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 alpha1 domain of the major histocompatibility comple x class I antigen (MHC class I), e.g. D(k)-(61-85) and D(k)-(62-85), h ave been shown previously to augment glucose uptake in insulin-stimula ted cells and to inhibit insulin receptor internalization (Stagsted, J ., Reaven, G. M., Hansen, T., Goldstein, A., and Olsson, L. (1990) Cel l 62, 297-307). We now report that these peptides inhibit by 80-100% t he internalization of glucose transporters (GLUT4) and insulin-like gr owth factor II (IGF-II) receptors in insulin-stimulated cells and corr espondingly double insulin-stimulated glucose transport activity and t he number of GLUT4 and IGF-II receptors on the cell surface. In additi on, the peptides enhance the apparent affinity about 3-fold of IGF-II binding to its receptor. It is concluded that the effects of the pepti des on glucose transport and IGF-II binding are a consequence of the p eptide-mediated inhibition of internalization of GLUT4 and IGF-II rece ptor. The active peptides are derived from the alpha1 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.