The serum from a patient with lupus nephritis, insulin resistance, and hypoglycemia was studied. This serum both inhibits the binding of 125I-insulin to its receptor and has insulin-like activity on fat cells (see refs. 1 and 2). The IgG fraction from this patient's serum one-half maximally inhibited 125I-insulin binding to IM-9 cells at 1 μM, but did not markedly inhibit 125I-monoclonal antibody binding even at concentrations as high as 4 μM. The IgG was then subjected to affinity chromatography on a protein A-Sepharose column. Four protein peaks were eluted from this column by a step pH gradient from 5.5 to 2.3. Three of the four peaks inhibited 125I-insulin binding to its receptors, but none was more potent than the unfractionated IgG itself. One IgG peak, however, was able to inhibit 125I-monoclonal antibody binding at tenfold lower concentrations than the unfractionated IgG. When the ability of the four IgG fractions to stimulate 2-deoxy[3H]-D-glucose transport in rat adipocytes was studied, two fractions showed stimulatory activity. Compared with unfractionated IgG, one had a weak ability to inhibit 125I-insulin binding, but tenfold more potency to mimic insulin action. The other had a strong ability to inhibit 125I-insulin binding but less potency to mimic insulin action. These studies indicate, therefore, that the serum contains multiple populations of antibodies to the insulin receptor, or portions of the plasma membrane adjacent to the receptor, which have different biologic effects.
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March 01 1984
Characterization of the Serum from a Patient with Insulin Resistance and Hypoglycemia: Evidence for Multiple Populations of Insulin Receptor Antibodies with Different Receptor Binding and Insulin-mimicking Activities
Roberto De Pirro;
Roberto De Pirro
Clinica Medica, Policlinico Umberto I, Università di Rome
Rome, Italy
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Richard A Roth;
Richard A Roth
Cell Biology Laboratory, Harold Brunn Institute, Mount Zion Hospital and Medical Center
San Francisco, California
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Luciano Rossetti;
Luciano Rossetti
Clinica Medica, Policlinico Umberto I, Università di Rome
Rome, Italy
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Ira D Goldfine
Ira D Goldfine
Cell Biology Laboratory, Harold Brunn Institute, Mount Zion Hospital and Medical Center
San Francisco, California
Department of Physiology and Medicine, University of California
San Francisco, California
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Address reprint requests to Roberto De Pirro, M.D., 2ˆ Clinica Medica, Policlinico Umberto I, Viale del Policlinico, 00161 Rome, Italy.
Citation
Roberto De Pirro, Richard A Roth, Luciano Rossetti, Ira D Goldfine; Characterization of the Serum from a Patient with Insulin Resistance and Hypoglycemia: Evidence for Multiple Populations of Insulin Receptor Antibodies with Different Receptor Binding and Insulin-mimicking Activities. Diabetes 1 March 1984; 33 (3): 301–304. https://doi.org/10.2337/diab.33.3.301
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