Following the pioneering experiments in the mid-nineteenth century of Claude Bernard, it was fairly well established that dietary glucose in the post-prandial state was taken up directly by the liver and incorporated into newly synthesized glycogen. About 10 years ago this viewpoint was strongly contested by the radiotracer studies of Newgard et al., (JBC 1984;258:8046-52), later to be supported by Drs. J. Katz and B. Landau. Their position was that the metabolic fate of dietary glucose was not the direct incorporation into liver glycogen, but rather it was first broken down to C3 units by unspecified organs of the body which then returned to the liver to form glycogen via gluconeogenesis. This latter pathway was called the """"""""Indirect Pathway"""""""", and an entirely new field of inquiry termed """"""""The Glucose Paradox"""""""" was born. We challenged this interpretation and carried out experiments on chronically cannulated male Wistar rats which were fed ground chow for 2 hr for six days. On the 7th post-operative day, blood was simultaneously drawn from the portal and hepatic veins over a 2 hr feeding period. The position of the hepatic vein cannula was verified using a tritiated water washout technique. In separate experiments, 200 uCi 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. Our results demonstrate that 73% of newly synthesized liver glycogen formed during the 2 hr of feeding came directly from the uptake and phosphorylation of dietary glucose from the gut via the portal vein without prior conversion to 3-C precursors.
