RODENT INSULIN-RECEPTORS ARE IMMUNOLOGICALLY DIFFERENT FROM OTHER MAMMALIAN INSULIN-RECEPTORS

Four monoclonal antibodies (MA-5, MA-10, MA-20, and MA-51) and one pol yclonal antibody (ARS-2) against human insulin receptor were used to i mmunoprecipitate the insulin receptor from several species which had b een photolabeled with N (is an element of B29)-monoazidobenzoyl-[I-125 ]iodoinsulin. All four monoclonal antibodies immunoprecipitated human insulin receptor from human placental membranes. MA-10 and MA-51, but not MA-5 or MA-20, immunoprecipitated insulin receptors from liver pla sma membranes of rabbit, guinea pig, dog, cattle, pig, and chicken. No ne of the monoclonal antibodies immunoprecipitated insulin receptors o f rat, mouse, hamster, or chinchilla. In contrast, all of the insulin receptors were immunoprecipitated by the polyclonal anti-insulin recep tor antibody, ARS-2. MA-10 and MA-51 compared with [I-125]iodoinsulin for binding to guinea pig and rabbit liver plasma membranes in a fashi on similar to insulin, although less effectively. MA-51 also mimicked the action of insulin by stimulating lipogenesis and autophosphorylati on of the insulin receptor beta subunit in isolated rabbit adipocytes. The results suggest that insulin receptors of mammals, other than rod ent, share with human insulin receptor the same epitope(s) recognized by MA-10 and MA-51. Rodent insulin receptors, with the exception of gu inea pig, are different. We speculate that the difference lies in the amino acid sequence 485-599 of the alpha subunit of the insulin recept or. (C) 1994 Academic Press, Inc.