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Title: Reduction of glucose uptake through inhibition of hexose transporters and enhancement of their endocytosis by methylglyoxal in Saccharomyces cerevisiae.
Authors: Yoshida, Aya
Wei, Dandan
Nomura, Wataru
Izawa, Shingo
Inoue, Yoshiharu  kyouindb  KAKEN_id
Author's alias: 井上, 善晴
Keywords: hexose transporter
Saccharomyces cerevisiae
methylglyoxal
endocytosis
Rsp5
phospholipase C
Issue Date: 2-Jan-2012
Publisher: American Society for Biochemistry and Molecular Biology
Journal title: The Journal of biological chemistry
Volume: 287
Issue: 1
Start page: 701
End page: 711
Abstract: Diabetes 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.
Rights: © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
This 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。
URI: http://hdl.handle.net/2433/169680
DOI(Published Version): 10.1074/jbc.M111.322222
PubMed ID: 22094464
Appears in Collections:Journal Articles

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