SMALL AMOUNTS OF FRUCTOSE MARKEDLY AUGMENT NET HEPATIC GLUCOSE-UPTAKEIN THE CONSCIOUS DOG

Fructose activates glucokinase by releasing the enzyme from its inhibi tory protein in Liver. To examine the importance of acute activation o f glucokinase in regulating hepatic glucose uptake, the effect of intr aportal infusion of a small amount of fructose on net hepatic glucose uptake (NHGU) was examined in 42 h-fasted conscious dogs. Isotopic ([3 -H-3] and [U-C-14]glucose) and arteriovenous difference methods were u sed. Each study consisted of an equilibration period (-90 to -30 min), a control period (-30 to 0 min), and a hyperglycemic/hyperinsulinemic period (0-390 min). During the latter period, somatostatin (489 pmol . kg(-1) . min(-1)) was given, along with intraportal insulin (7.2 pmo l . kg(-1) . min(-1)) and glucagon (0.5 ng . kg(-1) . min(-1)). In thi s way, the liver sinusoidal insulin level was fixed at four times basa l (456 +/- 60 pmol/l), and liver sinusoidal glucagon level was kept ba sal (46 +/- 6 ng/l). Glucose was infused through a peripheral vein to create hyperglycemia (12.5 mmol/l plasma). Hyperglycemic hyperinsuline mia (no fructose) sw-itched net hepatic glucose balance (micromoles pe r kilogram per minute) from output (11.3 +/- 1.4) to uptake (14.7 +/- 1.7) and net lactate balance (micromoles per kilogram per minute) from uptake (6.5 +/- 2.1) to output (4.4 +/- 1.5). Fructose was infused in traportally at a rate of 1.7, 3.3, or 6.7 mu mol . kg(-1) . min(-1), s tarting at 120, 210, or 300 min, respectively. In the three periods, p ortal blood fructose increased from <6 to 113 +/- 14, 209 +/- 29, and 426 +/- 62 mu mol/l, and net hepatic fructose uptake increased from 0. 03 +/- 0.01 to 1.3 +/- 0.4, 2.3 +/- 0.7, and 5.1 +/- 0.6 mu mol . kg(- 1) . min(-1), respectively. NHGU increased to 41 +/- 3, 54 +/- 5, and 69 +/- 8 mu mol kg(-1) . min(-1), respectively, and net hepatic lactat e output increased to 11.0 +/- 3.2, 15.3 +/- 2.7, and 22.4 +/- 2.8 mu mol . kg(-1) . min(-1) in the three fructose periods, respectively. Th e amount of [3H]glucose incorporated into glycogen was equivalent to 6 9 +/- 3% of [H-3]glucose taken up by the Liver. These data suggest tha t glucokinase translocation within the hepatocyte is a major determina nt of hepatic glucose uptake by the dog in vivo.