In vivo portal-hepatic venous gradients of glycogenic precursors and incorporation of D-[3-3H]glucose into liver glycogen in the awake rat.
Male Wistar fed rats were chronically cannulated and fed ground chow for 2 h for 6 days. On the 7th post-operative day, blood was simultaneously drawn from the portal and hepatic veins over a 2-h feeding period. The position of the hepatic vein cannula was verified using a tritiated water washout technique. In separate experiments, 200 microCi of [3-3H]glucose was added to the food in order to determine the relative contribution of D-glucose and 3-C precursors to newly synthesized glycogen. The 22-h fasting plasma portal vein concentrations of D-glucose, L-lactate, and L-alanine were 4.8 +/- 0.03, 0.81 +/- 0.06, and 0.20 +/- 0.03 mM, respectively (n = 5). The fasting hepatic vein plasma concentrations were 5.1 +/- 0.2, 0.70 +/- 0.15 and 0.19 +/- 0.03 mM, respectively. The portal-hepatic vein gradients after 22 h were -0.24, +0.16, and +0.01 mM for D-glucose, L-lactate, and L-alanine, respectively. At 20 min after beginning the meal, the respective gradients were +2.2, +0.53, and +0.44 mM, indicating hepatic uptake of all glycogen precursors. Of the total carbon from the three major precursors entering the liver as C-6, D-glucose contributed 82%, while alanine and lactate contributed 18% at 20 min. As portal vein D-glucose and L-alanine levels exceeded 6.65 +/- 0.69 and 0.32 +/- 0.07 mM, respectively, the portal-hepatic venous gradient became positive and increased linearly with portal concentrations. The glycogen concentration in the liver increased from a 22-h fast value of 5 mumol of glucosyl units/g wet weight to 101 +/- 7 mumol/g 2 h after the meal. The mean specific activity of portal vein plasma of [3-3H]glucose was 11,490 +/- 1,180 dpm/mumol (+/- S.E.) and that in the glycogen isolated from liver was 8,175 +/- 785 dpm/mumol of glycosyl units 2 h after the meal. The specific activity of liver [3H]glycogen relative to glucose after the meal was 0.73 +/- 0.08. It was concluded that a minimum of 73% of the newly synthesized glycogen was formed from the uptake and direct phosphorylation of portal blood D-glucose by the liver without prior conversion of glucose to 3-C units.
Laboratory of Metabolism, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland 20852.
G P
GP
Dobson
R L
RL
Veech
J V
JV
Passonneau
M T
MT
Huang
D000409:Alanine / Q000378:metabolism; D000641:Ammonia / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006503:Hepatic Veins / Q000502:physiology*; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008102:Liver Circulation; D008112:Liver Glycogen / Q000096:biosynthesis*; D008297:Male; D011169:Portal Vein / Q000502:physiology*; D011773:Pyruvates / Q000378:metabolism; D011865:Radioisotope Dilution Technique; D051381:Rats; D011919:Rats, Inbred Strains; D014316:Tritium
D001786:Blood Glucose; D007773:Lactates; D008112:Liver Glycogen; D011773:Pyruvates; D014316:Tritium; D000641:Ammonia; D005947:Glucose; D000409:Alanine