Distinct biologically active receptors for insulin, insulin-like growth factor I, and insulin-like growth factor II in cultured skeletal muscle cells.

The expression of insulin-like growth factor (IGF) receptors at the cell surface and the changes in IGF responsiveness during differentiation were studied in the L6 skeletal muscle cell line. Throughout the entire developmental sequence, distinct receptors for IGF I and IGF I1 that differed in structure and peptide specificity could be demonstrated. During differentiation, both 12'I-IGF I and 1261-IGF I1 binding to the L6 cells decreased as a result of a 3-4-fold reduction in receptor number, whereas 1251-insulin binding increased. Under nonreducing conditions, disuccinimidyl suberate cross-linked 1251-IGF I and 1251-IGF I1 to two receptor complexes with apparent M, > 300,000 (type I) and 220,000 (type 11). Under reducing conditions, the apparent molecular weight of the type I receptor changed to M, 130,000 (distinct from the 120,000 insulin receptor) and the type I1 receptor changed to 250,000. IGF I and IGF I1 both stimulated 2-deoxy-~-glucose and a-aminoisobutyric acid uptake in the L6 cells with a potency close to that of insulin, apparently through interaction with their own receptors. The stimulatory effects of IGF I1 correlated with its affinity for the type I1 but not the type I IGF receptor, as measured by inhibition of affinity labeling, whereas the effects of IGF I correlated with its ability to inhibit labeling of the type I receptor. In spite of the decrease in type I and type I1 receptor number, stimulation of Z-deoxyglucose and a-aminoisobutyric acid uptake by the two IGFs increased during differentiation. The insulin-like growth factors (IGFsl) are a family of polypeptide hormones that have close structural and functional homologies with insulin. The two IGF types found in human plasma (IGF I and IGF 11) have approximately 70% amino acid sequence identity with each other and almost 50% identity with human insulin (1,2). Insulin and IGFs produce similar biological effects in most cells, including stimulation