Fibroblasts from a leprechaun patient have defects in insulin binding and insulin receptor autophosphorvlation
Open Access
- 1 August 1988
- journal article
- research article
- Published by Springer Nature in Diabetologia
- Vol. 31 (8) , 612-617
- https://doi.org/10.1007/bf00264769
Abstract
Leprechaunism is an inherited human disorder associated with an extreme resistance of the target cells towards the action of insulin. We have examined the properties of the insulin receptor in fibroblasts from a leprechaun patient (Geldermalsen, the Netherlands). In vitro, severe insulin resistance is reflected by a low level of insulin stimulated uptake of 2-deoxyglucose by these fibroblasts. This defect seems to be caused by a combination of two factors: a low level of insulin binding to intact cells and a strong decrease of insulin stimulated autophosphorylation of the receptor. The stimulation of autophosphorylation by insulin was approximately six-fold in control subjects and less than two-fold in the patient. No abnormalities were observed in the total number of insulin receptors in these cells and the molecular weights of the receptor subunits. In addition, the insulin concentration required for half maximal autophosphorylation is similar for the solubilised receptor from control and patient fibroblasts.Keywords
This publication has 20 references indexed in Scilit:
- Improper expression of insulin receptors on fibroblasts from a leprechaun patientEuropean Journal of Biochemistry, 1988
- The effect of insulin, serum and dexamethasone on mRNA levels for the insulin receptor in the human lymphoblastoic cell line IM-9Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1987
- Decreased kinase activity of insulin receptors from adipocytes of non-insulin-dependent diabetic subjects.Journal of Clinical Investigation, 1987
- Acute insulin action requires insulin receptor kinase activity: introduction of an inhibitory monoclonal antibody into mammalian cells blocks the rapid effects of insulin.Proceedings of the National Academy of Sciences, 1987
- Mapping surface structures of the human insulin receptor with monoclonal antibodies: localization of main immunogenic regions to the receptor kinase domainBiochemistry, 1986
- Human insulin receptor and its relationship to the tyrosine kinase family of oncogenesNature, 1985
- Visualization of the Insulin Receptor by ImmunoblottingDiabetes, 1984
- Extreme Insulin Resistance in Association with Abnormally High Binding Affinity of Insulin Receptors from a Patient with Leprechaunism: Evidence for a Defect Intrinsic to the ReceptorJournal of Clinical Endocrinology & Metabolism, 1982
- Stimulation of glucose incorporation and amino acid transport by insulin and an insulin-like growth factor in fibroblasts with defective insulin receptors cultured from a patient with leprechaunism.Proceedings of the National Academy of Sciences, 1981
- LeprechaunismThe Journal of Pediatrics, 1954