Gluconeogenesis and Related Aspects of Glycolysis

Hers, Henri‐Géry; Hue, Louis

doi:10.1146/annurev.bi.52.070183.003153

Cited by 515 publications

(270 citation statements)

References 132 publications

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“…furthermore, demonstrable in the absence of-added substrate (data not shown), indicating to be essentially indcpendent of hormonally stimulated gluconeogenic and inhibited glycolytic flux (for review see [37] diminished by increasing the external phosphate concentration. Thus, it appears reasonable to assume that glucagon decreases phosphate release from the hepatocytes.…”

Section: Culculutionsmentioning

confidence: 90%

Possible role of Pi supply in mitochondrial actions of glucagon

et al. 1984

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Glucagon is able to diminish the net release of inorganic phosphate (Pi) occurring on incubation of isolated hepatocytes from 48-h-starved rats. Concomitantly the hormone increases the cellular Pi content. This is associated with a rise of Pi in the cytosolic fraction. Other hormonal effectors like phenylephrine, vasopressin and angiotensin I1 exert a smaller and transient effect as compared to glucagon. It is proposed that this increase in Pi availability to the mitochondria, by favouring substratc lcvcl phosphorylation at the succinyl-CoA synthetasc step plays a role in the development of the metabolite pattern found in the mitochondrial matrix spacc after exposure of hepatocytes to glucagon or the above agents. With regard to the glutamate level this view is evidcnced by the finding that its hormone-dependent decrease was inversely correlated to the respective increase in the cytosolic Pi concentration. Further evidence is provided by experiments with isolated mitochondria incubatcd under state-3 conditions at medium Pi concentrations corresponding to those metabolically active in the cytosolic compartment of control and glucagon-stiinulatcd hepatocytes, being 2 mM and 3 mM, respectively. Increasing medium phosphate concentration from 2 mM to 3 mM caused a marked decrease in the levcl of succinyl-CoA and increased the rates of 2-oxoglutarate utilization and of malate and phosphoenolpyruvate production. Citrulline synthesis also was found to be stimulated at 3 tnM Pi. Taken together our results suggest a rolc of Pi supply in mitochondrial actions of glucagon in intact hepatocytes. Moreover, they could contribute to a bcttcr interpretation of glucagon effects on isolated mitochondria from hormone-pretreated liver cells.The effects of glucagon on liver mitochondria may be divided into two groups: the first one comprising the changes occurring in the mitochondrial compartment of intact hepatocytes [l] as revealed by the digitonin fractionation technique [2] and the second one consisting of the effects demonstrable after isolation of the mitochondria from glucagon-stimulated hepatocytes. With respect to the first group the drop in glutamate and 2-oxoglutarate as well as thc increase in the ATP, phosphoenolpyruvate and acetyl-CoA contents [l] are noteworthy. As to the second group about 15 different parameters have been described out of which the apparent stimulation of respiration (for review scc [3]) and the activation of pyruvate carboxylase and citrullinc formation [9,181 have been extensively investigated. The results have been interpreted as to indicate that the isolated mitochondria represent a valid model for the hormone's action on mitochondrial metabolism in intact hepatocytes. Howcver, evidence has been presented for the fact that a number of the hormone effects demonsti-ablc with the isolated mitochondria strongly depend on the conditions of mitochondria isolation, storage and incubation [I 91. In the course of studies on the influence of various isolation media on the preservation of functional in...

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Section: Culculutionsmentioning

confidence: 90%

Possible role of Pi supply in mitochondrial actions of glucagon

et al. 1984

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“…It is therefore not surprising that these key enzymes are the main targets of regulatory mechanisms. Short-term regulation involves both the supply of glycolytic or gluconeogenic substrates and the control of the catalytic properties of the enzymes through allosteric changes and phosphorylation [1,2]. Long-term regulation in liver involves changes in gene expression and protein synthesis [3,4] and is the subject of the present review.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional control of genes that regulate glycolysis and gluconeogenesis in adult liver

Lemaigre¹,

Rousseau²

1994

Biochemical Journal

100

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“…The hepatic gluconeogenicaglycolytic pathway is regulated by allosteric modulators, and phosphorylationadephosphorylation and control of gene expression of several regulatory enzymes. 7,8 These enzymes control hepatic glucose production and utilization through regulation of three major substrate cycles: glucoseaglucose 6-phosphate, fructose 6-phosphatea fructose-1,6-bisphosphate and phosphoenolpyruvatea pyruvate. The fructose 6-phosphateafructose-1,6-bisphosphate substrate cycle is also regulated by a subcycle in which the amount of the regulatory molecule fructose-2,6-bisphosphate (Fru-2,6-P 2 ) is controlled by the bifunctional enzyme 6-phospho-fructo-2-kinaseafructose-2,6-bisphosphatase (PFK-2a FBPase-2).…”

Section: Introductionmentioning

confidence: 99%

Effect of starvation on gene expression of regulatory enzymes of glycolysis/gluconeogenesis in genetically obese (fa/fa) Zucker rats

et al. 1998

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OBJECTIVE: To study the mechanism that controls fructose-2,6-bisphosphate (Fru-2,6-P 2 ) accumulation, as well as the mRNAs levels of the glycolyticagluconeogenic regulatory enzymes in the livers of fed and starved lean ( faa-) and obese ( faafa) Zucker rats. DESIGN: Rats were fed a standard chow or deprived of food for 24 h. SUBJECTS: Male lean (faa-) and genetically obese ( faafa) rats (nine weeks old). MEASUREMENTS: Fru-2,6-P 2 concentration, 6-phosphofructo-2-kinase (PFK-2), glucokinase (GK), pyruvate kinase (PK) activities and the mRNA levels of GK, PFK-2, L-type pyruvate kinase, fructose-1,6-bisphosphatase (FBPase-1) and phosphoenolpyruvate carboxykinase (PEPCK) were analyzed. RESULTS: PFK-2aFBPase-2 mRNA decreased during starvation in both faa-and faafa animals. Although PFK2aFBPase-2 mRNA levels were similar in fed lean and obese rats, PFK-2 concentration and activity were higher in fed obese than in fed lean animals, which might explain the high concentration of Fru-2,6-P 2 observed in obese animals. During starvation, PFK-2 protein concentration decreased, correlating with the enzymatic activity and Fru-2,6-P 2 levels. The activities of GK and L-pyruvate kinase (L-PK) also increased in fed obese (faafa) rats compared with fed lean (faa-) animals, but decreased during starvation. The mRNA levels of glycolytic enzymes in fed obese rats were similar (PFK-2) or higher than (GK, L-PK) in fed lean animals. During starvation, they decreased in lean and obese rats with one important exception, GK mRNA remained high in obese animals. The mRNA of gluconeogenic enzymes remained constant (FBPase-1) or increased (PEPCK) during fasting. CONCLUSION: The changes observed might be explained by the hyperinsulinaemia observed in the liver of obese rats, which might lead to the stimulation of glycolysis and lipogenesis.

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Gluconeogenesis and Related Aspects of Glycolysis

Cited by 515 publications

References 132 publications

Possible role of Pi supply in mitochondrial actions of glucagon

Possible role of Pi supply in mitochondrial actions of glucagon

Transcriptional control of genes that regulate glycolysis and gluconeogenesis in adult liver

Effect of starvation on gene expression of regulatory enzymes of glycolysis/gluconeogenesis in genetically obese (fa/fa) Zucker rats

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