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

1. Concentrations of polyamines, amino acids, glycogen, nucleic acids and protein, and activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase, were measured in livers from control, streptozotocin-diabetic and insulin-treated diabetic rats. 2. Total DNA per liver and protein per mg of DNA were unaffected by diabetes, whereas RNA per mg of DNA and glycogen per g of liver were decreased. Insulin treatment of diabetic rats induced both hypertrophy and hyperplasia, as indicated by an increase in all four of these constituents to or above control values. 3. Spermidine content was increased in the livers of diabetic rats, despite the decrease in RNA, but it was further increased by insulin treatment. Spermine content was decreased by diabetes, but was unchanged by insulin treatment. Thus the ratio spermidine/spermine in the adult diabetic rat was more typical of that seen in younger rats, whereas insulin treatment resulted in a ratio similar to that seen in rapidly growing tissues. 4. Ornithine decarboxylase activity was variable in the diabetic rat, showing a positive correlation with endogenous ornithine concentrations. This correlation was not seen in control or insulin-treated rats. Insulin caused a significant increase in ornithine decarboxylase activity relative to control or diabetic rats. 5. S-Adenosylmethionine decarboxylase activity was increased approx. 2-fold by diabetes and was not further affected by insulin. 6. Hepatic concentrations of the glucogenic amino acids, alanine, glutamine and glycine were decreased by diabetes. Their concentrations and that of glutamate were increased by injection of insulin. Concentrations of ornithine, proline, leucine, isoleucine and valine were increased in livers of diabetic rats and were decreased by insulin. Diabetes caused a decrease in hepatic concentration of serine, threonine, lysine and histidine. Insulin had no effect on serine, lysine and histidine, but caused a further fall in the concentration of threonine.
 ...
PMID:Polyamine and amino acid content, and activity of polyamine-synthesizing decarboxylases, in liver of streptozotocin-induced diabetic and insulin-treated diabetic rats. 616 56

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

Experimental diabetes was induced in the bovine in two experiments by intravenous injection of alloxan (110 mg/kg or 60 mg/kg) in order to determine the role of insulin on nitrogen and amino acid metabolism. In experiment 1, insulin was injected to control hyperglycemia in one group of steers immediately after alloxan treatment (110 mg/kg). In experiment 2, insulin was injected beginning 6 days following alloxan treatment (60 mg/kg) to control hyperglycemia. Plasma glucose increased to 800-1400 mg/100 ml within 5-6 days following alloxan administration (experiment 1). A large surge of insulin release occurred immediately after alloxan administration, which was followed by a decrease in insulin concentrations to subnormal levels in those animals not treated with insulin. Alloxan-treated steers became acidotic by day 2 as indicated by a drop in blood pH, bicarbonate and base excess. Acid-base status improved in steers treated with alloxan plus insulin but did not return to normal. Alloxan treatment caused a marked increase in serum urea-N and creatinine concentrations and insulin treatment of the alloxanized animal decreased both serum urea-N and creatinine concentrations. Treatment with alloxan caused a two- to threefold increase in the plasma concentrations of valine, isoleucine, leucine, lysine and 3-methylhistidine and a decrease in alanine, threonine, citrulline and arginine. Insulin treatment of the alloxanized bovine maintained normal plasma concentrations of valine, isoleucine and leucine. In a third experiment, the injection of insulin (6 U/kg) into normal cattle caused a transient decline in plasma concentrations of branched-chain amino acids (BCAA); however, if glucose was continuously infused (125 mmol/hour) in addition to insulin injection, a sustained decrease in plasma BCAA concentrations was observed. These data support the concept that insulin promotes decreased plasma concentrations of BCAA either by promoting tissue anabolism by stimulating tissue uptake and protein synthesis or decreasing proteolysis and BCAA release.
 ...
PMID:Role of insulin in regulating amino acid metabolism in normal and alloxan-diabetic cattle. 634 16

When isolated rat pancreatic islets are exposed to L-leucine (20 mM), the rate of NH4 production is close to the summed rates of L-[1-14C] leucine decarboxylation and alpha-ketoisocarproate production, whereas the rates of acetoacetate production and L-[U-14C]-leucine oxidation are compatible with conversion of each mole of the amino acid to one mole of acetoacetate and three moles of CO2. ATP content, ATP/ADP ratio, and adenylate charge are maintained at normal values by L-leucine, whereas the NADH/NAD+ ratio (but not the NADPH/NADP+ ratio) is significantly increased. The release of insulin evoked by L-leucine is potentiated by 2-ketoisovalerate, unaffected by L-valine, and inhibited by menadione. L-leucine mimicks the effect of D-glucose on 86Rb+ and 45Ca2+ handling by the islets. However, relative to its rate of oxidation, the insulinotropic effect of L-leucine is less marked than that of D-glucose. This may be due, in part at least, to a decrease in the oxidation of endogenous nutrients. It is concluded that the metabolic, cationic, and secretory effects of L-leucine in isolated islets are not incompatible with the fuel hypothesis for insulin release.
Diabetes 1980 Jun
PMID:The stimulus-secretion coupling of amino acid-induced insulin release: metabolism and cationic effects of leucine. 676 28

An affinity chromatography system has been developed that retains glycosylated amino acids and peptides. Using this system, synthetic 14C-glycosylated lysine (reduced with NaB3H4) was completely separated from a mixture of reduced 14C-glycosylated lysine and unmodified 3H-lysine. Amino acid analysis of the retained peak from hydrolyzed human diabetic hemoglobin previously reduced with NaB3H4 revealed an equimolar mixture of glycosylated valine and glycosylated lysine, in agreement with previously published data obtained using other methodologies. These data demonstrate that in alkaline solution, the NaB3H4-reducible breakdown products of nonenzymatically glycosylated proteins are adsorbed to m-aminophenyl boronic acid immobilized on Bio-Gel P-6, while nonglycosylated amino acids are not. This affinity chromatography system should facilitate the rapid evaluation of nonenzymatic glycosylation in a large number of diabetic tissues. Levels of retained compounds in urine from diabetic and normal patients were determined by measuring ninhydrin-positive material. Amino acid analysis of NaB3H4-reduced hydrolysates of these peaks showed that glycosylated lysine was the major borohydride-reducible adduct present (67%--86%). Linear regression analysis showed that the quantity of excreted compounds in normals correlated with body weight (r = 0.63). The mean level (mumol leucine-equivalent/24 h/kg body weight) in diabetics was over 1.5 times that found in urine from normal subjects (P < 0.005).
Diabetes 1980 Dec
PMID:Measurement of glycosylated amino acids and peptides from urine of diabetic patients using affinity chromatography. 677 22

Alterations in plasma branched-chain amino acids (valine, isoleucine and leucine) and alanine have been described in patients with insulin-dependent diabetes mellitus who have poor metabolic control. To assess the relevance of these abnormalities as indices of metabolic control, we sequentially evaluated plasma amino acids in 14 poorly controlled diabetics (seven Type 1 (insulin-dependent) and seven Type 2 (non-insulin-dependent) patients) until good control was achieved. The sum of branched-chain amino acids in both groups of uncontrolled diabetic patients was significantly increased compared with the values for the same subjects in good metabolic control. No statistically significant differences were present between ketotic and non-ketotic uncontrolled patients. The amelioration of the diabetic state with either insulin treatment or oral hypoglycaemic agents, reduced progressively branched-chain amino acids. The sum of valine, isoleucine and leucine strictly correlated with daily urinary glucose (r = 0.73), but less well with fasting blood glucose (r = 0.43), non-esterified fatty acids (r = 0.46) and glycosylated haemoglobin (r = 0.38). Alanine did not show any statistically significant differences at various stages of diabetic control. Branched-chain amino acids, but not alanine, may be used as indices of short-term diabetic control.
 ...
PMID:Branched-chain amino acids and alanine as indices of the metabolic control in type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetic patients. 680 94

The relation between food intake and enzyme activity of the small intestine and rate of intestinal absorption were studied in rats 15 days after induction of alloxan diabetes. Diabetic rats were given an ad lib. semisynthetic diet or a restricted diet on the basis of either daily intake or body weight. The rates of absorption of 5 mMD-galactose and L-valine were determined in vitro by the everted sac method. The rates of absorption of the substances, expressed per unit weight or per length of intestine, were higher in diabetic rats than in controls, regardless of the amount of food consumed. Maltase and sucrase activities were significantly increased in diabetic rats, regardless of the amount of food consumed. The activity of intestinal alkaline phosphatase was increased in diabetic rats fed ad lib., but not in those on a restricted diet. These findings suggest that in alloxan diabetic rats the increased disaccharidase activity in the small intestine is due to insulin deficiency, and that the increased activity of alkaline phosphatase is only a secondary effect of insulin deficiency, caused by increased food intake resulting from insulin deficiency.
 ...
PMID:Effect of food intake on intestinal absorption and mucosal hydrolases in alloxan diabetic rats. 698 35

Branched-chain 2-oxo acid dehydrogenase catalyses the first irreversible step in the degradation of the branched-chain amino acids leucine, isoleucine and valine. With specifically labelled 4-methyl-2-oxo[1-14C]pentanoate as substrate, the enzyme's activity was measured in rat liver homogenates. Activity (per g wet wL of liver or per mg of protein) increased most rapidly during the perinatal period (2 days before to 1 day after birth), reaching approximately adult values by the time of weaning. The apparent Vmax, of the enzyme increased with age, but its Km appeared unchanged. The data suggest that hepatic branched-chain 2-oxo acid dehydrogenase is induced or activated during the perinatal period. The enzyme's activity at birth was unaffected by maternal diabetes, or by treating the mother with pharmacological doses of corticosterone or 3,3',5-tri-iodothyronine, during the last 5 days of pregnancy.
 ...
PMID:Developmental changes in rat liver branched-chain 2-oxo acid dehydrogenase. 711 44

In vitro perfusion and incubation studies and recent investigations in dogs suggest that branched chain amino acids (BCAA) may be a major source of alanine nitrogen. To determine the contribution of BCAA nitrogen to the formation of alanine in man, seven postabsorptive adults received prime-dose constant infusions of 15N-leucine, L-[6,6,6-2H3] leucine, and L-[2,3,3,3-2H4] alanine; isotopic enrichment was determined in arterialized venous plasma samples by gas chromatography-mass spectroscopy. At substrate and isotope steady state, alanine flux and the rate of 15N alanine appearance were 5.4 +/- 0.3 mumol/kg-min and 32 +/- 2 nmol/kg.min, respectively. Leucine nitrogen flux was significantly greater than that of leucine carbon flux (2.54 +/- 0.25 vs. 1.90 +/- 0.10 mumol/kg.min, respectively; P less than 0.001). The 30% greater flux of leucine nitrogen when compared with leucine carbon suggests significant recycling of the leucine carbon in vivo. The percent of circulating alanine nitrogen derived from leucine was 12.5 +/- 1.5%; however, the rate of leucine nitrogen transferred to alanine was 0.66 +/- 0.05 mumol/kg.min, and represents a minimum of 28% of leucine nitrogen going to alanine. On the basis of these data, together with the percent of alanine and leucine in body protein, only 40% of circulating plasma alanine could come from endogenous protein, whereas 60% is derived from de novo synthesis. In addition, at least 20% of the nitrogen required for alanine synthesis is derived solely from leucine following an overnight fast. Therefore, if the contribution of isoleucine and valine nitrogen is similar to that of leucine, the BCAA may contribute to a minimum of 60% of the nitrogen required for alanine synthesis in postabsorptive man.
Diabetes 1982 Jan
PMID:Branched chain amino acids as a major source of alanine nitrogen in man. 715 24

Branched-chain alpha-keto and amino acid (BCKA, BCAA) concentrations were measured in blood, plasma, and tissues of rats fed low protein (8% casein) or high protein (60% casein) diets; and in rats fed a stock diet and subjected to 3 days of starvation of chemically-induced diabetes. Concentrations of these amino and ketoacids were also measured in blood from patients with maple syrup urine disease. Valine, isoleucine, and leucine concentrations in blood from rats fed the stock diet were 124 +/- 7, 58 +/- 4 and 99 +/- 5 microM, respectively. Blood BCAA concentrations of rats fed the high protein diet and diabetic rats were elevated 2- to 3-fold; small increases were observed in blood from starved rats. Changes in blood BCAA concentrations paralleled those in tissues, except in starved rats in which the skeletal muscle free BCAA pool increased proportionately more than the circulating pool. Mean blood BCKA concentrations of rats fed the stock diet were low--7.9 +/- 0.5, 7.1 +/- 0.4 and 12.4 +/- 0.7 microM for alpha-ketoisovaleric, alpha-keto-beta-methylvaleric, and alpha ketoisocaproic acids, respectively. All treatments resulted in increases in blood BCKA concentrations of from 1.4 to 2 fold. In liver and heart, concentrations of BCKA, except for that of alpha-ketoisocaproic acid were near the limits of detection (less than 1 nmole/g). There was significant accumulation of all three BCKA in skeletal muscle which was estimated to contain about 80% of the measured body free BCKA pool. Blood BCKA are well regulated. Only in patients with maple syrup urine disease are plasma concentrations of BCKA useful indicators of altered tissue BCAA metabolism. Skeletal muscle, where oxidation of the BCKA is limited by low BCKA dehydrogenase activity, would seem to be the major source of circulating BCKA.
 ...
PMID:Blood and tissue branched-chain amino and alpha-keto acid concentrations: effect of diet, starvation, and disease. 721 22


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>