scholarly journals The role of tryptophan 2,3-dioxygenase in the hormonal control of tryptophan metabolism in isolated rat liver cells. Effects of glucocorticoids and experimental diabetes

1985 ◽  
Vol 229 (2) ◽  
pp. 499-504 ◽  
Author(s):  
M Salter ◽  
C I Pogson
Keyword(s):  
Fold Increase ◽  
Maximal Activity ◽  
Kynurenine Pathway ◽  
Liver Cells ◽  
Diabetic Rats ◽  
Hormonal Control ◽  
Acetyl Coa ◽  
Dexamethasone Phosphate ◽  
Adrenalectomized Rats

The metabolism of L-tryptophan by isolated liver cells prepared from control, adrenalectomized, glucocorticoid-treated, acute-diabetic, chronic-diabetic and insulin-treated chronic-diabetic rats was studied. Liver cells from adrenalectomized rats metabolized tryptophan at rates comparable with the minimum diurnal rates of controls, but different from rates determined for cells from control rats 4h later. Administration of dexamethasone phosphate increased the activity of tryptophan 2,3-dioxygenase (EC 1.13.11.11) 7-8-fold, and the flux through the kynurenine pathway 3-4-fold, in cells from both control and adrenalectomized rats. Increases in flux through kynureninase (EC 3.7.1.3) and to acetyl-CoA can be explained in terms of increased substrate supply from tryptophan 2,3-dioxygenase. The metabolism of tryptophan was increased 3-fold in liver cells isolated from acutely (3 days) diabetic rats, with a 7-8-fold increase in the maximal activity of tryptophan 2,3-dioxygenase. The oxidation of tryptophan to CO2 and metabolites of the glutarate pathway increased 4-5-fold, consistent with an increase in picolinate carboxylase (EC 4.1.1.45) activity. Liver cells isolated from chronic (10 days) diabetic rats metabolized tryptophan at rates comparable with those of cells from acutely diabetic rats, but with a 50% decrease in the activity of tryptophan 2,3-dioxygenase. The proportion of flux from tryptophan 2,3-dioxygenase to acetyl-CoA, however, was increased by 50%; this was indicative of further increases in the activity of picolinate carboxylase. Administration of insulin partially reversed the effects of chronic diabetes on the activity of tryptophan 2,3-dioxygenase and flux through the kynurenine pathway, but had no effect on the increased activity of picolinate carboxylase. The role of tryptophan 2,3-dioxygenase in regulating the blood tryptophan concentration is discussed with reference to its sensitivity to the above conditions.

scholarly journals The metabolism of l-phenylalanine and l-tyrosine by liver cells isolated from adrenalectomized rats and from streptozotocin-diabetic rats

1985 ◽  
Vol 228 (1) ◽  
pp. 249-255 ◽  
Author(s):  
J C Stanley ◽  
M J Fisher ◽  
C I Pogson
Keyword(s):  
Insulin Treatment ◽  
Maximal Activity ◽  
Liver Cells ◽  
Diabetic Rats ◽  
Steroid Treatment ◽  
Phosphorylation State ◽  
Tyrosine Metabolism ◽  
Streptozotocin Diabetic Rats ◽  
Adrenalectomized Rats

Flux through, and maximal activities of, key enzymes of phenylalanine and tyrosine degradation were measured in liver cells prepared from adrenalectomized rats and from streptozotocin-diabetic rats. Adrenalectomy decreased the phenylalanine hydroxylase flux/activity ratio; this was restored by steroid treatment in vivo. Changes in the phosphorylation state of the hydroxylase may mediate these effects; there was no significant change in the maximal activity of the hydroxylase. Tyrosine metabolism was enhanced by adrenalectomy; this was not related to any change in maximal activity of the aminotransferase. Steroid treatment increased the maximal activity of the aminotransferase. Both acute (3 days) and chronic (10 days) diabetes were associated with increased metabolism of phenylalanine; insulin treatment in vivo did not reverse these changes. Although elevated hydroxylase protein concentration was a major factor, changes in the enzyme phosphorylation state may contribute to differences in phenylalanine degradation in the acute and chronic diabetic states. Tyrosine metabolism, increased by diabetes, was partially restored to normal by insulin treatment in vivo. These changes can, to a large extent, be interpreted in terms of changes in the maximal activity of the aminotransferase.

scholarly journals The metabolism of l-tryptophan by liver cells prepared from adrenalectomized and streptozotocin-diabetic rats

1981 ◽  
Vol 200 (3) ◽  
pp. 605-609 ◽  
Author(s):  
S A Smith ◽  
C I Pogson
Keyword(s):  
Kynurenine Pathway ◽  
Liver Cells ◽  
Diabetic Rats ◽  
Insulin Deficiency ◽  
Cell Preparation ◽  
Metabolic Fate ◽  
Carboxylase Activity ◽  
Streptozotocin Diabetic Rats ◽  
Adrenalectomized Rats

1. The metabolism of L-tryptophan by liver cells prepared from fed normal, adrenalectomized and streptozotocin-diabetic rats was studied. 2. At physiological concentrations (0.1 mM), the rate of oxidation of tryptophan by tryptophan 2,3-dioxygenase was 3-fold greater in liver cells from diabetic rats than in those from fed rats. In liver cells from diabetic rats, oxidation of tryptophan to CO2 and metabolites of the glutarate pathway was increased 7-fold. Quinolinate synthesis was decreased by 50%. These findings are consistent with an increase in picolinate carboxylase activity. 3. Rates of metabolism of 0.1 mM-tryptophan by hepatocytes from fed and adrenalectomized rats were similar. 4. In all three types of cell preparation, fluxes through tryptophan 2,3-dioxygenase with 2.5 mM-tryptophan were 7-fold greater than those obtained with 0.1 mM-tryptophan. Tryptophan 2,3-dioxygenase and kynureninase fluxes in hepatocytes from fed and adrenalectomized rats were comparable, whereas those in liver cells from diabetic rats were increased 2.5-fold and 3.3-fold respectively. Picolinate carboxylase activities of liver cells from diabetic rats were 15-fold greater than those of cells from fed rats, but rates of quinolinate synthesis were unchanged. 5. It is concluded that: (i) adrenal corticosteroids are not required for the maintenance of basal activities of the kynurenine pathway, whereas (ii) chronic insulin deficiency produces changes in both the rate of oxidation and metabolic fate of tryptophan carbon.

THE EFFECT OF INSULIN ON THE DISTRIBUTION OF GLUCOSE BETWEEN THE BLOOD PLASMA AND THE LIVER IN ALLOXAN-DIABETIC AND ADRENALECTOMIZED RATS

1963 ◽  
Vol 41 (1) ◽  
pp. 2431-2439 ◽  
Author(s):  
G. Hetenyi Jr. ◽  
F. K. Kopstick ◽  
L. J. Retelstorf
Keyword(s):  
Cell Membrane ◽  
Blood Plasma ◽  
Liver Cell ◽  
Liver Glycogen ◽  
Liver Cells ◽  
Diabetic Rats ◽  
Hepatic Cell ◽  
Very High ◽  
Adrenalectomized Rats

In diabetic rats the concentration of glucose in the liver was less than in the plasma. The relative accumulation of glucose in the liver cell after the injection of insulin was also found to be significantly less in previously untreated diabetic than in normal rats. Pretreatment with insulin restored the response to normal. Experiments with labeled glucose indicated that the rate at which glucose is carried through the hepatic cell membrane is very high compared to the rate at which glucose is being formed in the liver cells in diabetic rats. The relatively small amount of glucose accumulating after insulin in livers of diabetic rats originates from the plasma. In adrenalectomized rats which have very little liver glycogen, the relative accumulation of glucose in liver cells, following the injection of insulin, was less than that in normals. These experiments indicate that in normal rats a large part of the glucose retained in the liver after the injection of insulin originates from non-labeled endogenous hepatic sources, presumably glycogen.

THE EFFECT OF INSULIN ON THE DISTRIBUTION OF GLUCOSE BETWEEN THE BLOOD PLASMA AND THE LIVER IN ALLOXAN-DIABETIC AND ADRENALECTOMIZED RATS

1963 ◽  
Vol 41 (12) ◽  
pp. 2431-2439 ◽  
Author(s):  
G. Hetenyi Jr. ◽  
F. K. Kopstick ◽  
L. J. Retelstorf
Keyword(s):  
Cell Membrane ◽  
Blood Plasma ◽  
Liver Cell ◽  
Liver Glycogen ◽  
Liver Cells ◽  
Diabetic Rats ◽  
Hepatic Cell ◽  
Very High ◽  
Adrenalectomized Rats

In diabetic rats the concentration of glucose in the liver was less than in the plasma. The relative accumulation of glucose in the liver cell after the injection of insulin was also found to be significantly less in previously untreated diabetic than in normal rats. Pretreatment with insulin restored the response to normal. Experiments with labeled glucose indicated that the rate at which glucose is carried through the hepatic cell membrane is very high compared to the rate at which glucose is being formed in the liver cells in diabetic rats. The relatively small amount of glucose accumulating after insulin in livers of diabetic rats originates from the plasma. In adrenalectomized rats which have very little liver glycogen, the relative accumulation of glucose in liver cells, following the injection of insulin, was less than that in normals. These experiments indicate that in normal rats a large part of the glucose retained in the liver after the injection of insulin originates from non-labeled endogenous hepatic sources, presumably glycogen.

scholarly journals Regulation by insulin of glucose metabolism in mammary gland of anaesthetized lactating rats. Stimulation of phosphofructokinase-1 by fructose 2,6-bisphosphate and activation of acetyl-CoA carboxylase

1988 ◽  
Vol 254 (1) ◽  
pp. 11-14 ◽  
Author(s):  
A F Burnol ◽  
S Ebner ◽  
P Ferré ◽  
J Girard
Keyword(s):  
Mammary Gland ◽  
Glucose Metabolism ◽  
Fold Increase ◽  
Maximal Activity ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Euglycaemic Hyperinsulinaemic Clamp ◽  
Sites Of Action ◽  
Stimulation Of

The effect of insulin on glucose metabolism in mammary gland was studied by the euglycaemic/hyperinsulinaemic-clamp technique. Measurement of metabolite concentrations and enzyme activities in the mammary gland suggests two sites of action of insulin: phosphofructokinase-1 and acetyl-coA carboxylase. The increase in phosphofructokinase-1 activity could be linked to the 2-fold increase in fructose 2,6-bisphosphate concentration, since no change in maximal activity and in sensitivity of the enzyme toward fructose 6-phosphate was detected in vitro.

The role of rice bran extract on acetyl CoA carboxylase in liver of rats fed a high-fat diet

Planta Medica ◽  
2011 ◽  
Vol 77 (12) ◽  
Author(s):  
C Charkhonpunya ◽  
S Sireeratawong ◽  
S Komindr ◽  
N Lerdvuthisopon
Keyword(s):  
Rice Bran ◽  
High Fat Diet ◽  
Acetyl Coa Carboxylase ◽  
High Fat ◽  
Acetyl Coa ◽  
Rice Bran Extract

Plasminogen Activation In Vivo upon Intravenous Infusion of DDAVP

1992 ◽  
Vol 67 (01) ◽  
pp. 111-116 ◽  
Author(s):  
Marcel Levi ◽  
Jan Paul de Boer ◽  
Dorina Roem ◽  
Jan Wouter ten Cate ◽  
C Erik Hack
Keyword(s):  
Monoclonal Antibodies ◽  
Plasminogen Activator ◽  
Plasma Levels ◽  
Fold Increase ◽  
Fibrinolytic System ◽  
Plasminogen Activation ◽  
Plasminogen Activator Activity ◽  
Insight Into

SummaryInfusion of desamino-d-arginine vasopressin (DDAVP) results in an increase in plasma plasminogen activator activity. Whether this increase results in the generation of plasmin in vivo has never been established.A novel sensitive radioimmunoassay (RIA) for the measurement of the complex between plasmin and its main inhibitor α2 antiplasmin (PAP complex) was developed using monoclonal antibodies preferentially reacting with complexed and inactivated α2-antiplasmin and monoclonal antibodies against plasmin. The assay was validated in healthy volunteers and in patients with an activated fibrinolytic system.Infusion of DDAVP in a randomized placebo controlled crossover study resulted in all volunteers in a 6.6-fold increase in PAP complex, which was maximal between 15 and 30 min after the start of the infusion. Hereafter, plasma levels of PAP complex decreased with an apparent half-life of disappearance of about 120 min. Infusion of DDAVP did not induce generation of thrombin, as measured by plasma levels of prothrombin fragment F1+2 and thrombin-antithrombin III (TAT) complex.We conclude that the increase in plasminogen activator activity upon the infusion of DDAVP results in the in vivo generation of plasmin, in the absence of coagulation activation. Studying the DDAVP induced increase in PAP complex of patients with thromboembolic disease and a defective plasminogen activator response upon DDAVP may provide more insight into the role of the fibrinolytic system in the pathogenesis of thrombosis.

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