Abstract
Leprechaunism is characterized by severe intrauterine growth retardation and insulin resistance. We have reported (JCEM 48:495, 1979) that Leprechaun fibroblasts have diminished DNA synthesis in response to insulin or serum, despite apparently normal binding of 125I-insulin and 125I-somatomedin-C. The doubling time of Leprechaun fibroblasts is prolonged (96 vs 48 hrs.), suggesting an aberrant growth mechanism(s). To further characterize the defect in this syndrome, we compared the metabolic responses of Leprechaun and normal skin fibroblasts in culture. Stimulation of 3H-glucose uptake was minimal with low insulin (1-10 ng/ml) relative to control cells, but was comparable at higher insulin concentrations (1-10 μg/ml). Insulin-stimulated 3H-aminoisobutyric acid (3H-AIB) uptake by Leprechaun cells was less than normal at all concentrations tested. Defective responses of Leprechaun cells were not limited to insulin, since EGF also had diminished effects on 3H-AIB uptake and DNA synthesis. 125I-EGF binding, however, was normal. Conclusions: 1) In addition to defective responses to insulin, fibroblasts from our patient are resistant to the effects of EGF. 2) Since receptors for these peptides are apparently normal, it is likely that these cells have a post-receptor defect. 3) We speculate that Leprechaun cells have an alteration in a metabolic pathway which is involved in the action of multiple growth factors.
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Kaplowitz, P., D'Ercole, A. Fibroblasts from a patient with Leprechaunism are resistant to Epidermal Growth Factor (EGF) as well as Insulin. Pediatr Res 15, 1545 (1981). https://doi.org/10.1203/00006450-198112000-00061
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DOI: https://doi.org/10.1203/00006450-198112000-00061