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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although different forms of diabetes are known to exist, there are a number of factors which occur in these states all of which would contribute to an increase in the synthesis of the kynurenine metabolites of tryptophan, xanthurenic acid in particular. Conditions giving rise to increased kynurenine metabolism include pregnancy, oral contraceptives, emotional and metabolic stress. We propose a mechanism by which kynurenines act to reduce the concentration of active insulin in plasma and thus give rise to a diabetic state.
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PMID:The role of kynurenines in diabetes mellitus. 391 51

The effect of diabetes (streptozotocin, 65 mg/kg ip), dietary protein intake (15-60%), and plasma amino acid concentrations on brain large neutral amino acid levels in rats was examined. After 20 days, the plasma concentrations of methionine and the branched chain amino acids (BCAA), valine, isoleucine, and leucine were increased in diabetic rats. In brain tissue, methionine and valine levels were increased but threonine, tyrosine, and tryptophan concentrations were depressed. Increased protein consumption promoted a diabetic-like plasma amino acid pattern in normal rats while enhancing that of diabetic animals. However, with the exception of threonine, glycine, valine, and tyrosine, there was little effect on brain amino acid levels. A good association was found between the calculated brain influx rate and the actual brain concentration of threonine, methionine, tyrosine, and tryptophan in diabetic animals. There was no correlation, however, between brain influx rate and brain BCAA levels. Thus, the brain amino acid pattern in diabetes represents the combined effects of insulin insufficiency and composition of the diet ingested on plasma amino acid levels as well as metabolic adaptation within the brain itself.
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PMID:The effect of insulin deficiency, dietary protein intake, and plasma amino acid concentrations on brain amino acid levels in rats. 404 90

Previous studies have demonstrated that the secretion of human prolactin is regulated primarily by factors that influence catecholamines of the hypothalamus. In an effort to identify other factors that may regulate prolactin secretion, the amino acid L-tryptophan, a precursor in the synthesis of serotonin, was infused into normal human volunteers. Intravenous infusion of L-tryptophan, 5-10 g over a 20 min period, but not equivalent amounts of 17 other amino acids, induced marked increases in serum prolactin concentrations in eight normal human volunteers. Increases of 20-200 ng/ml above the control level were observed with peak values at 20-45 min after initiation of the infusion. In addition, infusion of L-tryptophan was associated with decreases in serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and thyrotropin in those subjects in whom the base-line serum hormone concentration was above the lower limits of assay detectability. No consistent change was observed in serum concentrations of growth hormone, cortisol, or glucose. Four subjects with juvenile diabetes demonstrated increases in serum prolactin values comparable with those observed in healthy individuals in response to infusions of L-tryptophan. Serum prolactin values in patients with surgically induced hypopituitarism were undetectable or deficient after infusion of 10 g of L-tryptophan. In this respect, infusion of L-tryptophan was equally effective in these subjects as the standard chlorpromazine stimulation test in identifying patients with hypopituitarism, indicating that the infusion of L-tryptophan may serve as a sensitive and reliable clinical test of prolactin secretory reserve. Further studies relating to the possible mechanism of action of L-tryptophan indicated that infusion of 5-hydroxytryptophan represents a much more potent stimulus for the secretion of prolactin and that premedication with the serotonin antagonist, methysergide maleate, serves to blunt the effect of L-tryptophan on prolactin secretion. These results support the concept that the effect of L-tryptophan on the secretion of human prolactin is mediated through its conversion to serotonin and are consistent with reported experimental observations that serotonin may participate in the reciprocal regulation of prolactin and gonadotropins.
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PMID:Stimulation of human prolactin secretion by intravenous infusion of L-tryptophan. 454 74

Free amino acid concentrations have been determined in plasma and urine of nonketotic, severely diabetic dogs and age-matched normal controls. Plasma from fasted (as well as fed) diabetics contained supranormal concentrations of several amino acids, including the branched-chain amino acids. In contrast to other species, however, the concentration of only one plasma amino acid (tryptophan) was subnormal in fasted diabetic dogs. Urine collected at the same time showed that the excretion of most amino acids was not abnormal in diabetes. Urinary concentrations of some amino acids were not abnormal despite supranormal levels in plasma. Nevertheless, eight of the 21 amino acids studied reached concentrations significantly greater than normal in the urine of diabetic dogs. Six of the eight amino acids (arginine, histidine, phenylalanine, tyrosine, tryptophan, glutamic acid) showed elevated concentrations in urine even though their plasma concentrations were not elevated. The observed disturbance in the urine/plasma ratio of certain amino acids suggests a possible defect in the renal handling of amino acids in diabetes.
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PMID:Abnormal amino acid concentrations in plasma and urine of experimentally diabetic dogs. 613 39

Male, Syrian hamsters were rendered diabetic by either alloxan (60 mg/kg, i.v.) or streptozotocin (65 mg/kg, i.p.). Diabetic animals had reduced pineal melatonin contents during the night. Basal daytime values were not significantly altered. Diabetes may decrease melatonin synthesis by reducing the availability of glucose for metabolism or by decreasing the transport of tryptophan into pinealocytes for the synthesis of melatonin.
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PMID:Experimentally-induced diabetes reduces nocturnal pineal melatonin content in the Syrian hamster. 613 84

Patients studied during recovery from an episode of ketoacidotic diabetes had raised blood glucose, plasma free fatty acid and plasma free tryptophan concentrations. Plasma total tryptophan was decreased. Well controlled diabetics showed normal values. The ketoacidotic patients had increased lumbar CSF tryptophan and 5-hydroxyindoleacetic acid concentrations. Plasma tyrosine and CSF tyrosine and homovanillic acid concentrations were normal in both diabetic groups. The results are discussed in relation to somewhat similar findings in uraemic and hepatic encephalopathy and to changes in rats with streptozotocin diabetes.
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PMID:Brain transmitter precursors and metabolites in diabetic ketoacidosis. 618 Dec 9

Alterations in brain tryptophan levels and the rate of hepatic tryptophan metabolism by tryptophan oxygenase (TPO) were studied in male Sprague-Dawley rats rendered diabetic by intravenous administration of streptozotocin (STZ), 65 mg/kg. Determinations were made at the early onset of diabetes (1-4 days of glucosuria) and 8-12 days following STZ injection. Rats were considered diabetic if their serum glucose exceeded 250 mg percent. Tryptophan brain levels decreased by 17% after four days of diabetes, decreased by 22% on day 5, and by 27% 8-12 days after STZ. Brain 5-hydroxyindoleacetic acid levels were significantly decreased by 27% on day 5, but returned to control levels by 8-12 days. Serotonin concentration in the brain remained at control values. The initial appearance of a significant increase in total TPO activity coincided with the onset of a change in brain tryptophan. Total TPO activity increased by 60% after 4 days of diabetes. The increase was caused by an increase in apoenzyme activity since holoenzyme activity remained unaltered. Holoenzyme activity was increased by 37% after 8-12 days, and accounted for the change in total TPO activity. Insulin treatment reversed the STZ-induced alterations. The results are compatible with the hypothesis that diabetes increases hepatic TPO activity that in turn results in decreased plasma tryptophan levels and decreased availability of tryptophan for brain uptake. However, compensatory changes appear to maintain a stable serotonin concentration in the brain. The early and later changes in TPO activity during diabetes are apparently caused by different regulatory events.
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PMID:Effect of streptozotocin-induced diabetes on tryptophan oxygenase activity and brain tryptophan levels in rats. 619 20

Male rats treated 3 wk earlier with streptozotocin showed abnormally high blood levels of leucine, isoleucine, and valine throughout the 24-h period. Serum phenylalanine levels were slightly increased, while those of tryptophan and tyrosine were occasionally reduced. In brain, the level of each branched-chain amino acid was significantly increased above normal at all times. The brain concentration of each aromatic amino acid was always below normal. These changes were restored almost to normal by exogenous insulin therapy. Since the ingestion of protein is normally a major factor influencing blood amino acid levels, the effect of ingesting single, protein-containing meals on the blood and brain levels of these amino acids was also studied. After an overnight fast, the ingestion of a protein-containing meal by diabetic rats increased substantially both blood and brain levels of each branched-chain amino acid. No such increases occurred in normal rats. Ingestion of this meal produced only small changes in the brain and blood levels of the aromatic amino acids in both diabetic and normal rats. The changes in the brain level of each large neutral amino acid in some cases paralleled those in its blood level. More often, they paralleled the changes in the blood ratio of each amino acid to the sum of the other aromatic and branched-chain amino acids. This ratio is often a good predictor of the competitive transport of these amino acids into brain (Fernstrom and Faller, 1978). The observed changes in the brain levels of these amino acids in diabetes may influence the rates at which they are consumed in metabolic pathways within this organ.
Diabetes 1983 Mar
PMID:Effect of experimental diabetes on the levels of aromatic and branched-chain amino acids in rat blood and brain. 633 1

This volume details the history of vitamin B6, its chemistry and biochemistry, methods for the assessment of vitamin B6 status, and the clinical chemistry of the vitamin. Since its discovery and synthesis over 40 years ago, vitamin B6 has been implicated in a number of disease states. All approaches to the assessment of vitamin B6 status--direct measurement of blood levels, measurement of the excretion rate of the vitamin, measurement of the metabolites or abnormal metabolic products resulting from a deficient state, or measurement of some other process dependent on the concentration of the vitamin in the body--have significant technical or physiological problems. Dietary allowances vary for different age groups and situations. In the US, the National Academy of Sciences has recommended a daily dietary allowance of 2.2 mg for young adult males and 2.0 mg for young adult females. Additional allowances have been suggested for women during pregnancy and lactation, but not for users of oral contraceptives (OCs). Vitamin B6 deficiency can be either exogenous (when intake falls below the recommended dietary allowance) or conditioned (in cases where the physiologic requirement for the vitamin is higher than the dietary allowance). Conditioned deficiency arises in the following situations: defective intestinal absorption, defective cellular and intercellular transport, and impaired oxidtion or phosphorylation mechanisms in vitamin B6 metabolism. Studies aimed at assessing the abnormal tryptophan metabolism observed in some OC users have produced conflicting results. It appears that severe depression and impairment of glucose tolerance are the only important abnormalities encountered in OC users related to vitamin B6 deficiency. Abnormalities of tryptophan metabolism have been noted in patients with rheumatoid arthritis, some malignant diseases, liver disease, diabetes mellitus, atherosclerosis, and hyperkinetic syndromes.
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PMID:Clinical chemistry of vitamin B6. 639 13

Xanthurenic acid (XA), kynurenic acid (KA) and creatinine in fasting urine were determined by reversed phase high pressure liquid chromatography in order to investigate the distortion of tryptophan metabolites in diabetes mellitus. The results of ten patients with non-insulin dependent diabetes mellitus and ten normal healthy subjects were compared. No tryptophan load test was performed in this study, because tryptophan loading produces further latent shortage of active vitamin B6 which results in exacerbation of the disease. The ratios of XA to KA and to creatinine were 0.35 +/- 0.099 (mean +/- S.D.) and 0.99 +/- 0.321 in the diabetic patients. The corresponding figures in the normal subjects were 0.17 +/- 0.064 and 0.55 +/- 0.22. Both ratios were significantly higher in the diabetic patients than in normal subjects (p less than 0.001 and p less than 0.01, respectively). This means that XA was excessively excreted in diabetic patients resulting in distortion of tryptophan metabolism. Our findings indicated that the ratios are useful to monitor excess XA excretion and also for detection of diabetes.
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PMID:Studies on the urinary excretion of xanthurenic acid in diabetics. 652 81


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