Linked Life Data

9882452

Source:http://linkedlifedata.com/resource/pubmed/id/9882452

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1999-2-11
pubmed:abstractText
The cytokine tumor necrosis factor-alpha (TNFalpha) contributes to metabolic changes in disease states such as insulin resistance. However, the mechanism by which TNFalpha alters cellular function in these conditions is poorly understood. Because changes in intracellular calcium concentration plays a critical role in hormone action we investigated the effect of TNFalpha on calcium homeostasis in 3T3-L1 adipocytes. In these studies we show that TNFalpha causes a concentration- and time-dependent decrease in Na+/myo-inositol cotransporter (SMIT) mRNA levels and myo-inositol accumulation as well as a decrease in myo-inositol incorporation into phosphoinositides. These changes coincided with a decrease in endothelin-1-induced phosphatidylinositol (PI) cycle activity in 3T3-L1 adipocytes chronically exposed to TNFalpha. Endothelin-1-induced mobilization of calcium from intracellular stores was also diminished by TNFalpha. The effect of TNFalpha on endothelin-1-induced PI cycle activity and calcium mobilization was not due to a decrease in endothelin receptors. However, TNFalpha did cause a moderate decrease in phosphatidylinositol 4,5-bisphosphate (PIP2)-specific phospholipase C (PLC) activity in 3T3-L1 adipocytes. Combined, a decrease in phosphoinositide production and PIP2-specific PLC activity could be responsible for altering PI cycle activity and the generation of the second messenger myo-inositol 1,4,5-trisphosphate, thereby reducing calcium mobilization. Such changes in intracellular signaling may contribute to the pathophysiology of insulin resistance associated with TNFalpha.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Calcium, http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Endothelin-1, http://linkedlifedata.com/resource/pubmed/chemical/Heat-Shock Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositols, http://linkedlifedata.com/resource/pubmed/chemical/Phosphoinositide Phospholipase C, http://linkedlifedata.com/resource/pubmed/chemical/Phosphoric Diester Hydrolases, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/SLC5A3 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Symporters, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0003-9861
pubmed:author
pubmed:copyrightInfo
Copyright 1999 Academic Press.
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
361
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
241-51
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Endothelin-stimulated Ca2+ mobilization by 3T3-L1 adipocytes is suppressed by tumor necrosis factor-alpha.
pubmed:affiliation
Diabetes-Endocrinology Research Center and Veterans Affairs Medical Center, University of Iowa, Iowa City, Iowa, 52245, USA. myorek@icva.gov
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't