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- Title
Evidence that two naturally occurring human insulin receptor alpha-subunit variants are immunologically distinct.
- Authors
Sesti, Giorgio; Marini, Maria Adelaide; Montemurro, Antonio; Condorelli, Luigi; Borboni, Patrizia; Haring, Hans-Ulrich; Ullrich, Axel; Goldfine, Ira D.; De Pirro, Roberto; Lauro, Renato; Sesti, G; Marini, M A; Montemurro, A; Condorelli, L; Borboni, P; Haring, H U; Ullrich, A; Goldfine, I D; De Pirro, R; Lauro, R
- 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)
- Publication
Diabetes, 1992, Vol 41, Issue 1, p6
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.41.1.6