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

Erectile dysfunction is a common complication of diabetes. Diabetes can cause neuropathy or damage to nerves throughout your body, including the penis. Damaged nerves can't communicate properly. So even though you might be emotionally stimulated to have intercourse, nerve damage means that information isn't relayed to the penis, and it doesn't respond. In addition, poor blood sugar control can inhibit nitric oxide production. Lack of nitric oxide can prevent the pressure of blood in the corpora cavernosa from rising enough to close off penile veins, allowing blood to flow out of the penis instead of remaining trapped for an erection. This prospective, randomized, double-blind, placebo-controlled study included 176 patients with type 2 diabetes. The daily 4 g dose of inositol plus 400 microg of folic acid or placebo was divided and given in three doses. The present study demonstrates that Myoinositol/folic acid combination, deserves consideration as therapeutic agent for preventing and treating erectile dysfunction in diabetic men, probably by virtue of both their chronic metabolic, acute ROS scavenging, and NO protective beneficial effects.
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PMID:Myoinositol/folic acid combination for the treatment of erectile dysfunction in type 2 diabetes men: a double-blind, randomized, placebo-controlled study. 1712 17

Excessive formation of oxygen radicals is a well-established mediator of hyperglycemic damage in diabetes to a wide range of tissues, such as neurons, retinal cells, and vascular endothelium. Increased oxygen radical formation is generally considered a toxic side effect of excessive rates of mitochondrial oxidative metabolism and electron transport in high glucose-exposed cells. Along the same line, metabolic oxidative stress is currently also regarded as crucial mediator of beta cell dysfunction and apoptosis under hyperglycemic conditions. Here the authors argue that a healthy beta cell is well equipped to deal adequately with elevated glucose metabolic rates, and demonstrate that decreased glucose catabolism leads to ROS production and apoptosis. They therefore propose that adverse metabolic conditions in poorly controlled diabetes (hyperglycemia and/or dyslipidemia) or genetic defects could decrease the viability of beta cells by interfering with normal glucose sensing and metabolism, rather than by overactivating it. This view is supported by the fragmentary data currently available on the pathways for hypergycemic and hypoglycemic beta cell death.
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PMID:Glycemic control of apoptosis in the pancreatic beta cell: danger of extremes? 1718 75

Experimental induction of diabetes mellitus in animal models using chemical diabetogens is demonstrated to impair testicular function progressively leading to decreased fertility. Although, both steroidogenic and spermatogenic dysfunctions have been reported, the role of oxidative stress mechanism/s has been less understood. We have investigated the induction of oxidative damage during early diabetic phase in testis and epididymal sperm (ES) in mice administered an acute dose of streptozotocin (STZ). Our results show enhanced lipid peroxidation in testis (cytosol and mitochondria) and ES and increased ROS production as early as 5 days. Further, significant perturbations in the activities of antioxidant enzymes in testis/ES and enhanced protein carbonyl content were suggestive of increased oxidative stress during early diabetic phase. STZ-induced oxidative damage in both compartments was amenable for attenuation by treatment with oral supplements of either ascorbic acid (10mg/(kg(bw)day)) or taurine (1g/(kg(bw)day)). Furthermore, the oxidative impairments in testis/ES were persistent during the progressive phase (as measured at 2 and 4 weeks of sampling) and were associated with significant increase DNA damage (testis) and higher incidence of abnormal sperms. Interestingly, mating of STZ treated males sequentially for a period of 5 weeks with virgin untreated females resulted in a significant increase in the male-mediated dominant lethal-type mutations during the first 3 weeks, indicating a stage-specific genotoxic effect on post-meiotic germ cells. Based on the occurrence of oxidative impairments in STZ-treated mice both during both early and progressive phase, it is hypothesized that oxidative stress mechanisms may be wholly or in part contribute towards the development of testicular dysfunction and degeneration under situations of experimentally induced diabetes in animal models.
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PMID:Early oxidative stress in testis and epididymal sperm in streptozotocin-induced diabetic mice: its progression and genotoxic consequences. 1736 Jan 55

Glucose-induced insulin secretion from beta-cells is often impaired in diabetic condition and by exposure to diabetogenic pharmacological agents. In pancreatic beta-cells, intracellular glucose metabolism regulates exocytosis of insulin granules, according to metabolism-secretion coupling in which glucose-induced mitochondrial ATP production plays an essential role. Impaired glucose-induced insulin secretion often results from impaired glucose-induced ATP elevation in beta-cells. Mitochondrial ATP production is driven by the proton-motive force including mitochondrial membrane potential (DeltaPsi(m)) generated by the electron transport chain. These electrons are derived from reducing equivalents, generated in the Krebs cycle and transferred from cytosol by the shuttles. Here, roles of the determinants of mitochondrial ATP production in impaired glucose-induced insulin secretion are discussed. Cytosolic alkalization, H(+) leak in the inner membrane by uncoupler (e.g. free fatty acid exposure), decrease in the supply of electron donors including NADH and FADH(2) to the respiratory chain, and endogenous mitochondrial ROS (e.g. Na(+)/K(+)-ATPase inhibition) all reduce hyperpolarlization of DeltaPsi(m) and ATP production, causing decresed glucose-induced insulin release. The decrease in the supply of NADH and FADH(2) to the respiratory chain derives from impairments in glucose metabolism including glycolysis (e.g. MODY2 and exposure to NO) and the shuttles (e.g. diabetic state and exposure to ketone body).
Diabetes Res Clin Pract 2007 Sep
PMID:Impaired metabolism-secretion coupling in pancreatic beta-cells: role of determinants of mitochondrial ATP production. 1744 30

Vascular diseases are important clinical complications of diabetes. Advanced glycation end-products (AGE) are mediators of vascular dysfunction, but their effects on vascular smooth muscle cell (VSMC) ROS production are unclear. We studied the source and downstream targets of AGE-mediated ROS and reactive nitrogen species production in these cells. Significant increases in superoxide production in AGE-treated VSMC were measured using lucigenin (7650+/-433 vs 4485+/-424 LU/10(6) cells, p<0.001) or coelenterazine (277,907+/-71,295 vs 120,456+/-4140 LU/10(6) cells, p<0.05) and confirmed by ESR spectroscopy. These signals were blocked by the flavin-containing oxidase inhibitor diphenylene iodonium (DPI). AGE-stimulated NF-kappaB activity was abolished by DPI and the superoxide scavenger MnTBAP. AGE differentially regulated VSMC NADPH oxidase catalytic subunits, stimulating the transcription of Nox1 (201+/-12.7%, p<0.0001), while having no effect on Nox4. AGE also increased 3-nitrotyrosine formation, which was inhibited by MnTBAP, DPI, or the NOS inhibitor L-NAME. Regarding the source of NO, AGE stimulated inducible nitric oxide synthase mRNA (1 vs 9.7+/-3.0, p=0.046), which was abolished by a NF-kappaB inhibitor, SOD, catalase, or siRNA against Nox1. This study establishes that AGE activate iNOS in VSMC through a ROS-sensitive, NF-kappaB-dependent mechanism involving ROS generation by a Nox1-based oxidase.
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PMID:Nox1-based NADPH oxidase-derived superoxide is required for VSMC activation by advanced glycation end-products. 1746 35

We aimed to investigate the extent to which maternal diabetes with or without folic acid (FA) supplementation affects mRNA levels and protein distribution of ROS scavenging enzymes, vascular endothelial growth factor-A (Vegf-A), folate binding protein-1 (Folbp-1), and apoptosis-associated proteins in the yolk sacs of rat embryos on gestational days 10 and 11. Commencing at conception and throughout pregnancy, half of the streptozotocin-diabetic and half of the control rats received daily FA injections. Maternal diabetes impaired vascular morphology and decreased CuZnSOD and GPX-1 gene expression in yolk sacs. Maternal diabetes also increased the levels of CuZnSOD protein, increased the Bax/Bcl-2 protein ratio and decreased Vegf-A protein distribution. FA treatment normalized vascular morphology, decreased mRNA levels of all three SOD isoforms and increased Vegf-A mRNA levels, rectified CuZnSOD protein distribution and Bax/Bcl-2 ratio. A teratogenic diabetic environment produces a state of vasculopathy, oxidative stress, and mild apoptosis in the yolk sac. FA administration normalizes vascular morphology, diminishes apoptotic rate, and increases Vegf-A gene expression and protein distribution in the yolk sac of diabetic rats.
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PMID:Folic acid supplementation affects ROS scavenging enzymes, enhances Vegf-A, and diminishes apoptotic state in yolk sacs of embryos of diabetic rats. 1748 24

Calcium ion is an essential structural component of the skeleton. There is growing evidence for the importance of nutrition in the maintenance of bones and joints health. Nutritional imbalance combined with endocrine abnormalities may be involved in osteoporosis. For example, essential fatty acids and their metabolites were reported to have beneficial action in osteoporosis. The mechanism by which fatty acids prevent osteoporosis may involve inhibition of pro-inflammatory cytokines, which are known to have a major role in osteoporosis through induction of oxidative stress which had adverse effects on the skeleton. Other risk factors for osteoporosis, such as smoking, hypertension and diabetes mellitus are also associated with increased oxidative stress and free radicals levels. When bone fracture occurs, a remarkable yield of free radicals is generated by the damaged tissues. However, controlled production of free radicals by normally functioning osteoclasts could accelerate destruction of calcified tissues and assist bone remodeling. Enhanced osteoclastic activity observed in bone disorders may have been responsible for increased production of reactive oxygen species [ROS] in the form of superoxide, which is evident by increased levels of serum malondialdehyde [MDA] levels. One of the most damaging effects of ROS is lipid peroxidation, the end product of which is MDA which also served as a measure of osteoclastic activity. Inhibition of the antioxidant enzymes activities, such as superoxide dismutase and glutathione peroxidase, was found to increase superoxide production by the osteoclasts which represented by increased levels of MDA. Therefore, oxidative stress is an important mediator of bone loss since deficiency of antioxidant vitamins has been found to be more common in the elderly osteoporotic patients. It is concluded from this review that increased free radical production overwhelms the natural antioxidants defense mechanisms, subjecting individuals to hyperoxidant stress and thus leading to osteoporosis. In addition, administration of antioxidants might protect bones from osteoporosis and also might help in the acceleration of healing of fractured bones.
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PMID:Calcium metabolism and oxidative stress in bone fractures: role of antioxidants. 1758 23

Black foot disease (BFD) is a peripheral arterial occlusive disease found among the inhabitants of the southwest coast of Taiwan. Moreover, within the BFD-endemic areas, diabetes mellitus occur at significantly higher rates than in other areas of Taiwan. A high concentration of humic acid (HA), and arsenic (As) are present in the artesian well water from BFD-endemic area. The aim of this paper is to study the diabetogenic effect of the combination of HA and AS. Treatment of HIT-T15 cells with HA, As, or both of them resulted loss of cell viability, apoptosis, depletion of ATP, increment of oxidative stress, activation of caspase 3, and dysfunction of insulin secretion. In addition, the plasma insulin of ICR mice, which were exposed to HA and As in drinking water for 12 weeks, was decreased in the 5, 7, and 12 weeks, and increased at early stage of exposure (3 weeks). The results reported herein reveal that HA and As exert HIT-T15 cell dysfunction and inhibited insulin secretive effects. In addition, the sub-acute peri-pancreatitis and islet damage caused by the infiltration of inflammatory cells after exposure of HA and As in drinking water for 5 weeks. Our study has important implications in the diabetogenic effect of the HA and AS which may be mediated by ROS and further information of the toxicity mechanisms will provide under our progressive studies.
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PMID:The diabetogenic effects of the combination of humic acid and arsenic: in vitro and in vivo studies. 1762 97

The therapeutic properties of honey, once considered a form of folk or preventive medicine, are acquiring importance for the treatment of acute and chronic free radical-mediated diseases (atherosclerosis, diabetes and cancer). The aim of this work was to study the protective activity of a honey of multifloral origin, standardized for total antioxidant power and analytically profiled (HPLC-MS) in antioxidants, in a cultured endothelial cell line (EA.hy926) subjected to oxidative stress. Cumene hydroperoxide (CuOOH) was used as free radical promoter. Native honey (1% w/v pH 7.4, 10(6) cells) showed strong quenching activity against lipophilic cumoxyl and cumoperoxyl radicals, with significant suppression/prevention of cell damage, complete inhibition of cell membrane oxidation, of intracellular ROS production and recovery of intracellular GSH. Experiments with endothelial cells fortified with the isolated fraction from native honey enriched in antioxidants, exposed to peroxyl radicals from 1,1-diphenyl-2-picrylhydrazyl (AAPH, 10 mM) and to hydrogen peroxide (H2O2, 50-100 microM), indicated that phenolic acids and flavonoids were the main causes of the protective effect. These results provide unequivocal evidence that, through the synergistic action of its antioxidants, honey by reducing and removing ROS, may lower the risks and effects of acute and chronic free radical induced pathologies in vivo.
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PMID:Antioxidant and radical scavenging activity of honey in endothelial cell cultures (EA.hy926). 1782 75

The present study was designed to investigate the relationship between the serum levels of oxidant-antioxidant system (malondialdehyde (MDA) level, Paraoxonase (PON1) activity, nitric oxide (NO) level and superoxide dismutase (SOD) activity) and thyroid hormone status in hypothyroidism pre and posttreatment. The study group comprised 33 patients with primary hypothyroidism. 18 of these patients were reevaluated after euthyroid state i.e. at least 6 months of thyroxine replacement. The patients were compared with 26 normal healthy controls. Serum MDA level, PON1 activity, NO level and SOD activity were measured according to an enzymatic spectrophotometric method. MDA levels were found higher in patients with hypothyroidism before the treatment than the controls. MDA levels were also found to be decreased after the treatment in patients with hypothyroidism. However MDA were found still higher than the controls after the treatment. PON1 activity was found to be lower in patients pretreatment when compared to posttreatment hypothyroidism and controls. Posttreatment of hypothyroidism mean PON1 activity significantly increased compared to pretreatment level but it was still significantly lower than control level. NO level was higher in pretreatment hypothyroidism when compared to controls. SOD activity was not found different in patients before treatment when compared to controls. SOD activity was significantly higher in after treatment when compared to both pretreatment and control levels. In conclusion, increased ROS levels in hypothyroidism may result in a pro-oxidation environment, which in turn could result in decreased antioxidant PON1 activity, increased MDA and NO levels. As a result, lipid peroxidation may have a role in the pathogenesis of the atherosclerosis in hypothyroidism.
Exp Clin Endocrinol Diabetes 2007 Sep
PMID:Oxidative stress and enzymatic antioxidant status in patients with hypothyroidism before and after treatment. 1785 36


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