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 polyclonal antibody (ARS-2) against human insulin receptor were used to immunoprecipitate the insulin receptor from several species which had been photolabeled with N epsilon B29-monoazido-benzoyl-[125I]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 plasma membranes of rabbit, guinea pig, dog, cattle, pig, and chicken. None of the monoclonal antibodies immunoprecipitated insulin receptors of rat, mouse, hamster, or chinchilla. In contrast, all of the insulin receptors were immunoprecipitated by the polyclonal anti-insulin receptor antibody, ARS-2. MA-10 and MA-51 compared with [125I]iodoinsulin for binding to guinea pig and rabbit liver plasma membranes in a fashion similar to insulin, although less effectively. MA-51 also mimicked the action of insulin by stimulating lipogenesis and autophosphorylation of the insulin receptor beta subunit in isolated rabbit adipocytes. The results suggest that insulin receptors of mammals, other than rodent, share with human insulin receptor the same epitope(s) recognized by MA-10 and MA-51. Rodent insulin receptors, with the exception of guinea pig, are different. We speculate that the difference lies in the amino acid sequence 485-599 of the alpha subunit of the insulin receptor.
Tong
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Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada.
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Moule
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Goldfine
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Yip
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D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000345:Affinity Labels; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000911:Antibodies, Monoclonal; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D002645:Chickens; D002682:Chinchilla; D006224:Cricetinae; D004285:Dogs; D000939:Epitopes / Q000276:immunology; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007328:Insulin / Q000493:pharmacokinetics; D008055:Lipids / Q000096:biosynthesis; D051379:Mice; D010766:Phosphorylation; D011233:Precipitin Tests; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D011972:Receptor, Insulin / Q000737:chemistry / Q000276:immunology*; D013045:Species Specificity; D013552:Swine
D000345:Affinity Labels; D000906:Antibodies; D000911:Antibodies, Monoclonal; D000939:Epitopes; D007328:Insulin; D008055:Lipids; D011972:Receptor, Insulin