Linked Life Data

10342815

Source:http://linkedlifedata.com/resource/pubmed/id/10342815

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1999-6-8
pubmed:abstractText
To examine the mechanism by which free fatty acids (FFAs) induce insulin resistance in vivo, awake chronically catheterized rats underwent a hyperinsulinemic-euglycemic clamp with or without a 5-h preinfusion of lipid/heparin to raise plasma FFA concentrations. Increased plasma FFAs resulted in insulin resistance as reflected by a approximately 35% reduction in the glucose infusion rate (P < 0.05 vs. control). The insulin resistance was associated with a 40-50% reduction in 13C nuclear magnetic resonance (NMR)-determined rates of muscle glycogen synthesis (P < 0.01 vs. control) and muscle glucose oxidation (P < 0.01 vs. control), which in turn could be attributed to a approximately 25% reduction in glucose transport activity as assessed by 2-[1,2-3H]deoxyglucose uptake in vivo (P < 0.05 vs. control). This lipid-induced decrease in insulin-stimulated muscle glucose metabolism was associated with 1) a approximately 50% reduction in insulin-stimulated insulin receptor substrate (IRS)-1-associated phosphatidylinositol (PI) 3-kinase activity (P < 0.05 vs. control), 2) a blunting in insulin-stimulated IRS-1 tyrosine phosphorylation (P < 0.05, lipid-infused versus glycerol-infused), and 3) a four-fold increase in membrane-bound, or active, protein kinase C (PKC) theta (P < 0.05 vs. control). We conclude that acute elevations of plasma FFA levels for 5 h induce skeletal muscle insulin resistance in vivo via a reduction in insulin-stimulated muscle glycogen synthesis and glucose oxidation that can be attributed to reduced glucose transport activity. These changes are associated with abnormalities in the insulin signaling cascade and may be mediated by FFA activation of PKC theta.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0012-1797
pubmed:author
pubmed:issnType
Print
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1270-4
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:10342815-Animals, pubmed-meshheading:10342815-Deoxyglucose, pubmed-meshheading:10342815-Enzyme Activation, pubmed-meshheading:10342815-Fatty Acids, Nonesterified, pubmed-meshheading:10342815-Insulin, pubmed-meshheading:10342815-Insulin Receptor Substrate Proteins, pubmed-meshheading:10342815-Insulin Resistance, pubmed-meshheading:10342815-Isoenzymes, pubmed-meshheading:10342815-Magnetic Resonance Spectroscopy, pubmed-meshheading:10342815-Male, pubmed-meshheading:10342815-Muscle, Skeletal, pubmed-meshheading:10342815-Phosphatidylinositol 3-Kinases, pubmed-meshheading:10342815-Phosphoproteins, pubmed-meshheading:10342815-Phosphorylation, pubmed-meshheading:10342815-Protein Kinase C, pubmed-meshheading:10342815-Rats, pubmed-meshheading:10342815-Rats, Sprague-Dawley, pubmed-meshheading:10342815-Signal Transduction, pubmed-meshheading:10342815-Tyrosine, pubmed-meshheading:10342815-Zinc Fingers
pubmed:year
1999
pubmed:articleTitle
Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signaling cascade.
pubmed:affiliation
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8020, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't