Insulin receptors of skeletal muscle: specific insulin binding sites and demonstration of decreased numbers of sites in obese rats.
A membrane preparation was obtained from rat striated muscle. The preparation used has been shown to contain plasma membranes by electron microscopy as well as by enrichment in specific activity of both a plasma membrane enzyme "marker" (5'-nucleotidase) and cell surface 125I-incorporated radioactivity. The characteristics of 125I-insulin binding to this striated muscle preparation were studied, and it was found that 125I-insulin readily and specifically binds to this membrane preparation. The binding reaction was time, pH, and temperature dependent with optimal steady-state binding conditions occurring at 20 degrees C and at pH 7.6. Under these conditions (20 degrees C, pH 7.6) skeletal muscle plasma membranes displayed little ability to degrade insulin. Binding of 125I-insulin was readily inhibited at physiologic concentrations of unlabeled insulin and the specificity of this receptor for insulin was demonstrated by finding that high concentrations of glucagon, b-LH, b-FSH, p-PRL, hCG, TSH, and HGH were without effect on 125I-insulin binding and that insulin analogues inhibited binding in proportion to their biologic activity. When membranes from older, fatter rats were compared to membranes from younger, lean animals, 5'-nucleotidase specific activity and insulin degrading activity were found to be comparable. On the other hand, insulin binding to membrane receptors was decreased 30%-40% in the older, fatter animals. Thus, these studies indicate that (1) specific insulin receptors exist in skeletal muscle plasma membranes, and (2) membranes from older, fatter rats have fewer receptors than those from younger, lean animals.
D000367:Age Factors; D000818:Animals; D001665:Binding Sites; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000378:metabolism*; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D009708:Nucleotidases / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface
D007328:Insulin; D011956:Receptors, Cell Surface; D009708:Nucleotidases