title: Fibroblasts from a patient with leprechaunism are resistant to insulin, epidermal growth factor, and somatomedin C.
abstract: Leprechaunism is a rare inherited disorder characterized by severe intrauterine growth retardation and insulin resistance. Cultured skin fibroblasts from an infant with Leprechaunism were previously reported to show decreased stimulation of DNA synthesis by insulin despite apparently normal binding of [125I]insulin and [125I]somatomedin C. We have now further investigated the growth of this patient's fibroblasts and compared their metabolic responses to insulin and various peptide growth factors with responses in normal foreskin-derived fibroblasts. The doubling time of Leprechaun fibroblasts was prolonged (90 vs. 29 h), and their morphology was abnormal. Stimulation of [3H]glucose uptake was minimal with low insulin levels (1--10 ng/ml) relative to controls, but was comparable at higher insulin concentrations (1--10 micrograms/ml). Stimulation of [3H] aminoisobutyric acid uptake by insulin, epidermal growth factor (EGF), multiplication-stimulating activity, and somatomedin C (Sm-C) in Leprechaun cells was diminished relative to control cells at all concentrations tested. Furthermore, stimulation of [3H]thymidine incorporation in Leprechaum cells by EGF, Sm-C, and fibroblast growth factor was also subnormal. Binding of [125I]EGF to Leprechaun fibroblasts was not decreased. It is concluded that fibroblasts from this patient are resistant to the metabolic effects of insulin, EGF, Sm-C, and fibroblast growth factor. Since receptors for three of these peptides are apparently normal, it is likely that the defect in these cells is at the postreceptor level, perhaps involving a metabolic pathway common to the action of multiple growth factors.
mesh_terms: D000621:Aminoisobutyric Acids / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured; D004351:Drug Resistance; D004392:Dwarfism / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors; D005346:Fibroblast Growth Factors; D005347:Fibroblasts / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007223:Infant; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I; D010455:Peptides / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism; D013002:Somatomedins / Q000494:pharmacology*; D013577:Syndrome; D013936:Thymidine / Q000378:metabolism
chemical_list: D000621:Aminoisobutyric Acids; D010455:Peptides; D011956:Receptors, Cell Surface; D013002:Somatomedins; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D066246:ErbB Receptors; D005947:Glucose; D013936:Thymidine