Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Previous work has shown that the diabetogenic action of streptozotocin is reduced in rats adapted to a high-protein, carbohydrate-free diet and that plasma valine, leucine and isoleucine concentrations are markedly elevated in rats adapted to the high-protein diet. 2. To test the possibility that these branched-chain amino acids play a role in the beneficial effects of the high-protein diet, rats fed the control balanced diet were injected intraperitoneally with mixtures of valine, leucine and isoleucine (0.25 or 0.50 g/kg body weight of each amino acid), or with each of these amino acids separately (0.50 g/kg), 15 min before streptozotocin administration (40 mg/kg, intravenously). Arginine (0.50 g/kg) was administered in one experiment. Control animals received equal volumes of saline. 3. Rats previously injected with the amino acid mixtures showed a partial but significant reduction of diabetes severity as indicated by lower plasma glucose levels, higher rates of body weight gain and greater amounts of epididymal and retroperitoneal fat. No protection was observed after the administration of either valine, isoleucine, leucine or arginine. 4. These data suggest that the elevated levels of plasma branched-chain amino acids may account at least in part for the initial protective effect of high-protein diets against streptozotocin beta-cytotoxicity when the cells are first exposed to the drug.
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PMID:Administration of branched-chain amino acids reduces the diabetogenic effect of streptozotocin in rats. 296 88

Diabetes mellitus is a defect not only in glucose metabolism, but also in the metabolism of lipids and amino acids. Gas chromatographic and gas chromatographic--mass spectrometric profile analyses have contributed much to the understanding of the metabolic changes connected with this defect. Ketones are isolated by a gas-phase extraction and adsorption technique and profiled after thermal desorption. Organic acids are isolated by solvent extraction or anion exchange, derivatized and separated either as total acid profiles or subprofiles after pre-fractionation of the acid derivatives. The main results are as follows. (a) Increased total 4-heptanone is inherently connected with diabetes mellitus. Its urinary levels are elevated in therapeutically well controlled patients. (b) A general ketogenesis pathway leads to higher molecular weight ketone bodies in addition to the conventional ketone bodies. (c) During diabetic ketoacidosis, in addition to the fatty acids the following acids are elevated in serum and in urine: dicarboxylic acids resulting from omega- and beta-oxidation of monocarboxylic acids; oxomonocarboxylic acids as metabolites of the amino acids valine, leucine and isoleucine and as products of ketogenesis; and hydroxymonocarboxylic acids, also originating from amino acids and from ketogenesis.
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PMID:Gas chromatographic profiling of ketone bodies and organic acids in diabetes. 309 87

Previous studies showed that the diabetogenic action of streptozotocin is reduced in rats adapted to a high-protein, carbohydrate-free diet, that have markedly elevated plasma concentrations of valine, leucine and isoleucine. In order to test the role of these branched chain amino acids (BCAA) in the beneficial effects of the high-protein diets, rats adapted (15 days) either to a balanced synthetic diet, or to the same diet supplemented with BCAA were injected with streptozotocin (STZ) (40 mg/kg body weight) and maintained on the same diets after drug injection. Rats previously fed the BCAA enriched diet showed a partial but significant reduction in the severity of diabetes, as indicated by higher rates of body weight gain, lower food and water intake, lower excretion of glucose and higher serum insulin levels. Rats previously fed the control diet for 14 days, but transferred to the BCAA diet 3 days after STZ injection, also showed reduced severity of diabetes, as indicated by rates of body weight gain, water and food ingestion, glucose and insulin levels. The data suggest that the increased supply of BCAA is responsible, at least in part, for the previously reported beneficial effects of high-protein diets in rats with STZ-induced diabetes.
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PMID:Dietetic supplementation with branched chain amino acids attenuates the severity of streptozotocin-induced diabetes in rats. 322 89

We describe a family from Japan displaying the mutant insulin syndrome with hyperinsulinaemia and an increased insulin: C-peptide molar ratio. Serum insulin isolated from several family members showed reduced in vitro biological activity, and analysis by high performance liquid chromatography revealed a peak co-eluting with human insulin and a second species of increased hydrophobicity co-migrating with the previously reported Insulin Wakayama. The insulin genes from the propositus were cloned and sequenced, revealing one normal allele; the second allele, encoding a leucine for valine amino acid substitution at position 3 of the insulin A chain, was similar to that previously described for Insulin Wakayama. Synthesized [LeuA3] insulin showed 0.14% of receptor binding activity on rat adipocytes and a 10-fold prolonged half-life in a somatostatin-infused dog compared with human insulin. The finding of the same mutant gene in two unrelated Japanese families suggests that Insulin Wakayama may be discovered in additional Japanese families with hyperinsulinaemia and/or diabetes.
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PMID:Insulin Wakayama: familial mutant insulin syndrome in Japan. 355 28

Plasma amino acid concentrations were measured in six insulin-dependent diabetic women and seven non-diabetic women in early pregnancy while fasting and one hour after a standard meal. Fasting plasma levels of total amino acids and individual amino acids were similar in the two groups, excepting isoleucine, which was raised in the diabetics. One hour post-prandially total amino acid concentrations were similar in the two groups; however, mean concentrations of total branched chain amino acids and mean concentration of the individual amino acids, serine, valine, isoleucine, leucine and tyrosine were elevated in the diabetics. Amino acids are important in early islet development and in insulin secretion from fetal pancreas in vitro. The elevated post-prandial amino acid levels found in pregnant diabetics in early pregnancy may contribute to fetal islet hypertrophy and hyperinsulinaemia.
Diabetes Res Clin Pract 1986 Jun
PMID:Amino acid profiles in early diabetic and non-diabetic pregnancy. 374 58

An 8.75-yr-old Caucasian boy was discovered to have a markedly elevated (14.8%) hemoglobin A1c (HbA1c) as estimated by ion-exchange chromatography (Bio Rex 70). Glycohemoglobin (GHb) measured by a colorimetric method with thiobarbituric acid (TBA) was normal (equivalent to a 6.4% HbA1c). Nondiabetic quantities of GHb were found with affinity chromatography, and the glucose tolerance test was normal. Intensive efforts to identify an abnormal variant hemoglobin by several electrophoretic methods were unsuccessful. A family survey identified a similar abnormality in 11 other individuals, revealing an autosomal-dominant pattern. None of the affected individuals had any other hematologic abnormality. Structural analysis in one family member revealed a new hemoglobin variant (approximately 45% of the total hemoglobin) with the substitution of methionine for valine at the beta-NH2-terminal. In addition, the initiator methionine residue was preserved. Approximately 20% of the variant hemoglobin was modified by acetylation of the NH2-terminal methionine. The modified variant coeluted with HbA1c. We suggest that patients who do not have an explanation for their elevated HbA1c should have GHb measured by the TBA method or affinity chromatography because hemoglobin electrophoresis does not identify this confounding artifact.
Diabetes 1986 Oct
PMID:Hemoglobin South Florida. New variant with normal electrophoretic pattern mistaken for glycosylated hemoglobin. 375 92

Insulin-dependent diabetes mellitus (IDDM) induces plasma amino acid (AA) abnormalities, including low alanine and high branched-chain (BCAA). While insulin treatment restores plasma AA pattern, proline, methionine, valine, isoleucine, and total BCAA remain elevated in skeletal muscle intracellular water. This suggests that the restoration of plasma AA concentrations is not a satisfactory index of recovered AA metabolism in IDDM.
Diabetes 1985 Aug
PMID:Plasma and skeletal muscle free amino acids in type I, insulin-treated diabetic subjects. 389 23

In vitro catabolism of branched-chain amino acids, leucine and valine, was investigated using diaphragm muscles from normal, streptozotocin-diabetic and overnight fasted rats. Oxidation and transamination of [1-14C] branched-chain amino acids were both stimulated to a similar extent by diabetes or fasting, when diaphragms were incubated with glucose. Transamination of leucine and valine was increased when diaphragms were incubated with pyruvate; stimulation of transamination was greatest in diaphragms from diabetic rats. Leucine and valine oxidation by control diaphragms was inhibited by pyruvate while it was unchanged or slightly stimulated in diaphragms from fasted or diabetic rats. Thus diaphragms from diabetic rats oxidized two to threefold more branched-chain amino acids than controls when they were incubated with pyruvate. The specific radioactivity of extracellular alpha-ketoisocaproate (KIC; the product of leucine transamination) produced by diaphragms incubated with [14C]leucine was similar for all groups (fed, fasted, or diabetic) in the presence or absence of pyruvate. Oxidation of [1-14C]KIC by diaphragms from fasted or diabetic rats, incubated with glucose, was the same or less than KIC oxidation by control diaphragms. Incubation with pyruvate inhibited KIC oxidation by control diaphragms to a significantly greater degree than that by diaphragms from diabetic or fasted rats. These data suggest the following Flux through branched-chain amino acid transaminase is limited by the availability of amino group acceptors in diaphragms from normal and overnight fasted rats, and to a greater extent in diaphragms from diabetic rats. Flux through the transaminase may be a major determinant of accelerated branched-chain amino acid oxidation by diaphragms in fasting and diabetes. In diaphragms of fasted and diabetic rats, flux through the branched-chain alpha-ketoacid dehydrogenase complex is resistant to inhibition by pyruvate, which is normally observed in controls.
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PMID:Catabolism of branched-chain amino acids by diaphragm muscles of fasted and diabetic rats. 402 2

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

1. The effect of three types of diabetes (alloxan, partial pancreatectomy and anti-insulin serum) on the concentrations of individual amino acids in the plasma and heart muscle of rats was studied. 2. Insulin deficiency produced complex alterations in the concentrations of amino acids in plasma and heart muscle; the concentrations of some (alanine, valine, leucine and isoleucine) increased, others decreased and a small number were unchanged. The complexity of the results may in part be attributed to the diverse hormonal and metabolic changes that accompany diabetes.
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PMID:Effect of diabetes on the concentration of amino acids in plasma and heart muscle of rats. 596 35


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