Insulin kinetics after portal and peripheral injection of [125I] insulin: II. Experiments in the intact dog.

Insulin metabolism in man is usually investigated by peripheral injection of the hormone, whereas native insulin undergoes hepatic extraction prior to mixing in the general circulation. To quantify this difference, in 10 dogs [125I] insulin was injected into a peripheral vein, and the initial distribution volume (IDV), the metabolic clearance rate (MCR), and the mean transit time (t) were computed from the plasma disappearance curve of the immunoprecipitable activity. The splenic vein was then cannulated under pentobarbital anesthesia, and the parameters were again computed from the peripheral activity after portal introduction of the tracer. The MCR after portal injection [15.1 +/- (SE) 1.1 ml/min per kg] was greater (P is less than 0.001) than the MCR after peripheral administration (13.4 +/- 0.9 ml/min per kg). Also, IDV was larger (P is less than 0.01) after portal injection (167 +/- 12 vs. 138 +/- 10 ml/kg). Mean transit times did not change significantly. Insulin secretion rate (0.29 +/-0.04 mU/min per kg) and body insulin mass (7.03 +/- 1.5 mU/kg) were also measured. An estimate of hepatic extraction was obtained from the difference between the clearance rate values calculated following portal and peripheral injection. Under our experimental conditions, hepatic retention of insulin was found to be 19.6% (range 9.6-36.2%). The method is recommended for investigations in man.