Fibroblasts from a leprechaun patient have defects in insulin binding and insulin receptor autophosphorylation. 1988

J A Maassen, and M P Klinkhamer, and G C van der Zon, and H Sips, and W Möller, and H M Krans, and D Lindhout, and F A Beemer
Department of Medical Biochemistry, Sylvius Laboratories, University Hospital, Leiden, The Netherlands.

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.

UI MeSH Term Description Entries
D007231 Infant, Newborn An infant during the first 28 days after birth. Neonate,Newborns,Infants, Newborn,Neonates,Newborn,Newborn Infant,Newborn Infants
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D007333 Insulin Resistance Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS. Insulin Sensitivity,Resistance, Insulin,Sensitivity, Insulin
D007334 Insulin-Like Growth Factor I A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor. IGF-I,Somatomedin C,IGF-1,IGF-I-SmC,Insulin Like Growth Factor I,Insulin-Like Somatomedin Peptide I,Insulin Like Somatomedin Peptide I
D008297 Male Males
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D011956 Receptors, Cell Surface Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands. Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D011972 Receptor, Insulin A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE. Insulin Receptor,Insulin Receptor Protein-Tyrosine Kinase,Insulin Receptor alpha Subunit,Insulin Receptor beta Subunit,Insulin Receptor alpha Chain,Insulin Receptor beta Chain,Insulin-Dependent Tyrosine Protein Kinase,Receptors, Insulin,Insulin Receptor Protein Tyrosine Kinase,Insulin Receptors
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D003847 Deoxyglucose 2-Deoxy-D-arabino-hexose. An antimetabolite of glucose with antiviral activity. 2-Deoxy-D-glucose,2-Deoxyglucose,2-Desoxy-D-glucose,2 Deoxy D glucose,2 Deoxyglucose,2 Desoxy D glucose

Related Publications

J A Maassen, and M P Klinkhamer, and G C van der Zon, and H Sips, and W Möller, and H M Krans, and D Lindhout, and F A Beemer
March 1990, Biochemical and biophysical research communications,
J A Maassen, and M P Klinkhamer, and G C van der Zon, and H Sips, and W Möller, and H M Krans, and D Lindhout, and F A Beemer
May 1986, Molecular and cellular endocrinology,
J A Maassen, and M P Klinkhamer, and G C van der Zon, and H Sips, and W Möller, and H M Krans, and D Lindhout, and F A Beemer
October 1988, The Journal of clinical investigation,
J A Maassen, and M P Klinkhamer, and G C van der Zon, and H Sips, and W Möller, and H M Krans, and D Lindhout, and F A Beemer
May 1988, The Journal of clinical endocrinology and metabolism,
J A Maassen, and M P Klinkhamer, and G C van der Zon, and H Sips, and W Möller, and H M Krans, and D Lindhout, and F A Beemer
May 1992, Metabolism: clinical and experimental,
J A Maassen, and M P Klinkhamer, and G C van der Zon, and H Sips, and W Möller, and H M Krans, and D Lindhout, and F A Beemer
June 1986, The Biochemical journal,
J A Maassen, and M P Klinkhamer, and G C van der Zon, and H Sips, and W Möller, and H M Krans, and D Lindhout, and F A Beemer
June 1990, The Journal of laboratory and clinical medicine,
J A Maassen, and M P Klinkhamer, and G C van der Zon, and H Sips, and W Möller, and H M Krans, and D Lindhout, and F A Beemer
February 1989, Biochemistry,
J A Maassen, and M P Klinkhamer, and G C van der Zon, and H Sips, and W Möller, and H M Krans, and D Lindhout, and F A Beemer
February 1993, The Journal of biological chemistry,
J A Maassen, and M P Klinkhamer, and G C van der Zon, and H Sips, and W Möller, and H M Krans, and D Lindhout, and F A Beemer
June 1988, The Journal of biological chemistry,
Copied contents to your clipboard!