Linked Life Data

15047606

Source:http://linkedlifedata.com/resource/pubmed/id/15047606

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-3-29
pubmed:abstractText
Increased flux through the hexosamine biosynthetic pathway and increased O-linked glycosylation (N-acetylglucosamine [O-GlcNAc]) of proteins have been implicated in insulin resistance. Previous research in 3T3-L1 adipocytes indicated that insulin-stimulated glucose uptake and phosphorylation of Akt were reduced after incubation with O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc; 100 micromol/l), an inhibitor of the O-GlcNAcase that catalyzes removal of O-GlcNAc from proteins. Therefore, in this study, we tested the effects of PUGNAc on skeletal muscle. Incubation of rat epitrochlearis muscles for 19 h with 100 micromol/l PUGNAc resulted in a marked increase in O-GlcNAcylation of multiple proteins. Incubation with PUGNAc reduced glucose transport with a physiologic insulin concentration without affecting glucose transport without insulin or with supraphysiologic insulin. PUGNAc did not significantly alter insulin-stimulated phosphorylation of Akt (serine and threonine) or its substrates glycogen synthase kinase (GSK)3 alpha and GSK3 beta. Insulin stimulated a dose-dependent (12.0 > 0.6 > 0 nmol/l) increase in the phosphorylation of a 160-kDa protein detected using an antibody against an Akt substrate phosphomotif. PUGNAc treatment did not alter phosphorylation of this protein. These results indicate that PUGNAc is an effective inhibitor of O-GlcNAcase in skeletal muscle and suggest that O-GlcNAc modification of proteins can induce insulin resistance in skeletal muscle independent of attenuated phosphorylation of Akt, GSK 3 alpha, GSK3 beta, and a 160-kDa protein with an Akt phosphomotif.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0012-1797
pubmed:author
pubmed:issnType
Print
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
921-30
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:15047606-Acetylglucosamine, pubmed-meshheading:15047606-Animals, pubmed-meshheading:15047606-Biological Transport, pubmed-meshheading:15047606-Glucose, pubmed-meshheading:15047606-Glycosylation, pubmed-meshheading:15047606-Insulin, pubmed-meshheading:15047606-Insulin Resistance, pubmed-meshheading:15047606-Kinetics, pubmed-meshheading:15047606-Male, pubmed-meshheading:15047606-Muscle, Skeletal, pubmed-meshheading:15047606-Muscle Proteins, pubmed-meshheading:15047606-Oximes, pubmed-meshheading:15047606-Phenylcarbamates, pubmed-meshheading:15047606-Phosphorylation, pubmed-meshheading:15047606-Phosphoserine, pubmed-meshheading:15047606-Phosphothreonine, pubmed-meshheading:15047606-Protein Processing, Post-Translational, pubmed-meshheading:15047606-Rats, pubmed-meshheading:15047606-Rats, Wistar
pubmed:year
2004
pubmed:articleTitle
Prolonged incubation in PUGNAc results in increased protein O-Linked glycosylation and insulin resistance in rat skeletal muscle.
pubmed:affiliation
Department of Kinesiology, University of Wisconsin-Madison, Madison, Wisconsin, USA. edarias@umich.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.