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Abstract
To determine whether the source of carbon for the indirect pathway of hepatic glycogen synthesis differs between the periportal and pericentral zones, we studied seven 24-h-fasted conscious rats given a constant 2-h intraduodenal infusion of glucose, 40% labeled with [U-13C]glucose (99% 13C enriched), to raise and maintain plasma glucose concentration at approximately 10 mM. Glycogen, glutamate, aspartate, and alanine were selectively sampled from the periportal and pericentral zones of the liver by the dual-digitonin pulse technique and analyzed by 13C-NMR for positional isotopomer distribution and by gas chromatography-mass spectrometry for mass isotopomer distribution. Plasma glucose mass isotopomer distribution was determined from gas chromatography-mass spectrometry. The isotopomer distribution indicates that there was no significant difference between the zones with respect to 1) percent direct flux of glucose into the glycogen (periportal, 34 +/- 4; pericentral, 38 +/- 4), 2) extent of oxaloacetate/fumarate equilibration (periportal, 0.54 +/- .01;, pericentral, 0.53 +/- 0.01), 3) dilution of tracer in oxaloacetate (periportal, 0.64 +/- 0.07;, pericentral, 0.64 +/- 0.07), or 4) inflow of pyruvate versus tricarboxylic acid cycle flux (periportal, 0.70 +/- 0.20; pericentral, 0.68 +/- 0.16). Positional isotopomer populations, determined from the 13C-13C splitting in C3 and C4 of periportal and pericentral glycogen, were indistinguishable, indicating no significant differences in the source of the 3-carbon precursors for hepatic glycogen synthesis by the indirect pathway. In conclusion, glucose metabolism is the same in the periportal and pericentral zones with regard to 1) the relative flux of carbon via the direct/indirect pathways, 2) the source of the 3-carbon precursor used in the indirect pathway of glycogen synthesis, and 3) the flux of the 3-carbon precursors through the tricarboxylic acid cycle.
Highlights
Proposed that hepatocytes in the periportal zone are gluconeogenic and that pericentral hepatocytes are glycolytic [3]
Even though the relative contributions for the direct and indirect pathway were similar between the two populations of hepatocytes, it is still possible that the three carbon units for the indirect pathway of glycogen synthesis in one population of hepatocytes was derived by intracellular glycolysis while the other population of hepatocytes derive their three carbon units for glycogenesis from extrahepatic sources
This question carries additional weight in view of our recent study in awake triple-catheterized dogs, in which we found that during an intraduodenal glucose infusion net hepatic glucose uptake could account for all of the glycogen synthesized by the liver from both the direct and indirect pathways [6]
Summary
Proposed that hepatocytes in the periportal zone are gluconeogenic and that pericentral hepatocytes are glycolytic [3]. The data derived from the 13C–13C J coupling between the C3 and C4 carbons of glycogen is unique in that the 13C–13C splitting pattern will be very different if the source of the three carbon units for the indirect pathway is derived from intracellular glycolysis versus extrahepatic sources since the C3 and C4 carbons reflect the contribution from two different pyruvate molecules This type of positional isotopomer analysis is unique and the most comprehensive way of addressing this question since it reflects the 13C labeling in adjacent carbons within the same glucose molecule as opposed to examining the 13C labeling distribution within a population of glucose molecules. This type of analysis was not possible in our previous study since only [1-13C]glucose was used and does not lead to a comparable array of isotopomeric species, which provide a richer wealth of informational content
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