Regionality of glucose-6-phosphate hydrolysis in the liver lobule of the rat: Metabolic heterogeneity of “portal” and “septal” sinusoids

Abstract

To investigate intercellular compartmentation of liver metabolism, we have recently introduced new procedures for quantitative assessment of metabolic liver cell heterogeneity both along sinusoids of portal and septal origins as well as at the level of the parenchymal unit, and also for three-dimensional imaging of enzyme and metabolite distribution. As part of the evaluation of the role of metabolic liver cell heterogeneity for the regulation of net substrate flux in the glucose-6-phosphatase/glucokinase system, and for the reduction of of these antagonistic enzymes, these techniques were used on livers from male rats. They served to obtain distribution data on glucose-6-phosphatase (the hydrolytic component of the glucose-6-phosphatase/glucokinase system) and its substrate, glucose-6-P, during the postresorptive phase (i.e., a metabolic state of net glucose release). Glucose-6-phosphatase (Vmax) and glucose-6-P were shown to decrease along the sinusoidal axis, and values of both parameters were significantly higher along sinusoids of portal than septal origin. Distribution of in vivo rates of glucose-6-P hydrolysis indicates the importance of metabolite distribution for in vivo regulation of liver cell function, insofar as it considerably increases the degree of heterogeneity among hepatocytes over that maximal rates of glucose formation. Histo- and microchemical data support the concept of a "lobular parenchymal unit" composed of "primary lobules," and justify the conclusion that hepatocyte function, in addition to the hormonal and nutritional states of the animal, not only depends upon cell location along the sinusoidal axis, but also on the origin of sinusoids.

Microanatomy of the human liver—exploring the hidden interfaces

“…However, it does not explain lateral or portal-portal gradients between adjacent portal tracts as seen in animals and in humans. [8][9][10][11][12] The classic lobule is not the smallest functional unit but rather a composite of many smaller units, with the acinus as one conceptual candidate.…”

“…These sinusoids are referred to as ''portal'' sinusoids in rat livers. 9 In contrast, the septal zone is fed by inlet venules from the distal part of the portal venule. Sinusoids arising in this region, called the ''septal'' sinusoids in the rat liver, 9 do not have a transverse course, but immediately head radially towards the central vein.…”

The portal lobule in rat liver fibrosis: A re-evaluation of the liver unit

“…An important point of this concept is to consider that zone 3, with the worst portal blood supply, surround CVs and extend to interlobular portal veins from which TPBs arise. The concept of the liver acinus has become the most accepted description during the past 40 years and is thought to explain many pathologic lesions of the liver; however, in recent years several studies on liver lobular angioarchitectures [15][16] and enzyme distributions, [17][18][19] both of which reflect the microcirculation, provide contradictions to the acinus concept.…”

Revelation of simple and complex liver acini after portal transplantation of pancreatic islets or thyroid follicles in rats

“…(2) Studies that investigated a peculiar metabolic function of hepatocytes organized in a specific manner within the parenchyma. The hepatic unit organization is then evaluated as a consequence of the distribution pattern of this function, such as the activity of a certain enzyme, 10,11,25,26 or, among others, the selectivity of cell permeabilization following digitonin-pulse perfusion of the liver 27 or colloidal gold uptake. 28 These studies yielded interesting but very contradictory data, and none was able to visualize Rappaport's liver acinus.…”