Linked Life Data

10973946

Source:http://linkedlifedata.com/resource/pubmed/id/10973946

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
45
pubmed:dateCreated
2000-11-27
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
275
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
34841-4
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:10973946-11-beta-Hydroxysteroid Dehydrogenases, pubmed-meshheading:10973946-Animals, pubmed-meshheading:10973946-Anti-Ulcer Agents, pubmed-meshheading:10973946-Carbenoxolone, pubmed-meshheading:10973946-Corticosterone, pubmed-meshheading:10973946-Diabetes Mellitus, Type 2, pubmed-meshheading:10973946-Dose-Response Relationship, Drug, pubmed-meshheading:10973946-Genes, Reporter, pubmed-meshheading:10973946-Glucocorticoids, pubmed-meshheading:10973946-Glucose, pubmed-meshheading:10973946-Humans, pubmed-meshheading:10973946-Hydroxysteroid Dehydrogenases, pubmed-meshheading:10973946-Insulin, pubmed-meshheading:10973946-Islets of Langerhans, pubmed-meshheading:10973946-Isoenzymes, pubmed-meshheading:10973946-Kinetics, pubmed-meshheading:10973946-Ligands, pubmed-meshheading:10973946-Mice, pubmed-meshheading:10973946-Mice, Knockout, pubmed-meshheading:10973946-Mice, Mutant Strains, pubmed-meshheading:10973946-Pancreas, pubmed-meshheading:10973946-RNA, Messenger, pubmed-meshheading:10973946-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:10973946-Tissue Distribution, pubmed-meshheading:10973946-Transcription, Genetic
pubmed:year
2000
pubmed:articleTitle
Type 1 11beta -hydroxysteroid dehydrogenase mediates glucocorticoid activation and insulin release in pancreatic islets.
pubmed:affiliation
Department of Molecular Medicine, Karolinska Hospital, S 171 76 Stockholm, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't