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 a ) was estimated in a non-steady state caused by the infusion of glucose (exogenous increase of R a ) or glucagon (increase of hepatic glucose output) in unanesthetized dogs with indwelling arterial and venous catheters. First, R a was measured with 2- 3 H-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) 14 C-glucose, was started. Exponential functions were fitted to the two specific activity curves. The second tracer made it possible to calculate R a 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) 14 C-glucose as a tracer gave about 10% lower values for R a than tritiated glucose.