Parallel decreases in the expression of receptors for insulin and insulin-like growth factor I in a mutant human fibroblast line.
The receptors for insulin and the insulin-like growth factor (IGF) I are two structurally homologous disulfide-linked multisubunit complexes of apparent Mr = 350,000. The similar subunit structures of these two types of receptors suggested that their genetic expression might be affected by common genetic defects. We have examined this possibility in an insulin-resistant, diabetic patient who exhibits decreased insulin binding activity. The receptors for IGF-I and insulin in skin fibroblasts from this patient were affinity labeled with 125I-IGF-I and 125I-insulin, respectively, and visualized by electrophoresis and autoradiography in polyacrylamide gels. Control fibroblasts exhibited the usual affinity labeling of the disulfide-linked Mr = 350,000 insulin and IGF-I receptor structures. The intensity of labeling of both receptor types in the patient's fibroblasts was less than in control fibroblasts. Binding data indicated that this decrease is due to a decreased receptor number with little or no decrease in affinity for the respective ligands. The high-affinity IGF-II receptor in fibroblasts affinity labeled with 125I-IGF-II or 125I-IGF-I consists of a single polypeptide not disulfide linked to any other membrane component. The molecular size and intensity of labeling of the IGF-II receptor in the patient's fibroblasts were unaltered when compared with those of controls. These observations suggest that a common genetic defect alters the expression of the homologous receptor structures for insulin and IGF-I.
D002460:Cell Line; D003920:Diabetes Mellitus / Q000235:genetics*; D004351:Drug Resistance; D005347:Fibroblasts; D005796:Genes; D006801:Humans; D007328:Insulin / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*; D017451:Receptors, Somatomedin
D007328:Insulin; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D011972:Receptor, Insulin