AUGMENTATION OF HEPATIC GLUCOSE-UPTAKE BY A POSITIVE GLUCOSE GRADIENTBETWEEN HEPATOPORTAL AND CENTRAL NERVOUS SYSTEMS

To determine the role of the glucose gradient between the hepatoportal system (HPS) and the central nervous system (CNS) in regulating hepat ic glucose uptake, experiments were conducted with seven conscious dog s using a hepatic venous catheterization technique. With the infusion of somatostatin (0.8 pg. kg(-1).min(-1)), glucagon (0.65 ng.kg(-1).min (-1)), and insulin (27 pmol. kg(-1).min(-1)), arterial glucose levels could be maintained at 8 mmol/l by adjusting the intravenous glucose i nfusion (G(inf)) according to the following three periods: 1) peripher al glucose infusion period (PE), G(inf) alone; 2) portal gin cose infu sion period (PO), G(inf) plus constant glucose infusion into the porta l vein (GIR(PV), 55.6 mu mol.kg(-1). min(-1)); 3) portal and brain glu cose infusion period (PO+CNS), G(inf) and GIR(PV) plus additional gluc ose infusion into the unilateral carotid and vertebral arteries to abo lish the positive glucose gradient between HPS and CNS. Arterial plasm a glucose levels were clamped during the three periods (8.1 +/- 0.1, P E; 8.2 +/- 0.1, PO; 8.2 +/- 0.1 mmol/l, PO+CNS). During PO, when a pos itive glucose gradient was promoted between HPS and CNS, the net hepat ic glucose balance (NHGB) determined by the difference between hepatic glucose inflow and outflow was significantly lower than that of PE (- 41.5 +/- 5.3, PO vs. -7.5 +/- 3.4 pmol.kg(-1).min(-1), PE; P < 0.01). However, this decrease in the NHGB significantly increased during PO+C NS, when the glucose gradient between HPS and CNS was minimized, compa red with PO (-21.7 +/- 3.2 mu mol.kg(-1).min(-1), P < 0.05). We conclu de that a positive glucose gradient between HPS and CNS is an importan t regulatory factor of hepatic glucose uptake, but other factors also play important roles because minimizing the glucose gradient between H PS and CNS diminished the net hepatic glucose uptake by 50%.