Heterogeneity of human liver, muscle, and adipose tissue insulin receptor.
We have studied the structure and function of the human insulin receptor in liver, skeletal muscle and adipose tissue. The alpha-subunit of the insulin receptor for liver, muscle and adipose tissue migrated on SDS-PAGE with Mrs 137632 +/- 216, 134034 +/- 1080, and 133575 +/- 165, respectively (p less than 0.05). Treatment of these receptors with neuraminidase decreased their molecule sizes and eliminated the relative size differences between the receptors. Three monoclonal antibodies (5A1, 10D9, and 20H3), directed towards different epitopes of the human insulin receptor alpha-subunit were used to probe immunological differences among the receptors. Antibodies 5A1 and 20H3 recognized all the receptors, whereas 10D9 recognized muscle and adipose tissue receptors but not liver receptors. The mobility of insulin receptor beta-subunit in the absence of insulin was the same in all tissues with a similar phosphorylation-induced decrease in mobility in SDS-PAGE in the presence of insulin. However, insulin stimulated autophosphorylation per receptor was different being greatest (p less than 0.05) in muscle (334 +/- 104 32P cpm) and similar in adipose tissue (114 +/- 10) and liver (183 +/- 68). These studies indicate, therefore, that the human insulin receptor is heterogeneous among the major target tissues for insulin, and raise the possibility that this heterogeneity may account for tissues' specific differences in insulin's biological messages.
Caro
J F
JF
Department of Medicine, School of Medicine, East Carolina University, Greenville, North Carolina 27858-4354.
Raju
S M
SM
Sinha
M K
MK
Goldfine
I D
ID
Dohm
G L
GL
D000273:Adipose Tissue / Q000032:analysis* / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000276:immunology; D001345:Autoradiography; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007118:Immunoassay; D007328:Insulin / Q000378:metabolism; D008099:Liver / Q000032:analysis* / Q000378:metabolism; D008970:Molecular Weight; D009132:Muscles / Q000032:analysis* / Q000378:metabolism; D011972:Receptor, Insulin / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D012044:Regression Analysis
D000911:Antibodies, Monoclonal; D007328:Insulin; D011972:Receptor, Insulin