Insulin removal in man: in vivo evidence for a receptor-mediated process.
To evaluate the in vivo participation of insulin receptors in both hepatic and extrahepatic removal of insulin, compartmental kinetic analysis of insulin behavior was performed in a patient with blocked receptors due to endogenous antiinsulin receptor antibodies. Using the standard three-compartment simulation of insulin behavior, the responses to both a 5-U injection of exogenous insulin and a 4.2-U secretion of endogenous insulin subsequent to tolbutamide injection were examined. In response to both exogenous and endogenous insulin, hepatic removal of insulin was reduced to less than 18% of the insulin exposure (normal, 40-60%). The metabolic clearance of insulin was reduced from the normal level of 520 ml/min to less than 120 ml/min, consistent with a reduction in receptor-mediated removal of insulin from the blood. These studies propose quantitative parameters for insulin receptor function in hepatic and extrahepatic removal of insulin in man.
D000328:Adult; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D011972:Receptor, Insulin / Q000502:physiology*; D014044:Tolbutamide / Q000494:pharmacology
D007328:Insulin; D014044:Tolbutamide; D011972:Receptor, Insulin