Inhibition of internalization of glucose transporters and IGF-II receptors. Mechanism of action of MHC class I-derived peptides which augment the insulin response in rat adipose cells.
Peptides from the alpha 1 domain of the major histocompatibility complex class I antigen (MHC class I), e.g. Dk-(61-85) and Dk-(62-85), have been shown previously to augment glucose uptake in insulin-stimulated cells and to inhibit insulin receptor internalization (Stagsted, J., Reaven, G. M., Hansen, T., Goldstein, A., and Olsson, L. (1990) Cell 62, 297-307). We now report that these peptides inhibit by 80-100% the internalization of glucose transporters (GLUT4) and insulin-like growth factor II (IGF-II) receptors in insulin-stimulated cells and correspondingly double insulin-stimulated glucose transport activity and the number of GLUT4 and IGF-II receptors on the cell surface. In addition, the peptides enhance the apparent affinity about 3-fold of IGF-II binding to its receptor. It is concluded that the effects of the peptides on glucose transport and IGF-II binding are a consequence of the peptide-mediated inhibition of internalization of GLUT4 and IGF-II receptor. The active peptides are derived from the alpha 1 domain of a MHC class I molecule, suggesting that the latter is involved in regulation of internalization of cell surface integral membrane proteins such as the GLUT4 and IGF-II and insulin receptors.
Stagsted
J
J
Receptron, Inc., Concord, California 94520.
Olsson
L
L
Holman
G D
GD
Cushman
S W
SW
Satoh
S
S
D019325:3-O-Methylglucose; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D004822:Epididymis; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D015395:Histocompatibility Antigens Class I / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008757:Methylglucosides / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000302:isolation & purification / Q000378:metabolism*; D009124:Muscle Proteins; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017527:Receptor, IGF Type 2 / Q000302:isolation & purification / Q000378:metabolism*
D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D015395:Histocompatibility Antigens Class I; D007328:Insulin; D008757:Methylglucosides; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D010446:Peptide Fragments; D017527:Receptor, IGF Type 2; C495694:Slc2a4 protein, rat; D019325:3-O-Methylglucose; D007335:Insulin-Like Growth Factor II