A negative arterial-portal venous glucose gradient increases net hepatic glucose uptake in euglycemic dogs

We investigated whether a negative arterial-portal venous (a-pv) glucose gr adient, or "portal signal," can increase net hepatic glucose uptake (NHGU) and decrease muscle glucose uptake at euglycemia as it does at hyperglycemi a. Twenty 42-h fasted dogs were studied during a basal and two 120-min eugl ycemic periods (period I and period II). Glucagon was maintained at basal l evels, and insulin was raised 3-fold (3xIns, n = 10) or 15-fold (15xIns, n. = 10). During period I, dogs received glucose only peripherally. During pe riod II, one-half of the dogs continued the peripheral infusion; the other one-half received glucose intraportally (4 mg . kg(-1) . min(-1) and reduce d peripheral glucose infusion). A negative a-pv glucose gradient was presen t during intraportal glucose infusion. All 3xIns and 15xIns dogs had simila r NHGU in period I. In period II, it was 2.1 +/- 0.3 (3xIns) and 2.5 (15xIn s) mg . kg(-1) . min(-1) greater in the presence than in the absence of the portal signal (P < 0.001). The net glucose fractional extraction data para lleled NHGU. In 3xIns, but not in 15xIns, whole body nonhepatic glucose upt ake was lower in the presence of the portal signal than in its absence. In conclusion, in hyperinsulinemic, but not hyperglycemic conditions, the port al signal is effective in activating NHGU. The inhibition of nonhepatic glu cose uptake, on the other hand, is minimal under euglycemic as opposed to h yperglycemic conditions.