Estimation of hepatic glucose output in non steady state. The simultaneous use of 2 ³H glucose and ¹⁴C glucose in the dog

The rate of appearance of glucose (R) was estimated in a non steady state caused by the infusion of glucose (exogenous increase of R) or glucagon (increase of hepatic glucose output) in unanesthetized dogs with indwelling arterial and venous catheters. First, R was measured with 2-³H glucose according to the primed constant rate infusion technique in steady state, then with the onset of the perturbation the infusion of a second tracer, (U) ¹⁴C glucose, was started. Exponential functions were fitted to the two specific activity curves. The second tracer made it possible to calculate R during the non steady state without the need to assume a definite value for the 'miscible' glucose space (V). The latter could also be calculated and it proved to be a single exponential function of time elapsed from the start of the perturbation. In the first few minutes the glucose load (10 or 15 mg/kg min for 120 min) caused a sharp fall of hepatic glucose output. This was followed by a rise of various degrees before the endogenous glucose output reached the steady state at about 50 or 70% below the base line values. During the glucose load, in steady state (U) ¹⁴C glucose as a tracer gave about 10% lower values for R than tritiated glucose.