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)

The protein anabolic effect of branched chain amino acids was studied in isolated quarter diaphragms of rats. Protein synthesis was estimated by measuring tyrosine incorporation into muscle proteins in vitro. Tyrosine release during incubation with cycloheximide served as an index of protein degradation. In muscles from normal rats the addition of 0.5 mM leucine stimulated protein synthesis 36--38% (P less than 0.01), while equimolar isoleucine or valine, singly or in combination were ineffective. The three branched chain amino acids together stimulated no more than leucine alone. The product of leucine transamination, alpha-keto-isocaproate, did not stmino norborane-2-carboxylic acid (a leucine analogue) were ineffective. Leucine and isoleucine stimulated protein synthesis in muscles from diabetic rats.Leucine, isoleucine, valine and the norbornane amino acid but not alpha-ketoisocaproate or beta-hydroxybutyrate decreased the concentration of free tyrosine in tissues during incubation with cycloheximide; tyrosine release into the medium did not decrease significantly. Leucine caused a small decrease in total tyrosine release, (measured as the sum of free tyrosine in tissues and media), suggesting inhibition of protein degradation. The data suggest that leucine may be rate limiting for protein synthesis in muscles. The branched chain amino acids may exert a restraining effect on muscle protein catabolism during prolonged fasting and diabetes.
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PMID:Studies concerning the specificity of the effect of leucine on the turnover of proteins in muscles of control and diabetic rats. 13 65

In normal man, the fasting state is characterized by release of alanine and glutamine from muscle and in situ muscle catabolism of branched chain amino acids (lecucine, isoleucine, and valine). The alanine released by muscle is utilized by the liver for gluconeogenesis. Muscle nitrogen repletion occurs during protein feeding primarily by means of selective hepatic escape and muscle uptake of branched chain amino acids in ingested protein. In the diabetic, amino acid catabolism is exaggerated in the fasting state as reflected by increased uptake of alanine by the liver for gluconeogenesis and accelerated branched chain amino acid catabolism in muscle. After protein feeding, uptake of branched chain amino acids by muscle is reduced and these amino acids accumulate in increased amounts in arterial blood. Protein feeding also exaggerates the hyperglycemia of diabetes by causing an increase in hepatic glucose production. Diabetes is thus characterized by accelerated protein catabolism during fasting as well as diminished nitrogen repletion and hyperglycemia after protein feeding. The hyperketonemia of diabetes may however, have a restraining influence on protein catabolism thereby reducing alanine availability for gluconeogenesis.
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PMID:Amino acid and protein metabolism in diabetes mellitus. 40 71

The effect of L-carnitine (0.5-2.0 mM) on the rates of alpha-decarboxylation of 1-14C-labeled branched-chain amino acids by gastrocnemius muscle and liver homogenates of fed rats was investigated. Carnitine increased the rate of alpha-decarboxylation of leucine (125%) and valine (28%) by muscle, but it was without effect on the oxidation of these amino acids by liver. Carnitine increased the rate of alpha-decarboxylation of alpha-ketoisocaproate by both tissues. This effect was more pronounced in muscle (130% increase) than in liver (41% increase). The activity of carnitine acyltransferase, with isovaleryl-CoA as a substrate, was 18 times higher in muscle mitochondria than in liver mitochondria. Both starvation and diabetes increased the rate of alpha-decarboxylation of leucine by muscle without having a remarkable effect on the concentration of carnitine or the activity of carnitine acyltransferase. We conclude that: a) carnitine stimulates decarboxylation of branched-chain amino acids by increasing the conversion of their ketoanalogues into carnitine esters, b) a greater carnitine acyltransferase activity in muscle than in liver may be responsible for the greater carnitine effect in muscle, c) carnitine does not appear responsible for the enhancement of leucine oxidation by muscle of starved and diabetic rats.
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PMID:Effect of carnitine on branched-chain amino acid oxidation by liver and skeletal muscle. 64 1

Diabetes is known to produce increased levels of the branched chain amino acids in plasma, heart and muscle as well as increased oxidation of [14C]-leucine by nerves and muscles from rats. Plasma and retinas from streptozotocin diabetic rats had significant elevations in branched chain amino acid levels compared to control. Retinas from diabetic rats have been found to oxidize significantly more of the branched chain amino acids, leucine, isoleucine and valine than did control retinas when incubated in media containing 16.5 mmol/l glucose. Neither the extracellular space nor the tissue pool of leucine was significantly different in the two groups. The addition of 19 amino acids, at normal plasma concentrations, to the incubation media resulted in 80 percent suppression of leucine oxidation without significant change in incorporation of [14C] into protein. These results suggest that the major role for the branched chain amino acids in the rat retina is in protein synthesis which is not affected by short-term diabetes.
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PMID:Branched chain amino acid metabolism in the retina of diabetic rats. 65 33

The amino acid pattern following total hip replacement is characterized by increases in muscle of the branched chain amino acids (leucine, isoleucine and valine), the aromatics (phenylalanine and tyrosine) as well as methionine. The nonessential amino acids in muscle tend to decline, glutamine having the most marked change. Plasma levels of the essential amino acids increase while the nonessentials tend to decrease. This pattern differs from that observed in other catabolic states (uremia, starvation, untreated diabetes) and is significantly different from the effects of inactivity and starvation combined. This suggests that injury can be characterized by a unique pattern of muscle and plasma amino acids.
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PMID:Muscle and plasma amino acids after injury: the role of inactivity. 73 57

To evaluate the effect of insulin-saline-bicarbonate therapy on amino acid metabolism in diabetic ketoacidosis, arterial and venous blood samples as well as cerebrospinal fluid (CSF) were obtained from six patients before and after initiation of corrective therapy. Levels of CSF glutamine were decreased while alanine alpha-amino-n-butyrate, valine, isoleucine and leucine were increased significantly compared to a control group composed of six normal, postabsorptive adults free of any neurologic disease. Following therapy, CSF levels of alanine, alpha-amino-n-butyrate, valine, isoleucine, and leucine declined while glutamine levels did not change. Admission arterial plasma levels of the glycogenic amino acids were lower than normal while the branched-chain amino acids were elevated. Plasma alanine and glutamine arterio-venous (A-V) differences across forearm tissue were larger. After four hours of corrective therapy, arterial plasma levels of most of the amino acids had declined sharply and A-V differences for glutamine and alanine were markedly reduced (p smaller than.025 and p smaller than.01, paired t, respectively). Coincident with the decrease in A-V amino acid differences, plasma glucagon and free fatty acid levels declined significantly. These data suggest that the effect exerted by insulin-saline-bicarbonate therapy on amino acid metabolism is manifested by diminished A-V plasma alanine and glutamine differences across forearm tissue. Thus, the role played by the splanchnic bed both before and following corrective measures may be secondary to substrate availability.
Diabetes 1975 May
PMID:Plasma and cerebrosponal fluid amino acid levels in diabetic ketoacidosis before and after corrective therapy. 80 76

Hemoglobin AIc is a minor component of normal adult erythrocytes whose concentration is elevated approximately 2-fold in patients with diabetes mellitus. Previous work suggested that the unique structural feature of hemoglobin AIc is the presence of a low molecular weight sugar moiety at the NH2-terminal valine of the beta chain. In this study the structure of the carbohydrate moiety and the nature of its linkage of the beta chain were investigated. Enzymatic digestion of borohydride-reduced betaAIc chains followed by ion exchange chromatography led to the isolation of two distinct NH2-terminal glycovalylhistidines. Comparison of these glycodipeptides with synthetic glycovalylhistidines by thin layer chromatography, gas-liquid chromatography, and proton magnetic resonance spectroscopy gave direct evidence that the naturally derived materials correspond to glucitol and mannitol valylhistidines. Model reactions showed that glucose and mannose react with valine under mild conditions to form an adduct which upon sodium borohydride reduction yields in both cases glucitol and mannitol valines. This suggests a common intermediate, 1-deoxy-1-(N-valyl)fructose, for both reactions. From these studies we conclude that hemoglobin AIc has, as the NH2 terminus of the beta chain, 1-deoxy-1-(N-valyl)fructose. The possible biosynthetic pathways of hemoglobin AIc are discussed.
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PMID:Structure of carbohydrate of hemoglobin AIc. 85 40

The inter-organ flux of substrates after a protein-rich meal was studied in seven healthy subjects and in eight patients, with diabetes mellitus. Arterial concentrations as well as leg and splanchnic exchange of amino acids, carbohydrate substrates, free fatty acids (FFA), and ketone bodies were examined in the basal state and for 3 h after the ingestion of lean beef (3 g/kg body wt). Insulin was withheld for 24 h before the study in the diabetic patients. In the normal subjects, after protein ingestion, there was a large amino acid release from the splanchnic bed predominantly involving the branched chain amino acids. Valine, isoleucine, and leucine accounted together for more than half of total splanchnic amino acid output. Large increments were seen in the arterial concentrations of the branched chain amino acids (100-200%) and to a smaller extent for other amino acids. Leg exchange of most amino acids reverted from a basal net outut to a net uptake after protein feeding which was most marked for the branched chain amino acids. The latter accounted for more than half of total peripheral amino acid uptake...
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PMID:Effect of protein ingestion on splanchnic and leg metabolism in normal man and in patients with diabetes mellitus. 94 63

Glomerular basement membrane (GBM) and tubular basement membrane (TBM) were prepared from human kidneys of diabetics and non-diabetics, and their chemical composition was compared. GBM from diabetics contained a larger amount of hydroxyproline than that from non-diabetics, and smaller amounts of half-cystine, glucose, mannose and sialic acid. On the other hand, TBM from diabetics contained larger amounts of hydroxylysine, methionine, galactose, hexosamine and phospholipid phosphorus than non-diabetics, and smaller amounts of half-cystine, valine, leucine, lysine and histidine. No significant difference was observed in the contents of other components examined in this study between the corresponding membrane obtained from diabetics and non-diabetics. The observed changes may be due to alteration of the tissues in diabetes mellitus.
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PMID:Comparison of the chemical composition of glomerular and tubular basement membranes obtained from human kidneys of diabetics and non-diabetics. 113 45

Incorporation of radiolabeled precursors into muscle proteins was studied in isolated rat hemidiaphragms. A mixture of three branched-chain amino acids (0.3 mM each) added to media containing glucose stimulated the incorporation of [14C]lysine into proteins. When tested separately, valine was ineffective, isoleucine was inhibitory, but 0.5 mM leucine increased the specific activity of muscle proteins during incubation with [14C]lysine or [14C]acetate in hemidiaphragms from fed or fasted rats incubated with or without insulin. Preincubation with 0.5 mM leucine increased the specific activity of muscle proteins during a subsequent 30- or 60-min incubation with [14C]lysine or [14C]pyruvate without leucine. Preincubation with other amino acids (glutamate, histidine, methionine, phenylalanine, or tryptophan) did not exert this effect. When hemidiaphragms were incubated with a mixture of amino acids at concentrations found in rat serum and a [14C]lysine tracer, the specific activity of muscle proteins increased when leucine in the medium was raised from 0.1 to 0.5 mM. Experiments with actinomycin D and cycloheximide suggested that neither RNA synthesis nor protein synthesis are required for the initiation of the leucine effect. Leucine was not effective when added after 1 h preincubation without leucine. The concentration of lysine in the tissue water of diaphragms decreased during incubation with 0.5 mM leucine in the presence or absence of cycloheximide, suggesting that leucine inhibited protein degradation. During incubation with [3h]tyrosine (0.35 mM) the addition of 0.5 mM leucine increased the specific activity of muscle proteins, while the specific activity of intracellular tyrosine remained constant and its concentration decreased, suggesting that leucine also promoted protein synthesis. The concentration of leucine in muscle cells or a compartment thereof may play a role in regulating the turnover of muscle proteins and influence the transition to negative nitrogen balance during fasting, uncontrolled diabetes, and the posttraumatic state. Leucine may play a pivotal role in the protein-sparing effect of amino aicds.
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PMID:Leucine. A possible regulator of protein turnover in muscle. 123 98


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