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dc.contributor.authorParikh, Hemang
dc.contributor.authorCarlsson, Emma
dc.contributor.authorJohansson, Lovisa E
dc.contributor.authorStorgaard, Heidi
dc.contributor.authorPoulsen, Pernille
dc.contributor.authorLadd, Christine
dc.contributor.authorSchulze, P. Christian
dc.contributor.authorMazzini, Michael J
dc.contributor.authorJensen, Christine Bjørn
dc.contributor.authorKrook, Anna
dc.contributor.authorBjörnholm, Marie
dc.contributor.authorTornqvist, Hans
dc.contributor.authorZierath, Juleen R
dc.contributor.authorRidderstråle, Martin
dc.contributor.authorVaag, Allan
dc.contributor.authorGroop, Leif C
dc.contributor.authorChutkow, William Alexander
dc.contributor.authorSaxena, Richa
dc.contributor.authorAltshuler, David Matthew
dc.contributor.authorLee, Richard Theodore
dc.contributor.authorMootha, Vamsi Krishna
dc.date.accessioned2011-04-28T04:19:44Z
dc.date.issued2007
dc.identifier.citationParikh, Hemang, Emma Carlsson, William A. Chutkow, Lovisa E. Johansson, Heidi Storgaard, Pernille Poulsen, Richa Saxena, et al. 2007. TXNIP Regulates Peripheral Glucose Metabolism in Humans. PLoS Medicine 4(5): e158.en_US
dc.identifier.issn1549-1277en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4878922
dc.description.abstractBackground: Type 2 diabetes mellitus (T2DM) is characterized by defects in insulin secretion and action. Impaired glucose uptake in skeletal muscle is believed to be one of the earliest features in the natural history of T2DM, although underlying mechanisms remain obscure. Methods and Findings: We combined human insulin/glucose clamp physiological studies with genome-wide expression profiling to identify thioredoxin interacting protein (TXNIP) as a gene whose expression is powerfully suppressed by insulin yet stimulated by glucose. In healthy individuals, its expression was inversely correlated to total body measures of glucose uptake. Forced expression of TXNIP in cultured adipocytes significantly reduced glucose uptake, while silencing with RNA interference in adipocytes and in skeletal muscle enhanced glucose uptake, confirming that the gene product is also a regulator of glucose uptake. TXNIP expression is consistently elevated in the muscle of prediabetics and diabetics, although in a panel of 4,450 Scandinavian individuals, we found no evidence for association between common genetic variation in the TXNIP gene and T2DM. Conclusions: TXNIP regulates both insulin-dependent and insulin-independent pathways of glucose uptake in human skeletal muscle. Combined with recent studies that have implicated TXNIP in pancreatic β-cell glucose toxicity, our data suggest that TXNIP might play a key role in defective glucose homeostasis preceding overt T2DM.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pmed.0040158en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1858708/pdf/en_US
dash.licenseLAA
dc.subjectdiabetes and endocrinologyen_US
dc.subjectgenetics and genomicsen_US
dc.subjectphysiologyen_US
dc.subjectendocrinologyen_US
dc.subjectdiabetesen_US
dc.subjectgeneticsen_US
dc.subjectnutrition and metabolismen_US
dc.titleTXNIP Regulates Peripheral Glucose Metabolism in Humansen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS Medicineen_US
dash.depositing.authorSaxena, Richa
dc.date.available2011-04-28T04:19:44Z
dash.affiliation.otherHMS^Anaesthesia-Massachusetts General Hospitalen_US
dash.affiliation.otherHMS^Medicine-Massachusetts General Hospitalen_US
dash.affiliation.otherHMS^Geneticsen_US
dash.affiliation.otherHMS^Medicine-Massachusetts General Hospitalen_US
dash.affiliation.otherHMS^Systems Biologyen_US
dc.identifier.doi10.1371/journal.pmed.0040158*
dash.authorsorderedfalse
dash.contributor.affiliatedAltshuler, David
dash.contributor.affiliatedChutkow, William
dash.contributor.affiliatedSaxena, Richa
dash.contributor.affiliatedMootha, Vamsi
dash.contributor.affiliatedLee, Richard


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