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dc.contributor.authorYoshida, Ayaja
dc.contributor.authorWei, Dandanja
dc.contributor.authorNomura, Wataruja
dc.contributor.authorIzawa, Shingoja
dc.contributor.authorInoue, Yoshiharuja
dc.contributor.alternative井上, 善晴ja
dc.description.abstractDiabetes mellitus is characterized by an impairment of glucose uptake even though blood glucose levels are increased. Methylglyoxal is derived from glycolysis and has been implicated in the development of diabetes mellitus, because methylglyoxal levels in blood and tissues are higher in diabetic patients than in healthy individuals. However, it remains to be elucidated whether such factors are a cause, or consequence, of diabetes. Here, we show that methylglyoxal inhibits the activity of mammalian glucose transporters using recombinant Saccharomyces cerevisiae cells genetically lacking all hexose transporters but carrying cDNA for human GLUT1 or rat GLUT4. We found that methylglyoxal inhibits yeast hexose transporters also. Glucose uptake was reduced in a stepwise manner following treatment with methylglyoxal, i.e. a rapid reduction within 5 min, followed by a slow and gradual reduction. The rapid reduction was due to the inhibitory effect of methylglyoxal on hexose transporters, whereas the slow and gradual reduction seemed due to endocytosis, which leads to a decrease in the amount of hexose transporters on the plasma membrane. We found that Rsp5, a HECT-type ubiquitin ligase, is responsible for the ubiquitination of hexose transporters. Intriguingly, Plc1 (phospholipase C) negatively regulated the endocytosis of hexose transporters in an Rsp5-dependent manner, although the methylglyoxal-induced endocytosis of hexose transporters occurred irrespective of Plc1. Meanwhile, the internalization of hexose transporters following treatment with methylglyoxal was delayed in a mutant defective in protein kinase C.ja
dc.publisherAmerican Society for Biochemistry and Molecular Biologyja
dc.rights© 2012 by The American Society for Biochemistry and Molecular Biology, Inc.ja
dc.rightsThis is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。ja
dc.subjecthexose transporterja
dc.subjectSaccharomyces cerevisiaeja
dc.subjectphospholipase Cja
dc.subject.meshBiological Transport/drug effectsja
dc.subject.meshEndocytosis/drug effectsja
dc.subject.meshEndosomal Sorting Complexes Required for Transport/metabolismja
dc.subject.meshGlucose Transporter Type 1/antagonists & inhibitorsja
dc.subject.meshGlucose Transporter Type 4/antagonists & inhibitorsja
dc.subject.meshHypoglycemic Agents/pharmacologyja
dc.subject.meshMonosaccharide Transport Proteins/antagonists & inhibitorsja
dc.subject.meshMonosaccharide Transport Proteins/metabolismja
dc.subject.meshProtein Kinase C/metabolismja
dc.subject.meshProteolysis/drug effectsja
dc.subject.meshSaccharomyces cerevisiae/cytologyja
dc.subject.meshSaccharomyces cerevisiae/drug effectsja
dc.subject.meshSaccharomyces cerevisiae/metabolismja
dc.subject.meshSaccharomyces cerevisiae Proteins/metabolismja
dc.subject.meshTOR Serine-Threonine Kinases/metabolismja
dc.subject.meshType C Phospholipases/metabolismja
dc.subject.meshUbiquitin-Protein Ligase Complexes/metabolismja
dc.titleReduction of glucose uptake through inhibition of hexose transporters and enhancement of their endocytosis by methylglyoxal in Saccharomyces cerevisiae.ja
dc.type.niitypeJournal Articleja
dc.identifier.jtitleThe Journal of biological chemistryja
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