The Determinants of Insulin Extraction in the Isolated Perfused Rat Liver

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Abstract
The effect of hepatic blood flow and portal insulin concentration on insulin extraction during one passage through the isolated perfused rat liver was studied. The percentage of insulin extracted was constant over the physiological range of blood flows (4 to 28 ml/min). The total amount of insulin extracted increased as the input concentration was raised from 48 to 4860 µU/ml with the highest level of extraction being approximately 700 µU of insulin per gram of liver per minute. When square wave input pulses of 243 to 4860 µU/ml were presented, about 5% of this insulin was retained and then released by the liver for periods up to 15 minutes after the cessation of the input. The possible roles of glucose and glucagon as regulators of insulin extraction were studied. Glucose (300 mg/dl), as compared with no glucose, led to a significant reduction of insulin extraction (22% vs. 38%, p < 0.001). Glucagon had no effect on insulin extraction in the presence of constant levels of glucose. It is concluded, therefore, that glucose may increase circulating insulin levels not only by its well known stimulation of insulin secretion by the pancreas, but also by inhibiting insulin extraction by the liver. 1 Supported by Grant BMS 75-04049 from the National Science Foundation. Portions of this paper have been published in abstract form (Honey and Price, 1977).