Gluconeogenesis predominates in periportal regions of the liver lobule

Matsumura, Tae; Kashiwagi, Toru; Meren, Haruya; Thurman, Ronald G.

doi:10.1111/j.1432-1033.1984.tb08480.x

Cited by 48 publications

(18 citation statements)

References 33 publications

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“…In marked contrast to the data obtained from perfusion in the anterograde direction, the decrease in oxygen concentration was much greater in the periportal than in peri venous regions when perfusion was in the [68], Miniature oxygen electrodes have also been employed in studies of glycolysis [65] and gluconeogenesis [66] in different regions of the liver lobule using both stopped-flow and kinetic analysis. The hypothesis that gly colysis occurs at different rates in various zones was evaluated by studying the effect of ethanol and glucose infusion on regional rates of oxygen uptake.…”

Section: Fluxes In Vitro Studied With Noninvasive Techniques Local Ramentioning

confidence: 99%

“…Rates of gluconeo genesis were quantified in periportal and perivenous regions by monitoring the extra oxygen taken up locally following the addi tion of a glucogenic precursor, lactate. These studies indicated that glycolysis [65] and glu coneogenesis [66] predominate in perive nous and periportal regions of the liver lo bule, respectively.…”

Section: Fluxes In Vitro Studied With Noninvasive Techniques Local Ramentioning

confidence: 99%

“…Rates of gluconeogenesis from lactate were calculated in periportal and perivenous regions of the liver lobule in perfused rat livers from in creases in oxygen uptake due to lactate [66]. When lactate (0.1-2.0 mmol/1) was infused into livers from fasted rats perfused in either the anterograde or retrograde direction, a good correlation (r = 0.97) between rates of glucose production and extra oxygen uptake was observed as expected.…”

Section: Fluxes In Vitro Studied With Noninvasive Techniques Local Ramentioning

confidence: 99%

“…(3) Oxygen uptake under stopped-flow conditions may be the result of both metabolic consumption and loss or gain by diffusion. In the upstream area oxygen is lost due to reduction to water and to diffu sion to the downstream area, where oxygen well established, rates of glucose production in periportal and perivenous regions of the liver lobule were calculated from local changes in rates of oxygen uptake for the first time [66], Gluconeogenesis was half-maximal in both regions of the liver lobule in the pres ence or absence of epinephrine with 0.4-0.5 mmol/1 lactate. Maximal rates of glucose production were 60 ± 7 and 25 ± 4 pmol/ g/h in periportal and perivenous regions of the liver lobule, respectively, in the presence of saturating concentrations of lactate (2 mmol/1).…”

Section: Differences Of Opinion In the Interpretation Of Studies Withmentioning

confidence: 99%

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Hepatocyte Heterogeneity in the Metabolism of Carbohydrates

Jungermann

Thurman²

1992

Enzyme

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109

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Periportal and perivenous hepatocytes possess different amounts and activities of the rate-generating enzymes of carbohydrate and oxidative energy metabolism and thus different metabolic capacities. This is the basis of the model of metabolic zonation, according to which periportal cells catalyze predominantly the oxidative catabolism of fatty and amino acids as well as glucose release and glycogen formation via gluconeogenesis, and perivenous cells carry out preferentially glucose uptake for glycogen synthesis and glycolysis coupled to liponeogenesis. The input of humoral and nervous signals into the periportal and perivenous zones is different; gradients of oxygen, substrates and products, hormones and mediators and nerve densities exist which are important not only for the short-term regulation of carbohydrate metabolism but also for the long-term regulation of zonal gene expression. The specialization of periportal and perivenous hepatocytes in carbohydrate metabolism has been well characterized. In vivo evidence is provided by the complex metabolic situation termed the ‘glucose paradox’ and by zonal flux differences calculated on the basis of the distribution of enzymes and metabolites. In vitro evidence is given by the different flux rates determined with classical invasive techniques, e.g. in periportal-like and perivenouslike hepatocytes in cell culture, in periportal- and perivenous-enriched hepatocyte populations and in perfused livers during orthograde and retrograde flow, as well as with noninvasive techniques using miniature oxygen electrodes, e.g. in livers perfused in either direction. Differences of opinion in the interpretation of studies with invasive and noninvasive techniques by the authors are discussed. The declining gradient in oxygen concentrations, the decreasing glucagon/insulin ratio and the different innervation could be important factors in the zonal expression of the genes of carbohydrate-metabolizing enzymes. While it is clear that the hepatocytes sense the glucagon/insulin gradients via the respective hormone receptors, it is not known how they sense different oxygen tensions; the O(2) sensor may be an oxygen-binding heme protein. The zonal separation of glucose release and uptake appears to be important for the liver to operate as a ‘glucostat’. Thus, zonation of carbohydrate metabolism develops gradually during the first weeks of life, in part before and in part with weaning, when (in rat and mouse) the fat- and protein-rich but carbohydrate-poor nutrition via milk is replaced by carbohydrate-rich food. Similarly, zonation of carbohydrate metabolism adapts to longer lasting alterations in the need of a ‘glucostat’, such as starvation, diabetes, portocaval anastomoses or partial hepatectomy.

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Section: Fluxes In Vitro Studied With Noninvasive Techniques Local Ramentioning

confidence: 99%

Section: Fluxes In Vitro Studied With Noninvasive Techniques Local Ramentioning

confidence: 99%

Section: Fluxes In Vitro Studied With Noninvasive Techniques Local Ramentioning

confidence: 99%

Section: Differences Of Opinion In the Interpretation Of Studies Withmentioning

confidence: 99%

See 2 more Smart Citations

Hepatocyte Heterogeneity in the Metabolism of Carbohydrates

Jungermann

Thurman²

1992

Enzyme

Self Cite

109

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“…The model of metabolic zonation of the liver parenchyma was originally based on the heterotopic distribution of enzyme [6,7,211. However, these measurements are indirect and restricted to few metabolic processes.…”

Section: Metabolic Sign Ficance Of the Heterogeneitymentioning

confidence: 99%

Zonal distribution of fatty acid synthase in liver parenchyma of male and female rats

Katz¹,

Thiele²,

Giffhorn-Katz³

1989

European Journal of Biochemistry

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1. A sensitive radiochemical assay was established to determine the activity of fatty acid synthase in microdissected liver tissue of less than 1 pg dry mass.2. In female rats, the enzyme activity in perivenous tissue was twice that in periportal liver tissue while it was homogeneously distributed in livers of male animals. The overall activity was higher in female than in male animals.3. The absolute activity, as well as the perivenous/periportal ratio, was reduced during starvation and in diabetes. They were greatly increased after refeeding to values above those observed in animals during normal feeding.4. Ovarectomy or administration of testosterone to female rats resulted in a significant reduction of the zonal heterogeneity.5. Castration or administration of estradiol to male animals was followed by an increase in the enzyme activity exclusively in the perivenous tissue, resulting in a zonal heterogeneity as observed in female rats.Periportal and perivenous hepatocytes exhibit different metabolic capacities : enzyme activities involved in gluconeogenesis, urea synthesis from amino acids and bile formation are higher in the periportal zone of the rat liver acinus; enzyme activities involved in glycolysis and biotransformation are higher in the perivenous zone [I -41. Therefore, it was postulated that periportal hepatocytes catalyze net glucose formation from lactate and alanine and perivenous hepatocytes catalyze net glucose degradation.This hypothesis was confirmed by calculation of metabolic flux rates in the different zones of the acinus [ S ] as well as by measurement of the zonal metabolic activities in isolated perfused livers using miniature oxygen electrodes [6, 71 or histochemical techniques [8, 91. Glycolysis and oxidative decarboxylation of pyruvate supply acetyl-CoA, which serves as a substrate for the synthesis of fatty acids during carbohydrate feeding of rats. Thus, the localization of the liponeogenic key enzymes, ATP citrate lyase [lo] and acetyl-CoA carboxylase [ll], predominantly in the perivenous zone supports the concept of the metabolic zonation in liver. A similar zonal distribution was described in female rats for glucose-6-phosphate dehydrogenase [12, 131 and for the 'malic' enzyme [13, 141, which supply NADPH for fatty acid synthesis and hydroxylation reactions.The zonal distribution of fatty acid synthase, the third classical enzyme of liponeogenesis, is demonstrated in the Correspondence to N. Katz,

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Bivascular liver perfusion in the anterograde and retrograde modes: Zonation of the response to inhibitors of oxidative phosphorylation

Constantin

Ishii–Iwamoto

Suzuki‐Kemmelmeier

et al. 1995

Cell Biochemistry & Function

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The action of cyanide (500 microM), 2,4-dinitrophenol (50 microM) and atractyloside (100 microM) on glycogen catabolism and oxygen uptake was investigated in the bivascularly perfused liver of fed rats. Cyanide, 2,4-dinitrophenol and attractyloside were infused at identical rates into the hepatic artery in either the anterograde or retrograde perfusion. The accessible aqueous cell spaces were determined by means of the multiple-indicator dilution technique. Glucose release, oxygen uptake and glycolysis were measured as metabolic parameters. Oxygen uptake changes per unit cell space caused by atractyloside (inhibition) and 2,4-dinitrophenol (stimulation) were equal in the retrograde perfusion (periportal cells) and the anterograde perfusion (space enriched in perivenous cells); the decreases caused by cyanide were higher in the retrograde perfusion. Glucose release from periportal cells was not increased upon inhibition of oxidative phosphorylation, a phenomenon which was independent of the mechanism of action of the inhibitor. There were nearly identical changes in glycolysis in the periportal and perivenous cells. It was concluded that: (1) oxygen concentration in the perfused rat liver, if maintained above 100 microM, had little influence on the zonation of the respiratory activity; (2) in spite of the lower activities of the key enzymes of glycolysis in the periportal hepatocytes, as assayed under standard conditions, these cells were as effective as the perivenous ones in generating ATP in the cytosol when oxidative phosphorylation was impaired; (3) the key enzymes of glycogenolysis and glycolysis in periportal and perivenous cells responded differently to changes in the energy charge.

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Gluconeogenesis predominates in periportal regions of the liver lobule

Cited by 48 publications

References 33 publications

Hepatocyte Heterogeneity in the Metabolism of Carbohydrates

Hepatocyte Heterogeneity in the Metabolism of Carbohydrates

Zonal distribution of fatty acid synthase in liver parenchyma of male and female rats

Bivascular liver perfusion in the anterograde and retrograde modes: Zonation of the response to inhibitors of oxidative phosphorylation

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