Insulin and glucocorticoids regulate IGFBP-1 expression via a common promoter region.
Hepatic expression of insulin-like growth factor binding protein-1 is regulated by insulin and glucocorticoids. To study underlying mechanisms, rat hepatocytes in primary culture were transfected with deletion mutants and heterologous promoter constructs, identifying a 41 bp region of the rat insulin-like growth factor binding protein-1 promoter which is sufficient to mediate regulation by both insulin and glucocorticoids. Half maximal suppression of promoter activity by insulin occurred at a physiologic concentration, 5 x 10(-10) M, and regulation by insulin was dominant in that insulin suppressed promoter activity at all dexamethasone concentrations. Transfection of rat hepatocytes in primary culture should be a useful approach for exploring the regulation of gene expression by insulin.
Robertson
D G
DG
Department of Medicine, Emory University School of Medicine, Atlanta, GA 30303.
Marino
E M
EM
Thulé
P M
PM
Seneviratne
C K
CK
Murphy
L J
LJ
D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics*; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D016384:Consensus Sequence; D003907:Dexamethasone / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D018970:Insulin-Like Growth Factor Binding Protein 1; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015183:Restriction Mapping; D017384:Sequence Deletion; D012689:Sequence Homology, Nucleic Acid; D013002:Somatomedins / Q000378:metabolism; D014162:Transfection
D002352:Carrier Proteins; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D013002:Somatomedins; D003907:Dexamethasone; D015500:Chloramphenicol O-Acetyltransferase