The IgG from a patient (Italy 2 [I-2]) 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 >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. The data reported herein demonstrate that the two naturally occurring insulin-receptor variants are immunologically distinct and indicate that the HIR-B variant is predominantly expressed in liver compared with other human tissues.
Evidence That Two Naturally Occurring Human Insulin Receptor α-Subunit Variants Are Immunologically Distinct
Giorgio Sesti, Maria Adelaide Marini, Antonio Montemurro, Luigi Condorelli, Patrizia Borboni, Hans-Ulrich Haring, Axel Ullrich, Ira D Goldfine, Roberto De Pirro, Renato Lauro; Evidence That Two Naturally Occurring Human Insulin Receptor α-Subunit Variants Are Immunologically Distinct. Diabetes 1 January 1992; 41 (1): 6–11. https://doi.org/10.2337/diab.41.1.6
Download citation file: