DIFFERENTIAL MODIFICATION OF ACTIVITIES OF THE HIGH-AFFINITY AND LOW-AFFINITY INSULIN-RECEPTORS OF 3T3-L1 FIBROBLASTS BY PHOSPHONOLIPIDS IN-VIVO

The low-affinity and high-affinity forms of the insulin receptor respo nd differently to modifications of cellular phospholipid content in mo use 3T3-L1 fibroblasts in vivo. When cells are cultured with 2-aminoet hylphosphonate the resulting phosphonolipid, which has previously been demonstrated to prevent the insulin-induced differentiation of the fi broblasts into adipocytes [J. D. Smith et al., Biochem. Arch. 8, 339-3 44 (1992)] results in alterations in both the affinity for insulin and receptor number of the low-affinity receptor while leaving the high-a ffinity receptor unaffected. That this phospholipid modification induc es a specific change in the cellular insulin effect is demonstrated by the lack of alteration in the mobilization of GLUT-4 and glucose tran sport in the lipid modified cells. The results suggest that this speci fic cellular phospholipid modification will be useful in dissecting th e specific functions of the two forms of the mammalian insulin recepto r. (C) 1996 Academic Press, Inc.