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

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

scholarly journals The role of insulin in the modulation of glucagon-dependent control of phenylalanine hydroxylation in isolated liver cells

1987 ◽  
Vol 242 (3) ◽  
pp. 655-660 ◽  
Author(s):  
M J Fisher ◽  
A J Dickson ◽  
C I Pogson
Keyword(s):  
Cyclic Amp ◽  
Insulin Action ◽  
Phenylalanine Hydroxylase ◽  
Liver Cells ◽  
Phosphorylation State ◽  
Isolated Liver Cells ◽  
The Impact ◽  
Isolated Liver ◽  
Stimulation Of

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.

scholarly journals 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

1992 ◽  
Vol 284 (3) ◽  
pp. 761-766 ◽  
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.

scholarly journals The polyamine-dependent modulation of phenylalanine hydroxylase phosphorylation state and enzymic activity in isolated liver cells

1986 ◽  
Vol 237 (1) ◽  
pp. 277-279 ◽  
Author(s):  
M J Fisher ◽  
A J Dickson ◽  
C I Pogson
Keyword(s):  
Protein Phosphatase ◽  
Phenylalanine Hydroxylase ◽  
Liver Cells ◽  
Enzymic Activity ◽  
Phosphorylation State ◽  
Isolated Liver Cells ◽  
Phosphatase 2A ◽  
Pre Treatment ◽  
Isolated Liver

The role of polyamines in the control of phenylalanine hydroxylase phosphorylation state and enzymic activity was investigated. Pre-treatment of liver cells with spermine (1 mM) abolishes the glucagon (1 nM)-stimulated increase in hydroxylase phosphorylation. Concurrently there is a decrease in phenylalanine hydroxylation flux, reflecting decreased enzyme activity; 50% inhibition occurs at approx. 10 microM-spermine. These results are discussed in the context of reports concerning the properties of protein phosphatase 2A.

scholarly journals The effect of experimental diabetes on phenylalanine metabolism in isolated liver cells

1985 ◽  
Vol 227 (1) ◽  
pp. 169-175 ◽  
Author(s):  
M A Santana ◽  
M J Fisher ◽  
A J Bate ◽  
C I Pogson
Keyword(s):  
Enzyme Activity ◽  
Hormonal Regulation ◽  
Metabolic Flux ◽  
Phenylalanine Hydroxylase ◽  
Experimental Diabetes ◽  
Liver Cells ◽  
Enzyme Protein ◽  
Isolated Liver Cells ◽  
Phenylalanine Metabolism ◽  
Isolated Liver

Chronic (10-day) diabetes was associated with increased metabolic flux through phenylalanine hydroxylase in isolated liver cells. This flux was stimulated by 0.1 microM-glucagon, but not by 10 microM-noradrenaline; 0.1 microM-insulin affected neither basal nor glucagon-stimulated flux. The increased rate of phenylalanine hydroxylation in diabetes was accompanied by parallel increases in enzyme activity (as measured with artificial cofactor) and immunoreactive-enzyme-protein content. In contrast with total protein synthesis, which decreased, phenylalanine hydroxylase synthesis persisted at the control rate in cells from diabetic animals. These findings are discussed in relation to the hormonal regulation of the hydroxylase and the known metabolic consequences of chronic diabetes.

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

1998 ◽  
Vol 331 (1) ◽  
pp. 89-97 ◽  
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.

scholarly journals Arachidonic acid synthesis studied in isolated liver cells

FEBS Letters ◽  
1981 ◽  
Vol 133 (2) ◽  
pp. 201-204 ◽  
Author(s):  
B.O. Christophersen ◽  
Jon Norseth
Keyword(s):  
Arachidonic Acid ◽  
Acid Synthesis ◽  
Liver Cells ◽  
Isolated Liver Cells ◽  
Isolated Liver

Decreased glucagon-stimulated cyclic AMP production by isolated liver cells of rats with type 2 diabetes

1983 ◽  
Vol 32 (1) ◽  
pp. 13-26 ◽  
Author(s):  
Bernard Portha ◽  
Hilda Chamras ◽  
Yvonne Broer ◽  
Luc Picon ◽  
Gabriel Rosselin
Keyword(s):  
Type 2 Diabetes ◽  
Cyclic Amp ◽  
Liver Cells ◽  
Isolated Liver Cells ◽  
Isolated Liver
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