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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
36
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pubmed:dateCreated |
2002-9-2
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pubmed:abstractText |
To determine the mechanism(s) for insulin resistance induced by fatty acids, we measured the ability of insulin to activate phosphoinositide 3-kinase (PI3K) and multiple distal pathways in rats. Following a 5-h infusion of lipid or glycerol (control), rats underwent a euglycemic hyperinsulinemic clamp. Insulin stimulated IRS-1-associated PI3K activity in muscle of glycerol-infused rats 2.4-fold but had no effect in lipid-infused rats. IRS-2- and phosphotyrosine-associated PI3K activity were increased 3.5- and 4.8-fold, respectively, by insulin in glycerol-infused rats but only 1.6- and 2.3-fold in lipid-infused rats. Insulin increased Akt1 activity 3.9-fold in glycerol-infused rats, and this was impaired 41% in lipid-infused rats. Insulin action on Akt2 and p70S6K were not impaired, whereas activation of protein kinase C lambda/zeta activity was reduced 47%. Insulin inhibited glycogen synthase kinase 3alpha (GSK-3alpha) activity by 30% and GSK-3beta activity by approximately 65% and increased protein phosphatase-1 activity by 40-47% in both glycerol- and lipid-infused rats. Insulin stimulated glycogen synthase activity 2.0-fold in glycerol-infused rats but only 1.4-fold in lipid-infused rats. Thus, 1) elevation of fatty acids differentially affects insulin action on pathways distal to PI3K, impairing activation of Akt1 and protein kinase C lambda/zeta and 2) insulin action on glycogen synthase can be regulated independent of effects on GSK-3 and protein phosphatase-1 activity in vivo.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/AKT1 protein, Arabidopsis,
http://linkedlifedata.com/resource/pubmed/chemical/Arabidopsis Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Glycerol,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoprotein Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Plant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Phosphatase 1,
http://linkedlifedata.com/resource/pubmed/chemical/protein kinase C lambda,
http://linkedlifedata.com/resource/pubmed/chemical/protein kinase C zeta
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
6
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pubmed:volume |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
32915-22
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:12095990-Animals,
pubmed-meshheading:12095990-Arabidopsis Proteins,
pubmed-meshheading:12095990-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:12095990-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:12095990-Enzyme Activation,
pubmed-meshheading:12095990-Fatty Acids,
pubmed-meshheading:12095990-Glycerol,
pubmed-meshheading:12095990-Glycogen Synthase,
pubmed-meshheading:12095990-Glycogen Synthase Kinase 3,
pubmed-meshheading:12095990-Glycogen Synthase Kinases,
pubmed-meshheading:12095990-Insulin,
pubmed-meshheading:12095990-Insulin Antagonists,
pubmed-meshheading:12095990-Isoenzymes,
pubmed-meshheading:12095990-MAP Kinase Signaling System,
pubmed-meshheading:12095990-Male,
pubmed-meshheading:12095990-Muscles,
pubmed-meshheading:12095990-Phosphoprotein Phosphatases,
pubmed-meshheading:12095990-Plant Proteins,
pubmed-meshheading:12095990-Potassium Channels,
pubmed-meshheading:12095990-Protein Isoforms,
pubmed-meshheading:12095990-Protein Kinase C,
pubmed-meshheading:12095990-Protein Phosphatase 1,
pubmed-meshheading:12095990-Rats,
pubmed-meshheading:12095990-Rats, Sprague-Dawley,
pubmed-meshheading:12095990-Signal Transduction,
pubmed-meshheading:12095990-Time Factors
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pubmed:year |
2002
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pubmed:articleTitle |
Fatty acid infusion selectively impairs insulin action on Akt1 and protein kinase C lambda /zeta but not on glycogen synthase kinase-3.
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pubmed:affiliation |
Diabetes Unit, Division of Endocrinology and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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