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)

Vitamin C (ASC) is well known as an outstanding antioxidant in animal tissues. This concept is reviewed from a chemical standpoint, starting from a chemical view of radical reactions in the cell. ASC, vitamin E, and lipid hydroperoxide were selected as key molecules involved in radical reactions in the cell, and their efficiencies as an index of oxidative stress were evaluated. At first, methods for specific and sensitive determination of ASC and lipid hydroperoxide were developed. Based on comparisons of these indices during oxidative stress in typical pathological conditions, such as diabetes and liver damage by toxicants, ASC concentration was found to be the most sensitive index in animal tissues. Antioxidative effect of food factors in vivo can be evaluated on the basis of these indices. Analysis of oxidation of low-density lipoprotein (LDL) revealed that degradation and cross-link of apolipoprotein B-100 (apoB) are extremely facile processes. Fragmented and conjugated apoB proteins are present in normal human serum, and tend to increase with age based on immunoblot analysis. Estimation of these products allows us a mechanism-based diagnosis of atherosclerosis. A significant relationship between plasma ASC level and the sum of these apoB products was found. In conclusion, specifically determined ASC concentration sensitively reflects oxidative stress in tissues.
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PMID:Vitamin C: basic metabolism and its function as an index of oxidative stress. 1507 65

In this study, we clarify that high glucose inhibits albumin uptake in cultured LLC-PK1 cells. LLC-PK1 cells cultured for 6 days with 5.5-27.8 mM D-glucose were challenged by fluorescein isothiocyanate (FITC)-conjugated human albumin (HA). FITC-HA binding and uptake were inhibited by >5.5mM glucose (5.5 mM > (P < 0.01) 11.0 mM > (P < 0.05) 16.7 mM approximately= 27.8 mM). Analysis of FITC-HA binding and uptake at 5.5 and 16.7 mM D-glucose (high glucose, HG) showed decreased affinity (K(m) for binding: 35.5 mg/l versus 52.6 mg/l, K(m) for uptake; 41.3 mg/l versus 55.6 mg/l) and maximal velocity (B(max)--0.33 microg versus 0.27 microg/30 min/mg protein; U(max)--4.40 microg versus 3.48 microg/60 min/mg protein) at HG. A comparison of the time courses of FITC-HA binding and uptake at 5.5 mM glucose and at HG showed that HG suppressed them beyond 15 min (P < 0.005-0.001). Phlorizin (>0.25 mM) completely reversed the HG-induced inhibition of FITC-HA binding and uptake. High glucose decreased mRNA of GLUT-1 and SGLT-1, but did not influence that of SGLT-2. The simultaneous presence of Vitamin E (10(-6)M), Vitamin C (10(-6)M) and reduced glutathione (0.25 mM) reversed the suppressed FITC-HA binding and uptake by HG, while any one or two of these molecules, and various inhibitors of advanced glycation end products, failed to do so. In conclusion, a high glucose milieu causes inhibition of albumin binding and uptake in proximal tubular cells by increasing metabolic oxidative stress through excessive glucose flux via the sodium glucose transporter.
Diabetes Res Clin Pract 2004 Sep
PMID:High glucose reduces albumin uptake in cultured proximal tubular cells (LLC-PK1). 1533 Dec 1

Ascorbic acid is necessary for optimal insulin secretion from pancreatic islets. We evaluated ascorbate recycling and whether it is impaired by increased glucose metabolism in the rat beta-cell line INS-1. INS-1 cells, engineered with the potential for overexpression of glucokinase under the control of a tetracycline-inducible gene expression system, took up and reduced dehydroascorbic acid to ascorbate in a concentration-dependent manner that was optimal in the presence of physiologic D-glucose concentrations. Ascorbate uptake did not affect intracellular GSH concentrations. Whereas depletion of GSH in culture to levels about 25% of normal also did not affect the ability of the cells to reduce dehydroascorbic acid, more severe acute GSH depletion to less than 10% of normal levels did impair dehydroascorbic acid reduction. Culture of inducible cells in 11.8 mM D-glucose and doxycycline for 48 h enhanced glucokinase activity, increased glucose utilization, abolished D-glucose-dependent insulin secretion, and increased generation of reactive oxygen species. The latter may have contributed to subsequent decreases in the ability of the cells both to maintain intracellular ascorbate and to recycle it from dehydroascorbic acid. Cultured beta cells have a high capacity to recycle ascorbate, but this is sensitive to oxidant stress generated by increased glucose metabolism due to culture in high glucose concentrations and increased glucokinase expression. Impaired ascorbate recycling as a result of increased glucose metabolism may have implications for the role of ascorbate in insulin secretion in diabetes mellitus and may partially explain glucose toxicity in beta cells.
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PMID:Ascorbic acid recycling by cultured beta cells: effects of increased glucose metabolism. 1547 12

It has been estimated that 30-40 percent of all cancers can be prevented by lifestyle and dietary measures alone. Obesity, nutrient sparse foods such as concentrated sugars and refined flour products that contribute to impaired glucose metabolism (which leads to diabetes), low fiber intake, consumption of red meat, and imbalance of omega 3 and omega 6 fats all contribute to excess cancer risk. Intake of flax seed, especially its lignan fraction, and abundant portions of fruits and vegetables will lower cancer risk. Allium and cruciferous vegetables are especially beneficial, with broccoli sprouts being the densest source of sulforophane. Protective elements in a cancer prevention diet include selenium, folic acid, vitamin B-12, vitamin D, chlorophyll, and antioxidants such as the carotenoids (alpha-carotene, beta-carotene, lycopene, lutein, cryptoxanthin). Ascorbic acid has limited benefits orally, but could be very beneficial intravenously. Supplementary use of oral digestive enzymes and probiotics also has merit as anticancer dietary measures. When a diet is compiled according to the guidelines here it is likely that there would be at least a 60-70 percent decrease in breast, colorectal, and prostate cancers, and even a 40-50 percent decrease in lung cancer, along with similar reductions in cancers at other sites. Such a diet would be conducive to preventing cancer and would favor recovery from cancer as well.
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PMID:Nutrition and cancer: a review of the evidence for an anti-cancer diet. 1549 24

Hyperinduced oxidant stress may have a role in the pathogenesis of diabetes and its micro- and macrovascular complications. Attaining euglycemia and the use of antioxidant vitamins could reduce oxidant stress and complications. In general, evidence does not support the use of supplements, and supplements are not recommended unless patients are deficient. Use of vitamins in excess may have adverse effects. Vitamin supplements are indicated in patients deficient in vitamins due to inadequate dietary intake or intestinal disease. Treatment with proper amounts of vitamins and antioxidants is best accomplished with a balanced diet including 3 servings of vegetables and 2 servings of fruits. Regarding supplementation of specific vitamins: carotene cannot be recommended in view of the possible harm and lack of benefit in clinical studies. Vitamin A (retinol) and Vitamin D should be repleted if deficient by laboratory assay. Excesses should be avoided. Vitamin A supplements, particularly in pregnancy, should not exceed 10,000 IU daily or a supplement should not exceed 25,000 units weekly. Vitamin E (alpha-tocopherol) alone in doses of 400 units is of questionable value, and larger doses may cause intracranial hemorrhage or interact negatively with lipid-lowering drugs. Vitamin E should not be used in patients who have bleeding disorders or patients on anticoagulants or acetylsalicylic acid (ASA). Vitamin C (ascorbic acid) losses in urine may be excessive in diabetic patients and may require repletion to 200 mg in nonsmokers and 250 mg in smokers. Further studies are needed testing: (1) vitamin supplementation in subgroups of patients at high risk for specific complications using tissue-specific indicators of oxidative stress; (2) the role of oxidative stress in nephropathy, diabetic myocardiopathy, dermopathy, joint limitation syndromes, peripheral edema, metabolic bone disease, and pregnancy; (3) the impact of renal failure on oxidative stress; and (4) the effects of diabetes and dietary vitamins on the relative amounts of retinoids, carotenoids, and vitamin E in the chylomicron and lipoproteins, and how this affects assimilation, oxidation of lipids, and atherosclerotic plaque formation.
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PMID:Advances in diabetes for the millennium: vitamins and oxidant stress in diabetes and its complications. 1564 9

The daily requirement of a human person for vitamin C (ascorbic acid) has now been established at 100 mg. This value was already on the map when Arnold Durig put together the most important needs of nutritional ingredients. The modern value rests on the saturating level of ascorbate in leukocytes, which is in the millimolar range. The mechanism of accumulation of ascorbate in these cells rests on the uptake of oxidized dehydroascorbic acid. It is very efficient and avoids loss of vitamin which occurs in vitro when ascorbate is oxidized because of the great instability of the dehydro form. Therefore and increased requirement in case of infection is very unlikely from the biochemical point of view. However, low concentrations of ascorbate are found in patients suffering from arterial diseases or diseases accompanied by arterial damage such as diabetes mellitus. Ascorbate is known as a protection factor for the arterial endothel, but it is not clear by what mechanism this protection is brought about. Moreover, under clinical conditions very high concentrations are needed, which are achieved only by intravenous infusion, and the protection is only observed when the disease is manifest, not in healthy people. Therefore, also in this respect an increase in daily intake seems of no prophylactic value. Thus, by using high concentrations of ascorbate as an i.v. drug, effects of this substance frequently observed in vitro, could be used for therapy. This includes not only treatment of arterial diseases, but also relates to the cytotoxic effects of the vitamin against certain tumor cells and may assist conventional chemotherapy.
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PMID:Vitamin C: from popular food supplement to specific drug. 1580 91

Oxidative stress is currently hypothesized to be a mechanism underlying diabetes. The present study was designed to evaluate the effect of umbelliferone (UMB), a derivative of coumarin, on erythrocyte lipid peroxidation, antioxidants, and lipid profile in normal and streptozotocin (STZ) diabetic rats. Diabetes was induced in adult male albino rats of Wistar strain, weighing 180 to 200 g, by the administration of STZ (40 mg/kg/b-wt) intraperitonially. The normal and diabetic rats were treated with UMB in 10 percent dimethyl sulfoxide (DMSO) dissolved in water for 45 days. The diabetic rats had elevated levels of blood glucose and lipid peroxidation markers such as thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD), and lipid hydroperoxide (HP) and decreased levels of nonenzymatic antioxidants (Vitamin C and reduced glutathione [GSH]), elevated levels of vitamin E, and elevated levels of enzymatic antioxidants (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx]), elevated glucose-6-phosphate dehydrogenase activity, and altered lipid profile (cholesterol and phospholipids) in erythrocytes. These changes were reversed by treatment with UMB. Thus, our results indicate that the administration of UMB shows promising potential for the restoration of normal blood glucose levels, erythrocyte lipid peroxidation, antioxidants, and lipid profile in STZ-diabetic.
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PMID:Impact of umbelliferone on erythrocyte redox status in STZ-diabetic rats. 1646 11

L-Ascorbic acid interacts with vanadium(V) over the pH range of 0.4-7.0 to form three different coordination complexes. Both inner- and outer-sphere electron-transfer pathways are proposed to form vanadium(IV) complexes with L-ascorbate or dehydroascorbate, respectively. Effects of the pH on the coordination of L-ascorbic acid to the vanadium(V) center were observed and are presumably related to the speciation of the vanadium(V) ion. Three vanadium(IV) complexes were observed using ambient-temperature electron paramagnetic resonance spectroscopy. Two of these complexes are proposed to be vanadium(IV) L-ascorbate complexes, and one is consistent with a vanadium(IV) dehydroascorbic acid complex proposed earlier. These reduction reactions will occur under physiological conditions and could be important to the reduction of vanadium(V)-containing coordination complexes used as insulin-enhancing agents for treatment of diabetes.
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PMID:Reduction of vanadium(V) by L-ascorbic acid at low and neutral pH: kinetic, mechanistic, and spectroscopic characterization. 1647 58

There is evidence that oxidative stress might be implicated in promoting a state of systemic inflammation in diabetic patients. Understanding the role of reactive oxygen species in the inflammatory response in diabetes becomes essential in finding preventive treatments. Pioglitazone is a new oral antidiabetic agent with potent antioxidant and anti-inflammatory properties. The drug is a high affinity ligand of peroxisome proliferator-activated receptor gamma. This receptor seems to be involved in the control of inflammation by modulating the production of inflammatory mediators. In the present study, the changes in some markers of enhanced oxidative stress and in the level of pro-inflammatory interleukin-6 (IL-6) were examined in plasma of diabetic rabbits after 4 and 8 weeks of pioglitazone treatment. Ascorbic acid (AA) concentration and total antioxidant status (TAS) in plasma of diabetic animals were diminished and significantly elevated after pioglitazone treatment (p < 0.05). Protein carbonyl groups (PCG) content and IL-6 concentration were elevated in plasma of diabetic animals and significantly diminished after pioglitazone treatment. The results obtained in the present study confirm the relations of cytokine systems with oxidative stress in plasma of diabetic subjects. They also suggest the antioxidative and antinflammatory properties of pioglitazone.
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PMID:Interleukin-6 and oxidative stress in plasma of alloxan-induced diabetic rabbits after pioglitazone treatment. 1668 69

Impaired vascular reactivity is a hallmark of several cardiovascular diseases that include hypertension and diabetes. This study compared the changes in vascular reactivity in age-matched experimental hypertension and diabetes, and, subsequently, tested whether these changes could be affected directly by ascorbic acid (10 microM). Endothelium-derived nitric oxide (NO) modulation of ascorbic acid effects was also investigated. All the experiments were performed in the presence of a cyclooxygenase inhibitor, indomethacin (10 microM). Results showed that the endothelium-dependent and -independent relaxations induced by acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, were blunted to a similar extent in isolated aortic rings from age-matched spontaneously hypertensive (SHR) (R(max): ACh = 72.83+/-1.86%, SNP = 96.6+/-1.90%) and diabetic (Rmax: ACh = 64.09+/-5.14%, SNP = 95.84+/-1.41%) rats compared with aortic rings of normal rats (Rmax: ACh = 89%, SNP = 104.0+/-1.0%). The alpha1-receptor-mediated contractions induced by phenylephrine (PE) were augmented in diabetic (Cmax = 148.8+/-9.0%) rat aortic rings compared to both normal (Cmax = 127+/-6.9%) and SHR (Cmax = 118+/-4.5%) aortic rings. Ascorbic acid pretreatment was without any significant effects on the vascular responses to ACh, SNP and PE in aortic rings from normal rats. Ascorbic acid significantly improved ACh-induced relaxations in SHR (Rmax = 89.09+/-2.82%) aortic rings to a level similar to that observed in normal aortic rings, but this enhancement in ACh-induced relaxations was only partial in diabetic aortic rings. Ascorbic acid lacked any effects on SNP-induced relaxations in both SHR and diabetic aortic rings. Ascorbic acid markedly attenuated contractions induced by PE in aortic rings from both SHR (Cmax = 92.9+/-6.68%) and diabetic (Cmax = 116.9+/-9.4%) rats. Additionally, following inhibition of nitric oxide synthesis with l-NAME, ascorbic acid attenuated PE-induced contractions in all aortic ring types studied. These results suggest that (1) vascular hyper-responsiveness to alpha(1)-receptor agonists in diabetic arteries is independent of endothelial nitric oxide dysfunction; (2) ascorbic acid directly modulates contractile responses of hypertensive and diabetic rat aortas, likely through mechanisms in part independent of preservation of endothelium-derived nitric oxide.
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PMID:Effects of ascorbic acid on impaired vascular reactivity in aortas isolated from age-matched hypertensive and diabetic rats. 1680 25


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