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 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

A Danish data source was examined to determine age and sex specific rates of diabetes and glaucoma in a large cataract extracted population. Comparisons with population rates were done. An excess prevalence of diabetes in the cataract population below 70 years was found. For cataract extracted males and females below the age of 40 years, the diabetes prevalence was 15 to 25 times the prevalence in a general population. This prevalence excess decreases with age to normal levels at 75 years of age. Furthermore, we found higher relative frequencies of diabetes among cataract extracted females than among males. Mean age at time of surgery was significantly lower for the diabetic cataract patients. Also for primary glaucoma, an excess prevalence was found in the cataract population. For cataract extracted males and females aged 40 to 49 years the glaucoma frequency was 4-5 times the frequency in a general population. This excess relative frequency decreases with age. The glaucomatous cataract patients have a higher mean age at the time of cataract surgery. A large number of factors seems to contribute to the excess frequencies of diabetes and glaucoma found in the cataract extracted population.
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PMID:Epidemiologic aspects of cataract surgery. III: Frequencies of diabetes and glaucoma in a cataract population. 662 7

The clinical and electro-neurographic examinations were carried out in 54 patients aged 21-67 years (mean = 41.8) with IDDM of at least 10-year duration, and 25 subjects aged 19-62 years (mean = 39.0) as a control group. The aim of the study was the determination of: 1) the frequency of polyneuropathy appearance in patients with IDDM of at least 10-year duration; 2) the usefulness of electroneurography for detection of subclinical impairment of peripheral nervous system in diabetics; 3) the characterization of electro-neurographic abnormalities in diabetic neuropathy; 4) the influence of diabetes duration and metabolic control on severity of peripheral nerves affection; 5) the relationship between polyneuropathy and retinopathy, nephropathy and cataract occurrence in diabetic patients. Polyneuropathy was diagnosed--clinically in 67% of patients, electro-neurographically in 85% of patients. The neurographic study proved high sensitivity for detection of subclinical affection of peripheral nerves in diabetics. The electro-neurographic abnormalities appeared more frequently and were more considerable in the group of patients with clinical polyneuropathy. Frequency of the sensory and motor nerve fibres involvement was similar. The electroneurographical abnormalities corresponded with the features of mixed--axonal and demyelinating type of neuropathy. It was disclosed that the degree of neurographical changes did not depend on duration and severity of hyperglycemia in late period of the disease. A moderate relationship between occurrence of polyneuropathy and retinopathy, nephropathy as well as diabetic cataract was revealed.
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PMID:[Clinical and electroneurographic changes in the peripheral nervous system of patients with chronic insulin-dependent diabetes (IDDM)]. 750 45

The etiology of diabetic cataract is usually explained by the following process; the conversion of glucose and galactose to polyol by aldose reductase, then the accumulation of polyol in lens, and the opacity of lens. Another explanation is that the hyperoxidation of lens membrane due to an increase of active oxygen and lipid peroxide in lens induces diabetic cataract. The experimental animals used in the present study were rats with galactose cataract and streptozotocin cataract. We measured the levels of antioxidants (glutathione, ascorbic acid) and lipid peroxide (malonodialdehyde) in lens, aqueous humor and vitreous body. Furthermore we studied the effects of aldose reductase inhibitor (TAT) on these levels. In streptozotocin diabetes rats, the increased malonodialdehyde levels in lens, aqueous humor and serum were suppressed by TAT administration. In galactose and streptozotocin diabetes rats, the decreased levels of glutathione and ascorbic acid were suppressed by TAT administration.
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PMID:[Biochemical changes in lens, aqueous humor and vitreous body and effects of aldose reductase inhibitor (TAT) on rats with experimental diabetes]. 755 22

To evaluate accumulation of advanced glycation end-products (AGE) in diabetes and its possible correlation with late diabetic complications, AGE levels were measured by spectrofluorimetry in eye lens and sciatic nerve proteins and isolated tail tendon collagen of rats with experimental diabetes of 3- and 6-month duration. The values obtained were compared to those from age-matched control rats and correlated with cataract presence and somatosensory evoked potential (SEP) alterations. Diabetic animals had increased AGE levels in all tissues at both times; cataract developed in 29% of diabetic rats at 3 months and in 57% at 6 months; SEP conduction velocity was reduced in diabetic animals both at 3 (54.5 +/- 1.8 S.E.M. m/s vs. 73.9 +/- 1.0, P < 0.0001) and 6 months (59.5 +/- 1.4 vs. 71.5 +/- 1.6, P < 0.0001) from diabetes induction. No eye lens AGE level differences were observed when cataract presence was considered. Interestingly, in diabetic rats, increased sciatic nerve AGE levels were associated with reduced SEP. These data show that: (1) AGE levels are increased as early as 3 months from development of hyperglycemia; (2) other factors, in addition to an enhanced rate of fluorescent AGE formation, might play important roles in the pathogenesis of diabetic cataract; (3) increased peripheral nerve AGE levels are associated with SEP alterations.
Diabetes Res Clin Pract 1995 Apr
PMID:Role of advanced glycation end-products (AGE) in late diabetic complications. 758 17

This paper reviews the changes which occur in the human lens in diabetes. They include refractive changes and cataract and age-related increases in thickness, curvatures, light scattering, autofluorescence and yellowing. The incidence of cataract is greatly increased over the age of 50 years, slightly more so in women, compared with non-diabetics. Experimental models of sugar cataract provide some evidence for the mechanism of the uncommon, but morphologically distinct, juvenile form of human diabetic cataract, where an osmotic mechanism due to sugar alcohol accumulation has been thoroughly studied in diabetic or galactose-fed rats. The discrepancy between the ready accumulation of sugar alcohol in the lens in model systems and the very slow kinetics of aldose reductase (AR) has not been satisfactorily explained and suggests that the mechanism of polyol formation is not yet fully understood in mammalian systems. The activity of AR in the human lens lies mainly in the epithelium and there appears to be a marginal expectation that sufficient sorbitol accumulates in cortical lens fibres to explain the lens swelling and cataract on an osmotic basis. This is even more so in the cataracts of adult diabetics, which resemble those of age-related non-diabetic cataracts in appearance. The very low levels of sorbitol in adult diabetic lenses make an osmotic mechanism for the increased risk of cataract even less likely. Other mechanisms, including glycation and oxidative stress, are discussed. The occurrence of cataract is a predictor for increased mortality in the diabetic.
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PMID:The lens in diabetes. 760 46

Experimental work in our laboratory has confirmed the protective activity of vanadium compounds on hyperglycemia and glycosuria in streptozotocin (STZ) diabetes. Furthermore, diabetic cataract has also been partially prevented. Nevertheless, the combination of a natural antioxidant, vitamin E, with Na3 VO4 has not further enhanced this ameliorating effect. Our experimental approach has been an attempt to block the prooxidant activity of both STZ and vanadate, with the purpose of eliciting the best possible antidiabetic protection. More recently, a lipid soluble synthetic antioxidant U-78517F, a 2-methylaminochroman, has been reported to have a significant protective effect against brain injury and ischemia. This compound inhibits the iron-dependent lipid peroxidation 100 times more effectively than vitamin E. This investigation has introduced a combination of the vanadium compound plus the aforesaid lazaroid, as its (-) enantiomer, U-83836E, in order to improve the insufficient protection when vitamin E was used. For twelve weeks, male Wistar rats, rendered diabetic with STZ, were administered Na3VO4 in drinking water along with the lazaroid carried by the food. Four, eight and twelve weeks after the beginning of the protective treatment, fluid and food intake, diuresis and excreted feces, glycosuria and proteinuria were determined on biological samples obtained in metabolic cages; body weight and glycemia were also recorded. At weeks 6 and 12 of the treatment, the opaqueness of the eye lenses was controlled and registered. At the end of the experiment, circulating glycosylated hemoglobin (HbA1c), fructosamine, N-acetyl-beta-D-glucosaminidase (NAG), and fluorescent peroxides were evaluated. Within the first month of treatment, protection by the combination paralleled that elicited by vanadate alone. At subsequent steps, U-83836E significantly improved the protective effect of vanadate alone on polydipsia and polyuria, but especially on hyperglycemia and glycosuria. The further ameliorating effect of the lazaroid was also observed on HbA1c and NAG, and, most important, on the cataract. In conclusion, these findings demonstrate that the lazaroid U-83836E succeeds in further protecting the most important symptoms of diabetes treated with vanadate, and that this antioxidant acts effectively even when it is administered orally in food, in a non invasive manner.
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PMID:Amelioration of diabetes and cataract by Na3VO4 plus U-83836E in streptozotocin treated rats. 782 6

Diabetic lens glucose metabolism in vivo can be altered by a number of exogenous substrates. We have chosen two, one a glucose epimer (mannose) and the other a glycolytic intermediate (pyruvate), to demonstrate the possibility of this approach. D(+)-Mannose is a D(+)-glucose epimer but in lenses incubated in 35.5 mM mannose, no mannitol (the sorbitol equivalent) was detected, while both lactate production and 31P profile appeared normal. Mannose therefore is a good glucose substitute causing no polyol formation. Mannose metabolism in the rat lens in vivo was then examined. Diabetic rats fed mannose-enriched diet over a period of 14 days showed retardation of changes in 31P metabolites, specifically the levels of phosphorylcholine and glycerophosphorylcholine, suggesting a protective effect. Rat lenses incubated in 35.5 mM glucose in the presence of 5 mM pyruvate (pyr) showed 50% lower sorbitol than without pyr. With 5 mM pyr in the drinking water, i.e. pretreatment in vivo during a 3-day diabetes induction period, the diabetic rat lens accumulated acetate and alanine when incubated in the presence of pyr. The decrease in sorbitol was most likely due to a lower glucose flux rather than an increased polyol dehydrogenase activity. Increasing glucose concentration from 5.5 to 35.5 mM or provision of exogenous pyr both caused an intermediate increase in O2 consumption in the normal lens; a maximal activity was reached with both 35.5 mM glucose and 5 mM pyruvate in the incubating medium. In the diabetic lens, O2 consumption could reach the intermediate but not the maximal level. Dietary pyr pre-treatment also prevented normal and diabetic lenses from maximal pyr-stimulated O2 consumption. The NMR and O2 consumption data together indicated activation of alanine dehydrogenase and saturation of Krebs cycle. It appears that dietary supplement of mannose can preserve 31P membrane metabolites in the diabetic lens. Mannose can be used in conjunction with hypoglycemic therapy for the management of diabetic cataract. In addition, pyruvate may be effective in enhancing lens energy metabolism and lower sorbitol production.
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PMID:Manipulating rat lens glucose metabolism with exogenous substrates. 854 89

Oxidative stress has recently been involved in a number of diseases including development of diabetic cataract. If hyperglycemia is the relevant factor in diabetes, then it is reasonable to assume that under physiological conditions glucose may be toxic. The mechanisms involved in such a type of glucose 'toxicity' are still poorly understood but may involve glucose autoxidation. In this study we discuss a new methodological approach to the evaluation of glucose-induced oxidative damage to bovine lens membranes. The method is based on the incorporation of a fluorescent probe (parinaric acid) into lens membranes. The oxidative degradation of the probe is evaluated by monitoring its fluorescence decrease. It was possible to show that glucose may induce oxidative damage in the presence of trace amounts of transition metals. Furthermore, the data obtained by monitoring oxidative degradation of parinaric acid could be related to the amount of thiobarbituric acid-reactive substances formed under identical periods of time. The technique was shown to be reproducible, straightforward and highly sensitive as compared to other classical methods. Moreover, this methodological approach allows not only the evaluation of the extension of oxidative stress inflicted upon lens membranes but also the evaluation of the antioxidant effect of various compounds including some drugs with a potential anticataractogenic effect.
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PMID:A technical approach to the evaluation of glucose oxidation: implications for diabetic cataract. 897 75

Experimental work from our laboratory has confirmed the protective power of vanadium compounds on hyperglycemia and glycosuria in streptozotocin (STZ) diabetes. Furthermore, the diabetic cataract too has been partially prevented. The protection slightly increased, when vanadium was administered in combination with vitamin E. This investigation has introduced a combination of Na3VO4 plus the lazaroid U-83836E, a liposoluble antioxidant much more efficacious than tocopherol, in order to improve the insufficient protection when vitamin E was used. Male Wistar rats, rendered diabetic with STZ, were treated for 12 weeks with Na3VO4 in drinking water, U-83836E carried by the food, or both. The most significant metabolic parameters (food and fluid intake, diuresis and excreted feces) were studied monthly by means of metabolic cages. Body weight, glycemia, glycosuria and proteinuria were also recorded. At week 6 and 12 of the treatment, the opaqueness of the eye lenses was controlled. Circulation glycosylated hemoglobin (HbA1c), fructosamine, N-acetyl-beta-D-glucosaminidase (NAG) and fluorescent peroxides were evaluated at the end of the experiment. After the first month of treatment U-83836E improved significantly the protective effect of vanadate alone on polydipsia and polyuria, but more efficiently on hyperglycemia and glycosuria. The further ameliorating effect of the lazaroid was observed also on HbA1c, NAG and, most important, on the cataract. In conclusion, these findings demonstrate that the lazaroid U-83836E succeeds in further protecting the most important symptoms of diabetes treated with vanadate, and that this antioxidant acts effectively even when it is administered per os, in a non invasive manner.
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PMID:[Protective effect on nephropathy and on cataract in the streptozotocin-diabetic rat of the vanadium-lazaroid combination]. 899 28


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