Measurement and modeling of the transient difference between blood and subcutaneous glucose concentrations in the rat after injection of insulin

The kinetics of the fall in subcutaneous fluid glucose concentration in anesthetized rats (n = 7) after intravenous injection of insulin (0.5 units/kg) was studied by using 5 x 10(-4) cm2 active area, <150-sec 10-90% response time, amperometric glucose sensors. The onset of the decline in the subcutaneous glucose concentration was delayed and statistically different (P < 0.001) from that in blood (8.9 +/- 2.1 min vs. 3.3 +/- 0.5 min). Similarly, the rate of drop in glucose concentration between 6 and 20 min after the insulin injection was different for subcutaneous tissue (3.9 +/- 1.3 mg.dl-1. min-1) and blood (6.8 +/- 2.0 mg.dl-1.min-1) (P = 0.003). The hypoglycemic nadir in subcutaneous fluid occurred 24.5 +/- 6.8 min after that in the blood (P < 0.001). A "forward" mass-transfer model, predicting the subcutaneous glucose concentration from the blood glucose concentrations and an "inverse" model, predicting the blood glucose concentration from the subcutaneous glucose concentration were derived. By using an algorithm based on the latter, the average discrepancy between the measured blood glucose concentration and that estimated from the subcutaneous measurement through the entire 4-hr experiment was reduced from 22.9% to 11.1% (P = 0.025). The maximum discrepancy during the 40-min period after the injection of insulin was reduced from 84.1% to 29.3% (P = 0.006).