Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2007) 14 P280

ECE2007 Poster Presentations (1) (659 abstracts)

Non-genomic glucocorticoid effects on insulin secretion

Greisa Vila , Ludwig Wagner , Anastasia Nabokikh & Anton Luger

Department of Medicine III, Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria.

Glucocorticoids act directly on pancreatic islets suppressing insulin secretion from the beta cells through a genomic mechanism of slow onset. We present here data on immediate actions of dexamethasone on two models of insulin secretion: RINm5F and INS-1 beta cell lines. Under normal glucose concentrations, dexamethasone rapidly (within minutes) decreased insulin secretion about 30%. Under hypoglycaemic conditions (glucose reduced to 50% for 1 hour) dexamethasone increased insulin release. Both these effects were present within 10 minutes and not in longer (up to 1 hour) stimulations. They were completely abolished by preincubation with pertussis toxin, slightly inhibited by the intracellular glucocorticoid receptor (iGR) antagonist mifepristone (RU486) and unaltered by the transcription inhibitor cycloheximide.

Western blotting experiments revealed that serum glucocorticoid kinase 1 (SGK1, a known early transcriptional target of glucocorticoids also known to regulate epithelial ion transport) rapidly translocated to the membrane following Dexamethasone treatment. Rapid changes were also seen in the cellular distribution of the calcium-binding protein secretagogin. Incubation with pertussis toxin 30 minutes prior to Dexamethasone stimulation, abolished not only the above effects, but also the translocation of the iGR to the nucleus and the increase in SGK1 mRNA levels (starting 30 minutes after stimulation and measured by quantitative RT-PCR). While further mechanisms are still under investigation, we conclude that glucocorticoids act non-genomically on the beta cells affecting insulin secretion, protein distribution and possibly ion exchange. They have a dual role in homeostatic and stress conditions, similar to that seen in the fast feed-back to the HPA axis.

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