
| title | Type 1 11beta -hydroxysteroid dehydrogenase mediates glucocorticoid activation and insulin release in pancreatic islets. |
| title_full | Type 1 11beta -hydroxysteroid dehydrogenase mediates glucocorticoid activation and insulin release in pancreatic islets. |
| title_fullStr | Type 1 11beta -hydroxysteroid dehydrogenase mediates glucocorticoid activation and insulin release in pancreatic islets. |
| title_full_unstemmed | Type 1 11beta -hydroxysteroid dehydrogenase mediates glucocorticoid activation and insulin release in pancreatic islets. |
| title_short | Type 1 11beta -hydroxysteroid dehydrogenase mediates glucocorticoid activation and insulin release in pancreatic islets. |
| title_sort | type 1 11beta hydroxysteroid dehydrogenase mediates glucocorticoid activation and insulin release in pancreatic islets |
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