Insulin down-regulates expression of the insulin-responsive glucose transporter (GLUT4) gene: effects on transcription and mRNA turnover.
Insulin rapidly represses expression of the gene encoding the insulin-responsive glucose transporter (GLUT4) in 3T3-L1 mouse adipocytes. Upon exposure to the hormone the cellular level of GLUT4 mRNA falls (t1/2 approximately 2.5 hr) to 20-30% of its initial level within 10 hr. This is followed by a similar decrease in the level of GLUT4 protein. Down-regulation of GLUT4 mRNA is a result of both rapid repression of transcription of the GLUT4 gene and an increased rate of turnover of the GLUT4 message. As a consequence of prolonged exposure to insulin, 3T3-L1 adipocytes lose their capacity for acute stimulation of hexose uptake by insulin. These findings provide an explanation for the resistance of glucose uptake to insulin in adipose tissue observed in non-insulin-dependent (type 2) diabetes mellitus, particularly that associated with hyperinsulinemia and obesity.
Flores-Riveros
J R
JR
Department of Biological Chemistry, Johns Hopkins University, School of Medicine, Baltimore, MD 21205.
McLenithan
J C
JC
Ezaki
O
O
Lane
M D
MD
D016475:3T3 Cells; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D015536:Down-Regulation; D051275:Glucose Transporter Type 4; D006601:Hexoses / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D009124:Muscle Proteins; D012333:RNA, Messenger / Q000302:isolation & purification / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic
D051275:Glucose Transporter Type 4; D006601:Hexoses; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; C495693:Slc2a4 protein, mouse; D007334:Insulin-Like Growth Factor I