Endothelin-1 increases glucose transporter glut1 mRNA accumulation in 3T3-L1 adipocytes by a mitogen-activated protein kinase-dependent pathway.
The mechanism of enhancing glucose transport by prolonged endothelin-1 (ET-1) treatment of 3T3-L1 adipocytes was examined. Western and Northern blot analyses indicated that ET-1 increased the amount of both GLUT1 protein and mRNA. The degradation rate of GLUT1 mRNA as measured in the presence of actinomycin D, nevertheless, was not significantly altered by ET-1. Whereas various inhibitors for distinct signalling pathways were tested, only the mitogen-activated protein kinase (MAPK) kinase inhibitor, PD98059, was found to decrease significantly the enhancing effect of ET-1. Similar extent of inhibition was observed in cells pretreated with pertussis toxin (PT). Immunoblot analysis revealed that ET-1 may stimulate a transient phosphorylation of p42/p44 MAPK and both PT and PD98059 inhibited this stimulation. In addition, the effect of ET-1 on GLUT1 mRNA accumulation was inhibited by PD98059 and cycloheximide, implying that a trans-activation was involved. Taken together, these results suggest that ET-1 may induce GLUT1 gene expression by a MAPK-dependent mechanism.
Fong
J C
JC
Institute of Biochemistry, National Yang-Ming University, Taipei, Taiwan, ROC. ffong@ym.edu.tw
Kao
Y S
YS
Tsai
H
H
Ho
L T
LT
D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D015152:Blotting, Northern; D019332:Endothelin-1 / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D007700:Kinetics; D020935:MAP Kinase Signaling System; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D005419:Flavonoids; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C495678:Slc2a1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D005947:Glucose; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one