Linked Life Data

16324917

Source:http://linkedlifedata.com/resource/pubmed/id/16324917

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-12-5
pubmed:abstractText
Dexamethasone inhibits insulin secretion from isolated islets. In the present experiments, possible underlying biochemical mechanisms responsible for defective secretion were explored. Dexamethasone (1 micromol/L) had no immediate deleterious effect on 15 mmol/L glucose-induced insulin release from perifused rat islets. However, a 3-hour preincubation period with 1 micromol/L dexamethasone resulted in parallel reductions in both the first (64%) and second phases (74%) of 15 mmol/L glucose-induced insulin secretion monitored during a dynamic perifusion. When measured after the perifusion, there were no differences in insulin content or in the capacity of control or dexamethasone-treated islets to use glucose. Dexamethasone (1 micromol/L) preexposure also reduced phorbol ester- and potassium-induced secretion. In additional experiments, islets were labeled for 3 hours with 3H-inositol in the presence or absence of 1 micromol/L dexamethasone. The steroid did not affect total 3H-inositol incorporation during the labeling period. However, the capacity of 15 mmol/L glucose, 30 mmol/L KCl, and 100 micromol/L carbachol to activate phospholipase C (PLC), monitored by the accumulation of labeled inositol phosphates, was significantly reduced in dexamethasone-pretreated islets. Inclusion of the nuclear glucocorticoid receptor antagonist RU486 (mifepristone, 10 micromol/L) abolished the adverse effects of dexamethasone on both glucose-induced inositol phosphate accumulation and insulin secretion. Quantitative Western blot analyses revealed that the islet contents of PLCdelta1, PLCbeta1, beta2, beta3, and protein kinase C alpha were unaffected by dexamethasone pretreatment. These findings demonstrate that dexamethasone pretreatment impairs insulin secretion via a genomic action and that impaired activation of the PLC/protein kinase C signaling system is involved in the evolution of its inhibitory effect on secretion.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0026-0495
pubmed:author
pubmed:issnType
Print
pubmed:volume
55
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
35-42
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:16324917-Animals, pubmed-meshheading:16324917-Blotting, Western, pubmed-meshheading:16324917-Depression, Chemical, pubmed-meshheading:16324917-Dexamethasone, pubmed-meshheading:16324917-Enzyme Activation, pubmed-meshheading:16324917-Glucose, pubmed-meshheading:16324917-Hormone Antagonists, pubmed-meshheading:16324917-Inositol Phosphates, pubmed-meshheading:16324917-Insulin, pubmed-meshheading:16324917-Islets of Langerhans, pubmed-meshheading:16324917-Isoenzymes, pubmed-meshheading:16324917-Kinetics, pubmed-meshheading:16324917-Male, pubmed-meshheading:16324917-Mifepristone, pubmed-meshheading:16324917-Potassium, pubmed-meshheading:16324917-Protein Kinase C, pubmed-meshheading:16324917-Rats, pubmed-meshheading:16324917-Rats, Sprague-Dawley, pubmed-meshheading:16324917-Tetradecanoylphorbol Acetate, pubmed-meshheading:16324917-Type C Phospholipases
pubmed:year
2006
pubmed:articleTitle
Dexamethasone suppresses phospholipase C activation and insulin secretion from isolated rat islets.
pubmed:affiliation
Yale University School of Nursing, New Haven, CT 06536-0740, USA. walter.zawalich@yale.edu
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural