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.

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 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.

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.

Effects of acute insulin deficiency on catecholamine and indoleamine content and catecholamine turnover in microdissected hypothalamic nuclei in streptozotocin-diabetic rats

1989 ◽  
Vol 120 (3) ◽  
pp. 343-350 ◽  
Author(s):  
E. H. Oliver ◽  
J. L. Sartin ◽  
G. Dieberg ◽  
C. H. Rahe ◽  
D. N. Marple ◽  
...  
Keyword(s):  
Rapid Onset ◽  
Diabetic Rats ◽  
Female Rats ◽  
Insulin Deficiency ◽  
Turnover Rates ◽  
Catecholamine Turnover ◽  
Hypothalamic Nuclei ◽  
Streptozotocin Induced Diabetes ◽  
Streptozotocin Diabetic Rats ◽  
Induced Changes

Abstract. The effects of streptozotocin-induced diabetes on catecholamine and indoleamine concentrations and catecholamine turnover rates in individual microdissected hypothalamic nuclei known, or believed, to be involved in the control of neuroendocrine function, were examined in control, insulin-treated diabetic and acutely insulin-withdrawn diabetic female rats. Streptozotocin-induced diabetes and acute insulin deficiency were demonstrated to result in increased concentrations of epinephrine in the suprachiasmatic nucleus, decreased turnover of epinephrine in the arcuate nucleus and decreased turnover of dopamine in the ventromedial nucleus was found to be increased in the insulin-treated diabetic animals. These data indicate that experimental diabetes and acute insulin deficiency result in the rapid onset of detectable alterations in epinephrine and dopamine activity in specific hypothalamic nuclei. These diabetes-induced changes may cause, or contribute to, the development of secondary neuroendocrine abnormalities known to occur in the diabetic condition.

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