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Journal ArticleDOI

Ascorbic acid metabolism in diabetes mellitus

TL;DR: Ascorbic acid supplementation at a dose of 500 mg per day for a brief period of 15 days resulted in an increase in the plasma ascorbate level temporarily, but it did not lower the blood glucose level of the diabetic patients.
Abstract: In contrast to normal subjects diabetic patients and very low plasma ascorbic acid and significantly high (p less than 0.001) dehydroascorbic acid irrespective of age, sex, duration of the disease, type of treatment, and glycemic control. However, there was no significant difference between the mean leukocyte ascorbate concentrations of the two populations. The in vitro rates of dehydroascorbate reduction in the hemolysate and the erythrocyte reduced glutathione levels and the glucose-6-phosphate dehydrogenase activities, which regulate the dehydroascorbate reduction, were similar in normal and diabetic subjects. The turnover of ascorbic acid was higher in the diabetics than that in the normal volunteers. Experiments with diabetic rats indicated that the increased turnover of ascorbic acid was probably due to increased oxidation of ascorbate to dehydroascorbate in tissue mitochondria. Ascorbic acid supplementation at a dose of 500 mg per day for a brief period of 15 days resulted in an increase in the plasma ascorbate level temporarily, but it did not lower the blood glucose level of the diabetic patients.
Citations
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Journal ArticleDOI
TL;DR: Overall, studies of glycation and protein browning suggest a critical role for oxidative processes perhaps involving decompartmentalized transition metals and a variety of low molecular weight reducing agents in diabetes mellitus and ageing.

926 citations

Journal ArticleDOI
01 Nov 1990-Diabetes
TL;DR: The studies indicate that glycosylation and peroxidation occur concomitantly in LDL modified by glucose in vitro and may both contribute to the behavioral changes of this lipoprotein.
Abstract: It has been postulated that the etiology of the complications of diabetes involves oxidative stress, perhaps as a result of hyperglycemia. Consistent with this hypothesis, it has been shown that glucose, under physiological conditions, produces oxidants that possess reactivity similar to the hydroxyl free radical. These oxidants hydroxylate benzoic acid, fragment protein, and induce peroxidation in phosphatidylcholine liposomes and low-density lipoprotein (LDL) when LDL is incubated with hyperglycemic levels of glucose in vitro. These reactions are accelerated by transition metals and inhibited by a metal-chelating agent. The atherosclerotic potential of LDL in diabetes mellitus is often discussed in terms of protein glycosylation, which may affect cellular interactions. Our studies demonstrate, however, that peroxidative reactions also accompany LDL glycosylation in vitro. Peroxidative modification of LDL has also been implicated in LDL atherogenicity. Our studies indicate that glycosylation and peroxidation occur concomitantly in LDL modified by glucose in vitro and may both contribute to the behavioral changes of this lipoprotein.

619 citations


Cites background from "Ascorbic acid metabolism in diabete..."

  • ...Antioxidants such as ascorbic acid, vitamin E, uric acid, and glutathione are all decreased in diabetes (1-4)....

    [...]

  • ...changes appear to be greater in those individuals displaying diabetic complications (2-7)....

    [...]

Journal ArticleDOI
TL;DR: Ascorbic acid is discussed in detail, and an analysis is made of whether it has the properties mentioned, and several water‐soluble candidates are mentioned, with most having no more than one or two of the attributes listed.
Abstract: Reactive free radical species (R.) are associated with several forms of tissue damage and disease, and also with the process of aging. Protection is thought to be available in the form of endogenous compounds that react with and thereby "scavenge" the R.. Because many R. are reactive forms of oxygen, an effective scavenger is often referred to as an antioxidant. To be an effective antioxidant physiologically, a substance must have certain chemical and biological properties: it must be present in adequate amounts in the body; it must react with a variety of R.; it must be suitable for compartmentation; it must be readily available; it might be suitable for regeneration; it must be conserved by the kidneys; and it must have tolerable toxicity. Several water-soluble candidates are mentioned, with most having no more than one or two of the attributes listed. Ascorbic acid is discussed in detail, and an analysis is made of whether it has the properties mentioned.

458 citations

Journal ArticleDOI
TL;DR: GLUT1 and GLUT3 isoforms are the specific glucose transporter isoforms which mediate DHA transport and subsequent accumulation of AA according to Xenopus laevis oocyte expression system studies.

431 citations

Journal ArticleDOI
TL;DR: It is shown that diabetic patients have significant defects of antioxidant protection, which may increase vulnerability to oxidative damage and the development of diabetic complications.
Abstract: Oxidative damage by free radicals has been implicated in the pathogenesis of vascular disease in diabetes. We compared the radical-scavenging antioxidant activity of serum from 28 patients with insulin-dependent diabetes mellitus and 24 patients with non-insulin-dependent diabetes mellitus uncomplicated by vascular disease with age-matched non-diabetic control subjects. Patients with insulin-dependent diabetes had significantly reduced total antioxidant activity (320.2 +/- 11.3 vs. 427.5 +/- 19.2 mumol L-1; P < 0.001). This was attributable to lower urate (209.4 +/- 10.4 vs. 297.1 +/- 16.7 mumol L-1; P < 0.001) and vitamin C levels (63.6 +/- 6.0 vs. 87.5 +/- 4.9 mumol L-1; P < 0.01). Patients with non-insulin-dependent diabetes had lower total antioxidant activity than age-matched control subjects (433.8 +/- 25.4 vs. 473.9 +/- 30.2 mumol L-1; NS), reflecting lower urate (299.5 +/- 19.4 vs. 324.8 +/- 21.4 mumol L-1; NS) and vitamin C levels (38.6 +/- 5.7 vs. 58.5 +/- 5.3 mumol L-1; P < 0.05). Multiple regression analysis showed that urate, vitamin C and vitamin E were the major contributors to serum total antioxidant activity. These results show that diabetic patients have significant defects of antioxidant protection, which may increase vulnerability to oxidative damage and the development of diabetic complications.

423 citations

References
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Journal ArticleDOI
D. Hornig1
TL;DR: The availability of labeled AA, metabolites, and analogues has made it possible to follow up the appearance of these compounds or mctabolites thereof in various tissues of animals by means of dissecting the animals with subsequent determination of the radioactive material accumulated by the tissues or by Means of whole-body autoradiography.
Abstract: One of the earliest attempts to gauge the involvement of ascorbic acid (AA) in the overall metabolism was thc determination of its distribution in thc tissues. A thorough knowledge of its occurrence was believed to be pertinent to the elucidation of the physiological role of the vitamin in the organism. The availability of labeled AA, metabolites, and analogues has made it possible to follow up the appearance of these compounds or mctabolites thereof in thc various tissues of animals by means of dissecting the animals with subsequent determination of the radioactive material accumulated by the tissues or by means of whole-body autoradiography, as described in detail by Kalberer.'

417 citations

Journal ArticleDOI
TL;DR: The chemical properties of these two substances are strikingly similar and it would appear logical to expect that there might be a relationship between alloxan and dehydroascorbic acid with regard to the production of diabetes.

109 citations