The insulin-like growth factor-I (IGF-I) receptor of Chinese hamster ovary (CHO) cells has been characterized in wild type and two mutant CHO lines. The oligosaccharide portion of the IGF-I receptor and/or other non-receptor glycoproteins does not appear to affect IGF-I receptor affinity. This is in sharp contrast to the situation with insulin receptors which appear to be significantly affected by glycosylation changes. Glucose starvation, which forces the wild type cells to become phenotypically identical to one of the mutant cell lines, has no effect on IGF-I binding while it significantly increased insulin binding due to an increase in affinity. A monoclonal antibody to the human IGF-I receptor, alpha-IR3, reacts with the hamster IGF-I receptor equally well in all CHO lines. By using CHO cells, both wild type and mutants, and various lectins, we have determined indirectly that the carbohydrate units of the insulin receptor are heterogenous. Some insulin receptor carbohydrates may play a role at cell surface while others may express more intrinsic properties. In studies with fibroblasts cultured from patients with severe insulin resistance, significantly elevated levels of IGF-I binding was found in 3 of 8 patients with lipoatrophic diabetes. Fibroblasts from an infant with leprechaunism and her phenotypically normal mother both had normal levels of IGF-I binding despite their abnormal insulin binding. Monoclonal antibody alpha-IR3 was able to partially inhibit 125I-insulin binding to both cell lines and the presence of alpha-IR3 in insulin competition curves shifted the dose response curve to the right.
