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)

Normal and streptozotocin diabetic female Wistar rats were given vitamin E in the diet as the tocopherol, acetate, or succinate form (2,850 IU/kg food). At the end of 6 weeks, the rats were examined for weight gain or loss, general body condition, and cataracts. At sacrifice, blood was collected for measurement of serum glucose, and gamma-crystallin levels were measured in aqueous and vitreous humors using a radioimmunoassay. One lens was homogenized in 8 M guanidinium chloride for ATP analysis. In normal rats, gamma-crystallin was detected in both aqueous and vitreous humors, with the higher concentration in the vitreous humor. Diabetes caused a sixfold increase in gamma-crystallin in both the aqueous and vitreous humors. Diabetes also led to a significant worsening in general body condition, loss of body weight, formation of cataracts, and decrease in lens ATP levels. Addition of vitamin E and vitamin E succinate, but not vitamin E acetate, to the diet resulted in reduction of gamma-crystallin leakage into the vitreous humors and an increase in body weight. There was no improvement noted for the lens ATP levels, the general body condition, or visual cataract score. Neither streptozotocin-induced diabetes nor vitamin E in the diet appeared to affect the weight of the lenses.
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PMID:Modeling cortical cataractogenesis: IX. Activity of vitamin E and esters in preventing cataracts and gamma-crystallin leakage from lenses in diabetic rats. 262 5

Cataract is a long-term complication of diabetes mellitus. Diabetics have increased glucosamine levels and it is possible that the non-enzymic glycosylation of the lens structural proteins by glucosamine induces conformational changes in the lens that contribute to cataract formation. Aspirin and aspirin-like analgesics may protect against glycosylation. In this paper the binding of glucosamine to bovine lens proteins and the effects of aspirin, paracetamol and ibuprofen on this reaction were investigated. Significant binding of glucosamine to the lens proteins was found. Gel-chromatography indicated that beta H-crystallin was most reactive to the amino-sugar. Of the analgesics studied, aspirin was the most effective inhibitor of glycosylation, followed by the other anti-inflammatory drug, ibuprofen. Preincubation of the lens homogenate with aspirin was no more effective at decreasing binding of glucosamine than was simultaneous incubation with aspirin. Glutathione significantly inhibited glucosamine binding. Glucosamine is active in non-enzymic glycosylation but the reaction can be inhibited by agents thought to protect against cataract.
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PMID:The non-enzymic glycosylation of bovine lens proteins by glucosamine and its inhibition by aspirin, ibuprofen and glutathione. 275 89

The incorporation of 14C-glucose in native pig lens crystallins by in vitro incubation was found, after subsequent dialysis, to affect all five classes of crystallin separated by Sepharose CL-6B chromatography, but four times more radioactivity appeared in the alpha-H fraction than in any of the others (14.25 vs 3.16, 3.25, 1.69 and 2.30 kCPM/mg for alpha-H, alpha-L, beta-H, beta-L and gamma crystallins respectively). The autoradiographs of one- and two-dimensional electrophoresis patterns nevertheless showed the total radioactivity to be quite evenly distributed among the various subunits of the proteins; the alpha-H subunits did not exhibit a markedly greater affinity for glucose than the others. The high levels of stable glycation products in the alpha-H fraction are therefore attributed to the fraction's increasing during glycation rather than to its components being especially susceptible to glycation. This finding is interpreted as supporting the glycation-originated protein hyper-aggregation theory of the pathogenesis of diabetic cataract.
Diabetes Res 1988 Aug
PMID:The stable products of the non-enzymatic glycation of pig crystallins: new findings related to the pathogenesis of diabetic cataracts. 323 79

Radioactive galactose becomes attached covalently to lens proteins in the same way as glucose. Simultaneous incubation with aspirin inhibits the reaction with galactose in a dose-related manner. Incubation with aspirin before incubation with galactose in the absence of aspirin showed that aspirin can modify crystallins permanently to prevent the binding of galactose. The galactosylation was also inhibited by glutathione at physiological concentrations. All major groups of lens proteins reacted with galactose but a higher level of modification of protein in the material of high molecular weight may indicate that galactosylation has induced aggregation of the proteins. The modification of all major crystallin groups was confirmed by isolating the galactosylated proteins by affinity chromatography. The results are discussed in relation to glycosylation of lens proteins in diabetes and galactosaemia and the role of glycosylation in cataract.
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PMID:Non-enzymic glycosylation (glycation) of lens proteins by galactose and protection by aspirin and reduced glutathione. 340 87

Because of their remarkable longevity, lens crystallins undergo a substantial amount of glycation (non-enzymatic glycosylation) during diabetic hyperglycemia. These post-translational modifications have the potential to disrupt the structural and functional properties of the lens crystallins and contribute to the formation of cataracts. Streptozotocin-induced diabetic rats were used to study the relationship between glycation of lens proteins and the formation of insoluble high-molecular-weight (HMW) aggregates believed to be responsible for cataract formation. After the onset of diabetes, cataracts developed in about 12- to 13 weeks. The animals were followed in this manner until cataracts developed and for an additional 63 days. Five control and five diabetic rats were killed every 3 weeks and lenses removed. Levels of glycated protein and glycated amino acids in lenses from each animal were examined by affinity chromatography. In addition, the changes in crystallin composition and development of HMW aggregates were monitored by molecular-sieve HPLC techniques. As diabetic hyperglycemia continued there was a linear increase in glycated protein in both the soluble and insoluble fractions. This increase was paralleled by an increase in the soluble HMW and insoluble HMW aggregates. Other changes included a decrease in reactive sulfhydryls which indicates an increase in disulfide bond formation. The gamma-crystallin levels also decreased in a linear fashion during the hyperglycemic pre-cataract and cataract stages. It appears that the glycation of lens crystallin, the disappearance of reactive sulfhydryls and the formation of HMW aggregates are interrelated.
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PMID:Progressive changes in lens crystallin glycation and high-molecular-weight aggregate formation leading to cataract development in streptozotocin-diabetic rats. 358 12

Lens crystallins undergo non-enzymatic glycosylation with aging and diabetes mellitus. It is not known, however, whether all crystallins are subject to the same extent of glycosylation. Human diabetic lenses (approximately 80 years of age) were dissected into cortex and nucleus, then fractionated into various crystallins with gel chromatography (Sephacryl S-200, Sephadex G-75 or Bio Gel A-15m). The glycosylated crystallins were then separated from the nonglycosylated crystallins by affinity chromatography on Glyco Gel B boronic acid. The percentage of glycosylated crystallin was about 20-30%, and did not differ much among most crystallins, although gamma-crystallin has significantly less (p less than 0.01) glycosylated protein. The extent of glycosylation in the glycosylated crystallins, however, was found to be greater in the high molecular weight crystallins. The extent of glycosylation in alpha-crystallins is approximately two to four times that observed in beta- or gamma-crystallin. The extent of glycosylation appears to depend not only on the lysine content, which does not vary much among the crystallins, but also on the accessibility of the surface areas where lysine residues are located. This accessibility depends on the protein conformation and appears to correlate with protein unfolding.
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PMID:Non-enzymatic glycosylation in human diabetic lens crystallins. 371 14

Normal and streptozotocin diabetic female Wistar rats were given butylated hydroxytoluene at 0-, 0.067- or 0.50% w/w in the diet. At the end of 10 weeks, the animals were examined for weight gain or loss, general body condition, and cataracts. After death, blood was collected for measurement of serum glucose. gamma-Crystallin was determined in aqueous and vitreous humours using a radioimmunoassay. One lens from each rat was homogenized in 8 M guanidinium chloride for adenosine triphosphate analysis. In normal rats, there is a small amount of gamma-crystallin found in the vitreous humour, and an even smaller amount in the aqueous humour. Diabetes caused a 2.5-fold increase of gamma-crystallin in the aqueous humour and a five-fold increase in the vitreous humour. Diabetes also led to a significant worsening in general body condition, loss of body weight, decrease in lens adenosine triphosphate levels, and formation of cataracts. Addition of butylated hydroxytoluene (BHT) to the diet resulted in improved general body condition, reduction in cataracts, decrease of gamma-crystallin leakage into the vitreous humour, and weight gain. There was no effect of dietary butylated hydroxytoluene on levels of lens adenosine triphosphate. Neither the diabetic state nor treatment with butylated hydroxytoluene affected the weight of the lenses.
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PMID:Modelling cortical cataractogenesis VIII: effects of butylated hydroxytoluene (BHT) in reducing protein leakage from lenses in diabetic rats. 378 Aug 76

The effect of streptozocin diabetes of 14 days duration on the integrity of lenticular crystallins has been determined by the measurement of characteristic markers of protein modification in the lens crystallins of rats. Further, the susceptibility of the crystallins to modification has also been determined by measurement of the same markers after the application of a metal-catalyzed oxidative insult in vitro. The results show that the previously reported increased post-translational modification of lens crystallins in vivo and increased susceptibility to modification in vitro of diabetic crystallins after 21 days of uncontrolled diabetes are also evident after just 14 days of diabetes. Treatment of the diabetic animals with the antioxidant ubiquinone by dietary supplementation was unable to prevent the post-translational modifications sustained by the crystallin when subjected to diabetes in vivo or the increase in susceptibility to an in vitro oxidative stress. While the present results support the proposal that cataract formation is initiated by protein post-translational modification factors such as glycation, ubiquinone supplementation does not appear to be beneficial in the inhibition of post-translational crystallin modification in diabetic cataractogenesis.
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PMID:Effect of diabetes and dietary ubiquinone supplementation on the post-translational modification of rat lens beta L crystallin. 758 76

In vitro glycation was previously shown to influence alpha-crystallin chaperone function. In the present study we show that this function is compromised in diabetes. The alpha H, alpha L and the total alpha fractions were isolated by gel permeation chromatography from the water-soluble protein of streptozotocin-diabetic as well as age-matched normal rats. Based on the beta L-crystallin thermal denaturation assay the chaperone function was significantly decreased in the diabetic rats.
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PMID:Diabetes affects alpha-crystallin chaperone function. 761 5

Methylglyoxal is an endogenous metabolite that increases in diabetes and has been implicated in some of its long-term complications such as retinopathy, neuropathy and cataract. We investigated the reaction of methylglyoxal with isolated human and bovine lens crystallins (alpha, beta H, beta L and gamma). After 7 days incubation at 37 degrees C and pH 6.9, the reaction of methylglyoxal with lens proteins yielded stable adducts that exhibited fluorescent properties. SDS-polyacrylamide gel electrophoresis was used to monitor aggregation and crosslinking of the modified protein and autoradiography showed that [14C]methylglyoxal was incorporated into all the protein bands. Bovine gamma-crystallin was the most reactive towards methylglyoxal. Reaction of methylglyoxal with bovine gamma II-crystallin, which is found mainly in the lens nucleus, could alter the change surface network of the molecule, resulting in aggregation, increased light scattering and hence cataract. Modification of gamma II-crystallin by methylglyoxal produced an overall loss of positive charge and an increase in molecular weight and non-disulfide covalent crosslinking. Amino acid analysis of the modified gamma II-crystallin showed a loss of 47% of arginine residues.
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PMID:The reaction of methylglyoxal with human and bovine lens proteins. 782 33


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