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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Almost all diabetic complications are known to be associated with vascular dysfunctions of different tissues. Oxidative stress, on the other hand, has been implicated in the pathogenesis of diabetes mellitus. Therefore in the present study we have investigated the correlation between redox status and oxidative stress in the eyes, aorta and kidneys of streptozotocin (STZ)-induced diabetic rats. Glutathione (GSH), the primary endogenous antioxidant, and malondialdehyde (MDA), a marker of oxidative stress, were measured in these tissues of diabetic rats at different time points after STZ injection. Our results showed that GSH was reduced significantly in both the eyes and aorta of diabetic rats 8 weeks after STZ injection (43% and 66% of the control, respectively). Furthermore, the depletion of GSH occurred from the first week after STZ injection, and the level remained low as compared with the control rats (both week 1 and week 8: 43% and 66% of the control in the eyes and aorta, respectively). MDA was not increased until week 8 onwards after STZ-injection (177% and 93% of the control in the eyes and aorta, respectively). These changes, however, were not found in the kidneys, in which the GSH was slightly increased and MDA remained comparable to the control rats. These results indicate different tissues respond differently to high glucose conditions as redox changes and oxidative stress occurred only in the eyes and aorta but not in the kidneys of diabetic rats. In addition, the onset of oxidative stress is preceded by a depletion of GSH and probably an exhaustion of the antioxidant defense system. Furthermore, administration of Vitamin E was found to normalize MDA levels in the eyes and aorta but not in the kidneys of diabetic rats. In summary, our results suggest that the underlying mechanism in developing diabetic complications in the eyes and aorta involves the occurrence of oxidative stress, which may not be the case in diabetic kidneys. In addition, Vitamin E may prevent the development of diabetic complications in the eyes and aorta by reducing lipid peroxidation and oxidative damage in the cells.
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PMID:Redox changes precede the occurrence of oxidative stress in eyes and aorta, but not in kidneys of diabetic rats. 1296 80

Phosphodiesterase (PDE) inhibitors represent an important advance in the treatment of erectile dysfunction (ED). In spite of widespread use and generally good efficacy, as a class they remain ineffective in 15-57% of men. Specific cohorts of patients with severe vascular or neurogenic basis to their ED, such as diabetic men or those who have undergone radical pelvic surgery, demonstrate lower response rates with PDE inhibition treatment. We believe that circulating levels of nitric oxide (NO) may be enhanced through delivery of adequate concentrations of free oxygen radical scavenger molecules such as vitamin E. Higher levels of NO, theoretically, should produce increased penile blood flow with the potential for a synergistic effect when combined with a PDE5 inhibitor. With this hypothesis in mind, 20 adult male Sprague-Dawley streptozotocin-induced (60 mg/kg i.p.) diabetic rats were divided into four therapeutic groups (n=5). Group I--control animals received peanut oil, group II--vitamin E 20 IU/day, group III--sildenafil 5 mg/kg/day and group IV--vitamin E 20 IU/day plus sildenafil 5 mg/kg/day, by oral gavage daily for 3 weeks. Erectile function was assessed as a rise in intracavernous pressure following cavernous nerve electrostimulation. Penile tissue was harvested to determine the changes in tissue morphology including neuronal nitric oxide synthase, smooth muscle alpha-actin and endothelial cell integrity. PDE5 protein content and activity were measured. Significant increases in intracavernous pressure were measured in the animals receiving combined vitamin E plus sildenafil treatment. Immunohistochemical staining showed increases of neuronal nitric oxide synthase, endothelial cell and smooth muscle cell staining. Western blot analysis did not show significant differences of PDE5 protein between the groups. However, higher PDE5 activity was measured in the sildenafil group and lower activity of PDE5 was recorded in the cohort receiving vitamin E with sildenafil. Vitamin E enhanced the therapeutic effect of the PDE5 inhibitor in a meaningful way in this animal model of diabetes. This study indicates a potential means of salvaging erectile function among patients who are refractory to sildenafil.
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PMID:Effect of PDE5 inhibition combined with free oxygen radical scavenger therapy on erectile function in a diabetic animal model. 1456 36

We investigated a possible alteration in the ability of leukocytes to produce reactive oxygen species by stobadine, a pyridoindole antioxidant, in streptozotocin-diabetic rats. The production of free radicals from whole blood was assessed by luminol-enhanced chemiluminescence after stimulation by phorbol myristate acetate. The effects of vitamin E treatment were also evaluated and compared with the effects of combined treatment with stobadine. Diabetes was induced by streptozotocin (55 mg/kg i.p.). Some of diabetic rats and their age-matched controls were treated orally with a low dose of stobadine (24.7 mg/kg/day), vitamin E (400-500 IU/kg/day), or stobadine plus vitamin E for 10 weeks. Stobadine and vitamin E separately produced, to a similar degree, a reduction in diabetes-induced hyperglycemia. The phorbol myristate acetate stimulated chemiluminescence signal was markedly depressed in both moderate and severe diabetic rats. Stobadine treatment prevented this depression of the chemiluminescence response. Vitamin E treatment also eliminated the depression of the chemiluminescence signal in diabetic rats, and the combination with stobadine did not produce further improvement in leukocyte function. These results suggest that stobadine treatment alone is able to produce beneficial effects on leukocyte function and to maintain leukocyte free radical release during diabetes.
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PMID:Effect of stobadine on leukocyte free radical generation in streptozotocin-diabetic rats: comparison with vitamin E. 1464 50

Alongside increased proteolysis, the inability to repair damaged skeletal muscle is a characteristic feature of uncontrolled diabetes. This study evaluates the role of oxidative stress in muscle-specific gene regulatory regions and myosin chain synthesis in streptozotocin (STZ)-induced diabetic and ZDF rats. In the gastrocnemius muscle of diabetic rats, prooxidant compounds were seen to increase while antioxidant levels fell. Myogenic regulatory factors--Myo, myogenin, and Jun D--were also reduced, and muscle enhancer factor (MEF)-1 DNA binding activity was impaired. Moreover, synthesis of muscle creatine kinase and both heavy and light chains of myosin were impaired, suggesting that oxidative stress triggers the cascade of events that leads to impaired muscle repair. Dehydroepiandrosterone has been reported to possess antioxidant properties. When it was administered to diabetic rats, in addition to an improved oxidative imbalance there was a recovery of myogenic factors, MEF-1 DNA binding activity, synthesis of muscle creatine kinase, and myosin light and heavy chains. Vitamin E administration to STZ-induced diabetic rats reverses oxidative imbalance and improves muscle gene transcription, reinforcing the suggestion that oxidative stress may play a role in diabetes-related impaired muscle repair.
Diabetes 2004 Apr
PMID:Oxidative stress impairs skeletal muscle repair in diabetic rats. 1504 25

Atherosclerosis and its complications such as coronary heart disease, myocardial infarction and stroke are the leading causes of death in the developed world. High blood pressure, diabetes, smoking and a diet high in cholesterol and lipids clearly increase the likelihood of premature atherosclerosis, albeit other factors, such as the individual genetic makeup, may play an additional role. Several epidemiological studies and intervention trials have been performed with vitamin E, and some of them showed that it prevents atherosclerosis. For a long time, vitamin E was assumed to act by decreasing the oxidation of LDL, a key step in atherosclerosis initiation. However, at the cellular level, vitamin E acts by inhibition of smooth muscle cell proliferation, platelet aggregation, monocyte adhesion, oxLDL uptake and cytokine production, all reactions implied in the progression of atherosclerosis. Recent research revealed that these effects are not the result of the antioxidant activity of vitamin E, but rather of precise molecular actions of this compound. It is assumed that specific interactions of vitamin E with enzymes and proteins are at the basis of its non-antioxidant effects. Vitamin E influences the activity of several enzymes (e.g. PKC, PP2A, COX-2, 5-lipooxygenase, nitric oxide synthase, NADPH-oxidase, superoxide dismutase, phopholipase A2) and modulates the expression of genes that are involved in atherosclerosis (e.g. scavenger receptors, integrins, selectins, cytokines, cyclins). These interactions promise to reveal the biological properties of vitamin E and allow designing better strategies for the protection against atherosclerosis progression.
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PMID:Anti-atherosclerotic effects of vitamin E--myth or reality? 1509 Feb 61

Oxidative stress is involved in several pathological conditions, including diabetes. Reactive oxygen species (ROS) have been demonstrated to act as second messengers for several hormones and cytokines, including insulin (INS). The effect of Cu(2+)-oxidized LDL (CuLDL) on INS-induced generation of ROS and on INS signaling was investigated on cultured human fibroblasts. Intracellular ROS generation was observed either in CuLDL- or in INS-treated cells. Moreover, CuLDL and INS had an additive effect on ROS formation in human fibroblasts. CuLDL by itself increased the phosphorylation of ERK without affecting the PKB/Akt phosphorylation. CuLDL also stimulated the DNA binding activities of the transcription factors AP1 and NFkappaB. However, CuLDL dose-dependently prevented the INS-signaling pathway, by inhibiting the INS-induced phosphorylation of the signaling kinases ERK and PKB/Akt and the INS-induced activation of the transcription factors AP1 and NFkappaB. Finally, the lipophilic antioxidant Vitamin E (Vit E) partially restored all the studied signaling events initiated by INS and impaired after pretreatment with CuLDL. These studies demonstrate that the oxidative stress generated by CuLDL has a negative effect on the INS-signaling pathway, independently of the INS-induced generation of ROS. Thus, oxidized LDL might be involved not only in atherosclerosis, as it is commonly admitted, but also in the INS-resistance observed in type 2 diabetes mellitus.
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PMID:Inhibition of insulin signaling by oxidized low density lipoprotein. Protective effect of the antioxidant Vitamin E. 1518 43

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

This experimental study was designed to investigate the effects of vitamin E supplementation, especially on lipid peroxidation and antioxidant status elements 3/4 namely, glutathione (GSH), CuZn superoxide dismutase (CuZn SOD), and glutathione peroxidase (GSH Px), both in blood and liver tissues of streptozotocin (STZ) diabetic rats. The extent to which blood can be used to reflect the oxidative stress of the liver is also investigated. In diabetic rats, plasma lipid peroxide values were not significantly different,from control,whereas erythrocyte CuZn SOD (p < 0.01), GSH Px (p < 0.001) activities and plasma vitamin E levels (p < 0.001), were significantly more elevated than controls. Vitamin E supplementation caused significant decreases of erythrocyte GSH level (p < 0.01) in control rats and of erythrocyte GSH Px activity (p < 0.05) in diabetic rats. Liver findings revealed significantly higher lipid peroxide (p < 0.001) and vitamin E (p < 0.01) levels and lower GSH (p < 0.001), CuZn SOD (p < 0.001) and GSH Px (p < 0.01) levels in diabetic rats. A decreased hepatic lipid peroxide level (p < 0.01) and increased vitamin E/lipid peroxide ratio (p < 0.001) were observed in vitamin E supplemented, diabetic rats. A vitamin E supplementation level which did not cause any increase in the concentration of the vitamin in the liver or blood, was sufficient to lower lipid peroxidation in the liver. Vitamin E/lipid peroxide ratio is suggested as an appropriate index to evaluate the efficiency of vitamin E activity,independent of tissue lipid values. Further, the antioxidant components GSH, GSH Px and CuZn SOD and the relationships among them, were affected differently in the liver and blood by diabetes or vitamin E supplementation.
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PMID:Effects of vitamin E supplementation on oxidative stress in streptozotocin induced diabetic rats: investigation of liver and plasma. 1534 13

Long-standing diabetes can result in the development of cardiomyopathy, which can be accompanied by myocardial fibrosis. Although exposure of cultured kidney and skin fibroblasts to high glucose (HG) concentration is known to increase collagen synthesis, little is known about cardiac fibroblasts (CFs). Therefore, we determined the influence of HG conditions on CF functions and the effects of losartan and vitamin E in these responses. We cultured rat CFs in either normal glucose (NG; 5.5 mM) or HG (25 mM) media and assessed changes in protein and collagen synthesis, matrix metalloproteinase (MMP) activity, and levels of mRNA for ANG II type 1 (AT(1)) receptors. Results indicate that HG-level CFs synthesized more protein and collagen, and these effects were not due to changes in osmotic pressure. The addition of ANG II stimulated protein and collagen synthesis in NG-concentration but not HG-concentration CFs. Interestingly, losartan pretreatment blocked the HG- or ANG II-induced increases in both protein and collagen synthesis. HG or ANG II decreased total MMP activity. Decreases in MMP activity were blocked by losartan. AT(1) mRNA levels were upregulated with HG concentration. Vitamin E pretreatment blocked the effects of HG on total protein synthesis and stimulated MMP activity. Results suggest that HG levels may promote fibrosis by increasing CF protein and collagen synthesis and decreasing MMP activity. HG levels may cause these effects via the upregulation of AT(1) receptors, which can be blocked by losartan. However, vitamin E can alter HG concentration-induced changes in CF functions independently of AT(1) mRNA levels.
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PMID:Profibrotic influence of high glucose concentration on cardiac fibroblast functions: effects of losartan and vitamin E. 1534 78

Defective intracellular antioxidant enzyme production (IAP) has been demonstrated in adults with diabetic nephropathy. To evaluate the effects on IAP of vitamin E administration in adolescents with type 1 diabetes and early signs of microangiopathy, 12 adolescents (aged 11-21 y; diabetes duration 10-18) were studied. Eight had retinopathy [background (four), preproliferative (three), or proliferative (one)], four had persistent microalbuminuria, and seven had both. Skin fibroblasts were obtained by biopsies and cultured in Dulbecco's modified Eagle's medium. CuZn superoxide dismutase (SOD), MnSOD, catalase (CAT), and glutathione-peroxidase (GPX) activity and mRNA expression were measured before and after 3 mo of synthetic vitamin E supplementation (600 mg twice daily); on both occasions, IAP was evaluated at different ex vivo glucose concentrations (5 and 22 mM). Ten adolescents with type 1 diabetes (aged 12-20 y) without angiopathy and eight healthy volunteers (aged 15-22 y) participated as control subjects. Vitamin E serum levels were measured throughout the study. In normal glucose concentrations, CuZnSOD, MnSOD, CAT, and GPX activity and mRNA expression were not different among the groups. In high glucose, CuZnSOD activity and mRNA increased similarly in all groups [angiopathics: 0.96 +/- 0.30 U/mg protein; 9.9 +/- 3.2 mRNA/glyceraldehyde-3-phosphate dehydrogenase). CAT and GPX activity and mRNA did not increase in high glucose only in adolescents with angiopathy (0.35 +/- 0.09; 4.2 +/- 0.1 and 0.52 +/- 0.14; 2.4 +/- 0.9, respectively). MnSOD did not change in any group. Vitamin E supplementation had no effect on any enzymatic activity and mRNA in both normal and hyperglycemic conditions. Adolescents with early signs of diabetic angiopathy have defective IAP and activity, which are not modified by vitamin E.
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PMID:Effects of vitamin E supplementation on intracellular antioxidant enzyme production in adolescents with type 1 diabetes and early microangiopathy. 1534 73


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