Linked Life Data

1352288

Source:http://linkedlifedata.com/resource/pubmed/id/1352288

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
1992-8-6
pubmed:abstractText
To investigate whether GTP concentrations can be a regulatory step in exocytotic hormone secretion, we treated isolated rat islets with mycophenolic acid (MPA) or mizoribine, two selective inhibitors of de novo GTP synthesis. When islets were cultured overnight in purine-free medium containing the drug, MPA reduced GTP levels by up to 81 +/- 1%; guanine circumvented this block via the nucleotide "salvage" pathway. MPA concomitantly inhibited glucose (16.7 mM)-induced insulin secretion in batch-type incubations (or perifusions), by up to 68% at 50 micrograms/ml. Although the inhibition of secretion occurred over a similar concentration range as the reduction in total GTP content, the two variables were not directly correlated. However, the secretory effects also were prevented by adding guanine, but not hypoxanthine or xanthine, to the culture medium. Similar results for GTP content and insulin release were seen using mizoribine. Insulin content was modestly (-18%) reduced by MPA but indices of fractional release (release/insulin content) were also markedly impaired. Although MPA also reduced ATP levels more modestly (-39%) and increased UTP (+87%), these were not the cause of the secretory defect since adenine restored ATP and UTP nearly to normal, but did not alter the reduction in GTP content or insulin secretion. MPA also inhibited secretion induced by amino acid or by a phorbol ester but had virtually no effect on release induced by a depolarizing concentration of K+, suggesting that GTP depletion does not merely impede Ca+ influx or directly block Ca(2+)-activated exocytosis. However, a severe reduction of GTP content did not prevent the pertussis toxin-sensitive inhibition of insulin release induced by epinephrine, suggesting that the function of heterotrimeric GTP-binding proteins is not limited by ambient GTP concentrations. Although these studies do not elucidate the exact site(s) in the exocytotic cascade which depend on intact GTP stores, they do provide the first direct evidence that GTP is required (and can be rate limiting) for insulin release.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
267
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
12517-27
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:1352288-Adenosine Triphosphate, pubmed-meshheading:1352288-Animals, pubmed-meshheading:1352288-Chromatography, High Pressure Liquid, pubmed-meshheading:1352288-Epinephrine, pubmed-meshheading:1352288-Exocytosis, pubmed-meshheading:1352288-Guanosine Triphosphate, pubmed-meshheading:1352288-IMP Dehydrogenase, pubmed-meshheading:1352288-Insulin, pubmed-meshheading:1352288-Islets of Langerhans, pubmed-meshheading:1352288-Kinetics, pubmed-meshheading:1352288-Male, pubmed-meshheading:1352288-Mycophenolic Acid, pubmed-meshheading:1352288-Pertussis Toxin, pubmed-meshheading:1352288-Rats, pubmed-meshheading:1352288-Rats, Inbred Strains, pubmed-meshheading:1352288-Ribonucleosides, pubmed-meshheading:1352288-Uridine Triphosphate, pubmed-meshheading:1352288-Virulence Factors, Bordetella
pubmed:year
1992
pubmed:articleTitle
Selective inhibitors of GTP synthesis impede exocytotic insulin release from intact rat islets.
pubmed:affiliation
Section of Endocrinology, University of Wisconsin, Madison.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.