Parathyroid hormone stimulation of glucose and urea production in isolated liver cells

The stimulation of phenylalanine hydroxylation in isolated liver cells by sub-maximally effective concentrations of glucagon (less than 0.1 microM) is antagonized by insulin (0.1 nM-0.1 microM). This phenomenon is a consequence of a decrease in the glucagon-stimulated phosphorylation of phenylalanine hydroxylase from liver cells incubated in the presence of insulin. The impact of insulin on the phosphorylation state and activity of the hydroxylase is mimicked by incubation of liver cells in the presence of orthovanadate (10 microM). A series of cyclic AMP and cyclic GMP analogues enhanced phenylalanine hydroxylation: in each case insulin diminished the stimulation of flux. These results are discussed in the light of the characteristics of insulin action on other metabolic processes.

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Effect of treatment in vivo of rats with bacterial endotoxin on fructose 2,6-bisphosphate metabolism and L-pyruvate kinase activity and flux in isolated liver cells

Biochemical Journal ◽

10.1042/bj2840761 ◽

1992 ◽

Vol 284 (3) ◽

pp. 761-766 ◽

Cited By ~ 14

Author(s):

E D Ceppi ◽

R G Knowles ◽

K M Carpenter ◽

M A Titheradge

Keyword(s):

Pyruvate Kinase ◽

Intact Cell ◽

Total Activity ◽

Liver Cells ◽

Bacterial Endotoxin ◽

Phosphorylation State ◽

Isolated Liver Cells ◽

Effect Of Treatment ◽

Isolated Liver ◽

Stimulation Of

The effect of treatment of rats with bacterial endotoxin on fructose 2,6-bisphosphate (Fru-2,6-P2) metabolism was investigated in isolated liver cells prepared from 18 h-starved animals. The results obtained support the hypothesis that a stimulation of 6-phosphofructo-1-kinase (PFK-1) activity and an inhibition of fructose-1,6-bisphosphatase (Fru-1,6-P2ase) may be one mechanism underlying the inhibition of gluconeogenesis from lactate and pyruvate by endotoxin. We suggest that the stimulation of PFK-1 and inhibition of Fru-1,6-P2ase activity is the result of a 2-3-fold increase in Fru-2,6-P2. The latter is not due to changes in the total activity or phosphorylation state of the bifunctional 6-phosphofructo-2-kinase (PFK-2)/fructose-2,6-bisphosphatase, but appears to be the result of a decrease in the cytosolic concentration of phosphoenolpyruvate (PEP), an inhibitor of PFK-2 activity. The effect of endotoxin is resistant to the presence of glucagon, which has comparable effects in cells prepared from both control and endotoxin-treated animals. The mechanism by which endotoxin treatment of the rat decreases PEP and gluconeogenesis remains to be established. However, it does not involve alterations in either the total activity or the phosphorylation state of pyruvate kinase, nor does it involve increased flux through this enzyme in the intact cell, which is in fact decreased in this model of septic shock. It is suggested that the decreased flux may result from a lower rate of formation of PEP, suggesting that the prime lesion in sepsis is an inhibition of one or more of the steps leading to PEP formation.

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Effect of ornithine and lactate on urea synthesis in isolated hepatocytes

Biochemical Journal ◽

10.1042/bj1600205 ◽

1976 ◽

Vol 160 (2) ◽

pp. 205-209 ◽

Cited By ~ 35

Author(s):

S Briggs ◽

R A Freedland

Keyword(s):

Lactate Concentration ◽

Isolated Hepatocytes ◽

Liver Cells ◽

Urea Synthesis ◽

Isolated Liver Cells ◽

Urea Production ◽

Relationship Of ◽

The Relationship ◽

Isolated Liver

1. In hepatocytes isolated from 24 h-starved rats, urea production from ammonia was stimulated by addition of lactate, in both the presence and the absence of ornithine. The relationship of lactate concentration to the rate of urea synthesis was hyperbolic. 2. Other glucose precursors also stimulated urea production to varying degrees, but none more than lactate. Added oleate and butyrate did not stimulate urea synthesis. 3. Citrulline accumulation was largely dependent on ornithine concentration. As ornithine was increased from 0 to 40 mM, the rate of citrulline accumulation increased hyperbolically, and was half-maximal when ornithine was 8-12 mM. 4. The rate of citrulline accumulation was independent of the presence of lactate, but with pyruvate the rate increased. 5. The rate of urea production continued to increase as ornithine was varied from 0 to 40 mM. 6. It was concluded that intermediates provided by both ornithine and lactate are limiting for urea production from ammonia in isolated liver cells. It was suggested that the stimulatory effect of lactate lies in increased availability of cytosolic aspartate for condensation with citrulline.

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Insulin antagonizes the glucagon-mediated stimulation of phenylalanine hydroxylase activity in isolated liver cells

Biochemical Society Transactions ◽

10.1042/bst0140310 ◽

1986 ◽

Vol 14 (2) ◽

pp. 310-311

Author(s):

MICHAEL J. FISHER ◽

ALAN J. DICKSON ◽

CHRISTOPHER I. POGSON

Keyword(s):

Phenylalanine Hydroxylase ◽

Liver Cells ◽

Hydroxylase Activity ◽

Isolated Liver Cells ◽

Isolated Liver ◽

Stimulation Of

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3,5,3′-Tri-iodo-l-thyronine acutely regulates a protein kinase C-sensitive, Ca2+-independent, branch of the hepatic α1-adrenoreceptor signalling pathway

Biochemical Journal ◽

10.1042/bj3310089 ◽

1998 ◽

Vol 331 (1) ◽

pp. 89-97 ◽

Cited By ~ 2

Author(s):

Francisco J. DAZA ◽

Roberto PARRILLA ◽

Angeles MARTÍN-REQUERO

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Hepatic Metabolism ◽

Liver Cells ◽

Signalling Pathway ◽

Perfused Liver ◽

Kinase C ◽

Isolated Liver Cells ◽

Isolated Liver ◽

Stimulation Of

This work aimed to investigate the acute effect of the thyroid hormone 3,5,3´-tri-iodo-l-thyronine (T3) in regulating the hepatic metabolism either directly or by controlling the responsiveness to Ca2+-mobilizing agonists. We did not detect any acute metabolic effect of T3 either in perfused liver or in isolated liver cells. However, T3 exerted a powerful inhibitory effect on the α1-adrenoreceptor-mediated responses. The promptness of this T3 effect rules out that it was the result of rate changes in gene(s) transcription. T3 inhibited the α1-adrenoreceptor-mediated sustained stimulation of respiration and release of Ca2+ and H+, but not the glycogenolytic or gluconeogenic responses, in perfused liver. In isolated liver cells, T3 enhanced the α1-agonist-induced increase in cytosolic free Ca2+ and impeded the intracellular alkalinization. Since T3 also prevented the α1-adrenoreceptor-mediated activation of protein kinase C, its effects on pH seem to be the result of a lack of activation of the Na+/H+ exchanger. The failure of T3 to prevent the α1-adrenergic stimulation of gluconeogenesis despite the inhibition of protein kinase C activation indicates that the elevation of cytosolic free Ca2+ is a sufficient signal to elicit that response. T3 also impaired some of the angiotensin-II-mediated responses, but did not alter the effects of PMA on hepatic metabolism, indicating, therefore, that some postreceptor event is the target for T3 actions. The differential effect of T3 in enhancing the α1-adrenoreceptor-mediated increase in cytosolic free Ca2+ and preventing the activation of protein kinase C, provides a unique tool for further investigating the role of each branch of the signalling pathway in controlling the hepatic functions. Moreover, the low effective concentrations of T3 (⩽ 10 nM) in perturbing the α1-adrenoreceptor-mediated response suggests its physiological significance.

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