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)

I have discussed five aspects of lens metabolism and their possible relationship to cataract in man, and this has left me with five fundamental questions to be answered. 1. Are the fluorescent tryptophan derivatives, found only in the lens of man and higher primates, involved in the development of brown nuclear cataract? 2. Is naphthalene cataract in rabbits a model for any type of cataract in man--i.e., are quinones ever formed in the human eye? 3. Is diabetes the only cataract in which osmotic swelling is important? 4. Does self-digestion of protein in the human lens contribute to cataract development? 5. Are the consequences of the abnormal maturation of lens fibers, which occurs in tryptophan deficiency cataract in rats, ever seen in man?
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PMID:Experimental studies on cataract. 96 16

Effects of histidine or methionine imbalance and dietary levels (3-50%) of casein on food intake and preference of young, adult, and diabetic (2.5 month old) rats were examined. Depressions in food intake and growth caused by ingestion of the imbalanced diet were greatest in young rats and least or absent in diabetic rats. Alloxan diabetes induced hyperphagia and elevated concentrations of plasma branched-chain amino acids and decreased concentrations of tryptophan and tyrosine. The diabetic rats fed the imbalanced diet for 9 days had a higher concentration of the limiting amino acid in the plasma than the adult normal rats fed the same diet. The diabetic rats preferred the imbalanced diet over a protein-free diet when they were fed these diets concurrently. Ingestion of the imbalanced diet by normal rats caused greater changes in plasma and brain amino acid patterns than did the protein-free diet. Unlike the diabetic rats, the normal rats, especially the young rats, strongly preferred the protein-free diet over the imbalanced diet. The normal rats also preferred a 10% casein diet supplemented with L-methionine over a low or high casein diet. It seemed that young rats were able to select a protein diet that supported maximal growth when proportions of dietary amino acids were balanced. It also seemed that the susceptibility of the rats to amino acid imbalance varied directly with the status of overall protein synthesis of the animals.
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PMID:Effects of amino acid imbalance and protein content of diets on food intake and preference of young, adult, and diabetic rats. 119 6

1. Phosphoenolpyruvate carboxykinase was assayed by three methods: (i) incorporation of H(14)CO(3) (-) into oxaloacetate: (ii) conversion of oxaloacetate into phosphoenolpyruvate, subsequently assayed enzymically; and (iii) transfer of (32)P from [gamma-(32)P]GTP to oxaloacetate. 2. Enzyme activity is increased in liver and epididymal adipose tissue in alloxan-diabetes and starvation, and in kidney in starved, acidotic and steroid-treated animals. 3. The ratios of the ;back' to the ;forward' reactions in liver, kidney and epididymal adipose tissue are different and characteristic of each tissue; they differ markedly from values reported for the purified mitochondrial enzyme. 4. The ratio of the ;back' to ;forward' reaction in any one tissue is constant in adrenalectomized, diabetic, acidotic and steroid-treated animals. 5. In starved animals, the ratio is increased in liver and kidney, but decreased in epididymal adipose tissue. 6. Administration of l-tryptophan results in an acute (1h) increase in activity measured in the ;forward' direction alone in liver and epididymal adipose tissue, but not in kidney.
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PMID:The activity of phosphoenolpyruvate carboxykinase in rat tissues. Assay techniques and effects of dietary and hormonal changes. 122 Jun 93

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

Water-soluble group B vitamins metabolism was studied over the course of streptozotocin-induced diabetes mellitus in rats fed semisynthetic isocaloric diets containing 18 and 50% of protein. A high-protein diet in diabetes mellitus does not influence riboflavin metabolism disordered in this disease but reduced 4-pyridoxyl acid excretion to the level characteristic of healthy animals. The observed trend to an increase of liver nicotinamide coenzymes levels and of 1-methylnicotinamide urinary excretion reflects increased niacin synthesis from the diet protein tryptophan, for niacin level is reduced in diabetes.
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PMID:[Effect of protein content in rat diet on water-soluble vitamin metabolism in streptozotocin-induced diabetes]. 130 52

1. The dynamic properties of erythrocyte membranes in diabetic children and of control erythrocyte membranes subjected to in vitro glycation have been investigated by means of fluorescence quenching of membrane tryptophan residues and ESR spectroscopy. 2. The apparent distance separating the membrane protein tryptophan and the bound 1-anilino-8-naphthalenesulphonate (ANS) molecules was decreased in erythrocyte membranes from children with diabetes. This resulted in a significant increase of the maximum energy transfer efficiency in diabetic membranes. 3. The relevant alterations occurred in the above parameters due to the in vitro nonenzymatic glycosylation of control membranes. 4. These changes were accompanied by the decreased hw/hs parameter of MSL and the increased relative rotational correlation time (tau c) of ISL in diabetic membranes and in the membranes subjected to in vitro glycation. 5. The results suggest that the conformational changes in membrane proteins may occur at both the intrinsic and exposed thiol groups. 6. Both the in vivo and the in vitro data indicate that nonenzymatic glycosylation of membrane proteins may be the major factor attributable to the alterations in the dynamic properties of erythrocyte membrane in diabetic state.
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PMID:Hyperglycaemia alters the physico-chemical properties of proteins in erythrocyte membranes of diabetic patients. 133 22

Water-soluble crystallins were obtained from clear human lenses of different age (4-81-year-olds) and lenses of individuals showing senile or diabetic cataracts. Levels of early glycation products were high in the high molecular weight material (HM) and the alpha-crystallin fractions, compared with beta- and gamma-crystallins. This difference becomes more prominent upon aging. The content of total early glycation products in HM and alpha-crystallin increases clearly with age, whereas levels remain relatively constant in the beta- and gamma-crystallins. There is an elevation of early products in cataractous lenses from diabetic individuals compared with those suffering from senile cataract. Specific non-tryptophan fluorescence (excitation/emission wavelengths 370/440 nm), used as an indicator for late glycation products, increased dramatically with age and was 2-fold higher in the diabetic subjects. Levels of fluorescence decreased in the order HM > alpha- > beta- > gamma-crystallins. The results suggest an increase in glycation rate in alpha-crystallin as a result of aging and diabetes, while the rate of glycation of beta- and gamma-crystallins remains almost constant.
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PMID:Glycation of crystallins in lenses from aging and diabetic individuals. 145 95

Nonenzymatic glycation has been found to increase in a variety of proteins in diabetic patients. The present study examined a possibility of preventing glycation and subsequent structural modifications of proteins by alpha-lipoic acid (thioctic acid) as lipoate, a substance which has gained attention as a potential therapeutic agent for diabetes-induced complications. Incubation of bovine serum albumin (BSA) at 2 mg/ml with glucose (500 mM) in a sterile condition at 37 degrees C for seven days caused glycation and structural modifications of BSA observed by SDS-PAGE, near UV absorption, tryptophan and nontryptophan fluorescence, and fluorescence of an extrinsic probe, TNS (6-(p-toluidinyl)naphthalene-2-sulfonate). When BSA and glucose were incubated in the presence of lipoate (20 mM), glycation and structural modifications of BSA were significantly prevented. Glycation and inactivation of lysozyme were also prevented by lipoate. These results suggest a potential for the therapeutic use of lipoic acid against diabetes-induced complications.
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PMID:Lipoate prevents glucose-induced protein modifications. 145 92

Glycation of crystallins and high molecular weight (HMW) aggregates was followed during aging (16-85 years) and in diabetes (44 and 70 years old). Lens soluble and insoluble fractions were reduced with [3H]NaBH4 and separated by molecular sieve HPLC. The protein content in each HPLC peak was measured by the Lowry method. The tritium incorporation, expressed as cpm mg-1 protein, was taken as a measure of early glycation and specific non-tryptophan fluorescence (Ex: 370 nm; Em: 440 nm), expressed as relative fluorescence U mg-1 protein, was taken as a measure of advanced glycation. The youngest lenses analysed were 16 and 17 years old and these provided the baseline values. The results showed that during aging there was about a three-fold increase in tritium incorporation and fluorescence of alpha-crystallin, while the increases in beta and gamma were only two-fold from the levels seen in 16- and 17-year-old lenses. On the other hand, both the soluble and insoluble HMW aggregate fractions showed up to five-fold increase in tritium incorporation during aging. The fluorescence was about two-fold higher in the insoluble HMW aggregates as compared to the soluble HMW aggregates in 16- and 17-year-old lenses and both showed an increase of about three-fold during aging. Diabetes resulted in an approximately 10-50% increase in tritium incorporation and non-tryptophan fluorescence of various crystallins and HMW aggregates.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glycation of human lens proteins: preferential glycation of alpha A subunits. 152 66

The effects of bound fatty acids and nonenzymatic glycosylation (NEG) on tryptophan binding to human serum albumin (HSA) were examined utilizing a rate of dialysis technique. HSA with 0, 1, 2, 3, or 5 mol of palmitate bound per mol of HSA was glycosylated in vitro to a level exceeding that seen in diabetes. NEG was not inhibited by fatty acids, suggesting that Lys-525, the primary site for NEG, is not an essential component of the principal sites for long-chain fatty acid binding to HSA. Scatchard analysis of binding data showed an expected fatty acid dependent decrease in the number of available tryptophan binding sites, but showed that fatty acids did not affect tryptophan affinity. The binding data failed to show an effect of NEG on tryptophan binding. The lack of inhibition of tryptophan binding by NEG suggests that drug-binding Site II, the indole/benzodiazepine site, is resistant to both NEG and to any conformational changes in HSA which may occur with NEG. These data suggest that elevated plasma free tryptophan and the resulting altered serotonin metabolism seen in diabetes are independent of increased NEG and likely result from diabetic hyperlipidemia.
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PMID:Effects of nonenzymatic glycosylation and fatty acids on tryptophan binding to human serum albumin. 157 75


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