To determine the role of the glucose gradient between the hepatoportal system (HPS) and the central nervous system (CNS) in regulating hepatic glucose uptake, experiments were conducted with seven conscious dogs using a hepatic venous catheterization technique. With the infusion of somatostatin (0.8 µg · 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 infusion (Ginf) according to the following three periods: 1) peripheral glucose infusion period (PE), Ginf alone; 2) portal glucose infusion period (PO), Ginf plus constant glucose infusion into the portal vein (GIRPV, 55.6 μmol · kg−1 · min−1); 3) portal and brain glucose infusion period (PO+CNS), Ginf and GIRPV plus additional glucose infusion into the unilateral carotid and vertebral arteries to abolish the positive glucose gradient between HPS and CNS. Arterial plasma glucose levels were clamped during the three periods (8.1 ± 0.1, PE; 8.2 ± 0.1, PO; 8.2 ± 0.1 mmol/l, PO+CNS). During PO, when a positive glucose gradient was promoted between HPS and CNS, the net hepatic 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 µmol · kg−1 · min−1, PE; P < 0.01). However, this decrease in the NHGB significantly increased during PO+CNS, when the glucose gradient between HPS and CNS was minimized, compared with PO (−21.7 ± 3.2 µmol · kg−1 · min−1 , P < 0.05). We conclude that a positive glucose gradient between HPS and CNS is an important regulatory factor of hepatic glucose uptake, but other factors also play important roles because minimizing the glucose gradient between HPS and CNS diminished the net hepatic glucose uptake by 50%.
Augmentation of Hepatic Glucose Uptake by a Positive Glucose Gradient Between Hepatoportal and Central Nervous Systems
CNS, central nervous system; GIRCA, glucose infusion into the carotid artery; Ginf, glucose infusion; HERG, hepatic extraction rate of glucose; HPS, the hepatoportal system; LH, lateral hypothalamus; NHGB, net hepatic glucose balance; NHGU, net hepatic glucose uptake; PE, peripheral glucose infusion period; PGU, peripheral glucose uptake; PO, portal glucose infusion period; PO+CNS, carotid and vertebral artery glucose infusion period; TGI, total glucose infusion rate; VMH, ventromedial hypothalamus.
Munehide Matsuhisa, Toyohiko Morishima, Itsuro Nakahara, Tadahiro Tomita, Yuichi Shiba, Minoru Kubota, Masahiki Wada, Tsutomu Kanda, Masashi Kubota, Ryuzo Kawamori, Yoshimitsu Yamasaki; Augmentation of Hepatic Glucose Uptake by a Positive Glucose Gradient Between Hepatoportal and Central Nervous Systems. Diabetes 1 July 1997; 46 (7): 1101–1105. https://doi.org/10.2337/diab.46.7.1101
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