Differential Modification of Activities of the High-Affinity and Low-Affinity Insulin Receptors of 3T3-L1 Fibroblasts by Phosphonolipidsin Vivo

Abstract

The low-affinity and high-affinity forms of the insulin receptor respond differently to modifications of cellular phospholipid content in mouse 3T3-L1 fibroblastsin vivo.When cells are cultured with 2-aminoethylphosphonate the resulting phosphonolipid, which has previously been demonstrated to prevent the insulin-induced differentiation of the fibroblasts into adipocytes [J. D. Smithet al., Biochem. Arch.8,339–344 (1992)] results in alterations in both the affinity for insulin and receptor number of the low-affinity receptor while leaving the high-affinity receptor unaffected. That this phospholipid modification induces a specific change in the cellular insulin effect is demonstrated by the lack of alteration in the mobilization of GLUT-4 and glucose transport in the lipid modified cells. The results suggest that this specific cellular phospholipid modification will be useful in dissecting the specific functions of the two forms of the mammalian insulin receptor.