Modeling glucose control on endogenous glucose production in nonsteady state: necessity of direct and delayed signalling

So far the modilities of glucose control on endogenous glucose production (EGP) under dynamic conditions have been poorly investigated. In the present study we developed models to describe glucose control on EGP under nonsteady-state conditions. The data base consisted of experiments during which insulin was maintained at the basal level, glucose concentration exhibited a meal-like profile, and a glucose tracer was infused in such a way to clamp tracer glucose specific activity. This optimal protocol allowed us: 1) to rule out the possibly confounding effect of hyperinsulinemia on the assessment of glucose control on EGP, and 2) to ensure an accurate assessment of the time course of EGP during the nonsteady state. Three models of increasing complexity were formulated, employing different combinations of two modalities of glucose control on EGP, one exerted by glucose in plasma and the other one by glucose in a remote glucose compartment. Each model provided indices measuring glucose inhibitory action on EGP (glucose effectiveness) and the delay of glucose action on EGP. The best model is the one which embodies both direct and delayed glucose control on EGP.