The IgG from a patient (Italy 2 [I2]) with hypoglycemia, due to autoantibodies to the insulin receptor, was purified on protein A Sepharose into two fractions that were tested in various human tissues and cells. The IgG fraction that bound protein A (absorbed IgG [IgGa]) nearly completely inhibited the binding of 125I-labeled insulin to various cells or tissues (placenta, IM-9, adipocytes, HEp-2-larynx cells, Epstein-Barr virus lymphocytes) but not greater than 50% of 125I-labeled insulin binding to human liver membranes. Conversely, both the IgG fraction from this patient, which did not bind protein A (flow-through IgG [IgGb]), and the IgGa fraction from a second similar patient (Italy 1 [I-1]) almost completely inhibited the binding of 125I-labeled insulin to liver membranes. The IgGa fraction from patient I-2 did not change receptor affinity because 50% inhibition of 125I-labeled insulin binding was not affected by either the presence or absence of these IgG fractions. Furthermore, liver binding data were not due to cross-reaction of 125I-labeled insulin to the insulinlike growth factor I receptor, and treatment of liver membranes with neuraminidase did not alter the inhibitory effect of the IgGa fraction from patient I-2 on 125I-labeled insulin binding to liver. Binding inhibition experiments performed with cells transfected with and overexpressing the -12 (human insulin receptor [HIR]-A) or the +12 (HIR-B) variant of HIR revealed that the IgGa fraction from patient I-2 inhibited 125I-labeled insulin binding to the HIR-A receptor but not to the HIR-B receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Sesti, G., Marini, M.A., Montemurro, A., Condorelli, L., Borboni, P., Haring, H.U., et al. (1992). Evidence that two naturally occurring human insulin receptor alpha-subunit variants are immunologically distinct. DIABETES, 41(1), 6-11.

Evidence that two naturally occurring human insulin receptor alpha-subunit variants are immunologically distinct

MARINI, MARIA ADELAIDE;MONTEMURRO, ANTONIO;BORBONI, PATRIZIA;LAURO, RENATO
1992-01

Abstract

The IgG from a patient (Italy 2 [I2]) with hypoglycemia, due to autoantibodies to the insulin receptor, was purified on protein A Sepharose into two fractions that were tested in various human tissues and cells. The IgG fraction that bound protein A (absorbed IgG [IgGa]) nearly completely inhibited the binding of 125I-labeled insulin to various cells or tissues (placenta, IM-9, adipocytes, HEp-2-larynx cells, Epstein-Barr virus lymphocytes) but not greater than 50% of 125I-labeled insulin binding to human liver membranes. Conversely, both the IgG fraction from this patient, which did not bind protein A (flow-through IgG [IgGb]), and the IgGa fraction from a second similar patient (Italy 1 [I-1]) almost completely inhibited the binding of 125I-labeled insulin to liver membranes. The IgGa fraction from patient I-2 did not change receptor affinity because 50% inhibition of 125I-labeled insulin binding was not affected by either the presence or absence of these IgG fractions. Furthermore, liver binding data were not due to cross-reaction of 125I-labeled insulin to the insulinlike growth factor I receptor, and treatment of liver membranes with neuraminidase did not alter the inhibitory effect of the IgGa fraction from patient I-2 on 125I-labeled insulin binding to liver. Binding inhibition experiments performed with cells transfected with and overexpressing the -12 (human insulin receptor [HIR]-A) or the +12 (HIR-B) variant of HIR revealed that the IgGa fraction from patient I-2 inhibited 125I-labeled insulin binding to the HIR-A receptor but not to the HIR-B receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/09 - Medicina Interna
eng
Con Impact Factor ISI
Placenta; Cell Line; Hypoglycemia; Female; Genetic Variation; Lupus Erythematosus, Systemic; Humans; Insulin-Like Growth Factor I; Kinetics; Insulin; Immunoglobulin G; Macromolecular Substances; Liver; Receptor, Insulin; Pregnancy; Adipose Tissue; Antibodies, Monoclonal; Cell Membrane
Sesti, G., Marini, M.A., Montemurro, A., Condorelli, L., Borboni, P., Haring, H.U., et al. (1992). Evidence that two naturally occurring human insulin receptor alpha-subunit variants are immunologically distinct. DIABETES, 41(1), 6-11.
Sesti, G; Marini, Ma; Montemurro, A; Condorelli, L; Borboni, P; Haring, H; Ullrich, A; Goldfine, I; De Pirro, R; Lauro, R
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/53385
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