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

Oxidative stress plays an important role in tissue damage caused by hypoglycemia and diabetes, which may be the result of deterioration in glucose homeostasis caused by these metabolic disorders. The present study examined the effects of insulin-induced hypoglycemia and streptozotocin induced diabetes on mitochondrial lipid peroxidation and antioxidant enzymes from different brain regions, namely, cerebral hemispheres, cerebellum, brain stem and diencephalon. In situ localization of DNA single strand breaks (SSBs) were also studied by DNA polymerase-I mediated biotin dATP labeled nick translation method after inducing hypoglycemia and diabetes. Significant decrease in mitochondrial catalase, manganese superoxide-dismutase (Mn-SOD) and reduced glutathione (GSH) content and increase in the lipid peroxidation (LPx) and glutathione peroxidase (GPx) activity was observed under these metabolic stress conditions with more pronounced effects in hypoglycemic group. We conclude that during severe energy deprivation following hypoglycemia and diabetes, mitochondrial free radicals scavenger system is down regulated, which leads to reactive oxygen species (ROS) generation. High levels of ROS in turn activate the processes leading to DNA damage. DNA SSBs, which indicates nuclear disintegration is an important feature of neuronal cell death.
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PMID:Impact of hypoglycemia and diabetes on CNS: correlation of mitochondrial oxidative stress with DNA damage. 1522 97

The process of human islet isolation triggers a cascade of stressful events in the islets of Langerhans involving activation of apoptosis and necrosis and the production of proinflammatory molecules that negatively influence islet yield and function and may produce detrimental effects after islet transplantation. In this study, we showed that activation of nuclear factor-kappaB (NF-kappaB) and poly(ADP-ribose) polymerase (PARP), two of the major pathways responsible for cellular responses to stress, already occurs in pancreatic cells during the isolation procedure. NF-kappaB-dependent reactions, such as production and release of interleukin-6 and -8 and macrophage chemoattractant protein 1, were observed days after the isolation procedure in isolated purified islets. Under culture conditions specially designed to mimic isolation stress, islet proinflammatory responses were even more pronounced and correlated with higher islet cell loss and impaired secretory function. Here we present novel evidence that early interventions aimed at reducing oxidative stress of pancreatic cells and islets through the use of the catalytic antioxidant probe AEOL10150 (manganese [III] 5,10,15,20-tetrakis [1,3,-diethyl-2imidazoyl] manganese-porphyrin pentachloride [TDE-2,5-IP]) effectively reduces NF-kappaB binding to DNA, the release of cytokines and chemokines, and PARP activation in islet cells, resulting in higher survival and better insulin release. These findings support the concept that the isolation process predisposes islets to subsequent damage and functional impairment. Blocking oxidative stress can be beneficial in reducing islet vulnerability and can potentially have a significant impact on transplantation outcome.
Diabetes 2004 Oct
PMID:Response of human islets to isolation stress and the effect of antioxidant treatment. 1544 84

Reactive oxygen species, such as superoxide, and nitrogen oxides, such as peroxynitrite, are thought to contribute to beta-cell destruction during the disease process that leads to type 1 diabetes. EUK-8 is a member of a new class of synthetic salen-manganese compounds with low toxicity that possess catalytic superoxide dismutase, peroxidase, and catalase activity that can inactivate superoxide and nitrogen oxides (e.g., peroxynitrite and nitrogen dioxide). We observed that EUK-8 administration inhibited the adoptive transfer of type 1 diabetes to NOD mice. In addition, administration of EUK-8 to NOD mice with established autoimmunity completely prevented the development of type 1 diabetes for up to 1 year in age, even though the treatment was discontinued after 35 weeks of age. EUK-8 treatment also prolonged the survival of islet allografts in newly diabetic NOD mice. Thus, reactive oxygen and nitrogen species contribute to the pathoetiology of both spontaneous type 1 diabetes and allograft rejection. In cultures of NIT-1 cells, EUK-8 inhibited cytotoxicity caused by superoxide as well as nitric oxide. Collectively, our findings implicate a greater role for nitrogen oxides (other than peroxynitrite) in beta-cell damage. Antioxidants designed to prevent the formation of both cytotoxic reactive oxygen and nitrogen species may effectively protect beta-cells from spontaneous autoimmunity and alloresponses.
Diabetes 2004 Oct
PMID:A salen-manganese catalytic free radical scavenger inhibits type 1 diabetes and islet allograft rejection. 1544 86

Enhanced oxidative stress due to hyperglycemia has been implicated in diabetic complications and is considered a major cause of cell and tissue damage. The aim of the present study was to investigate whether synthetic manganese porphyrin, Mn(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin (MnTM-2-PyP5+) can ameliorate diabetes-induced oxidative stress and affect life span of diabetic rats. Diabetes was induced by a single (60 mg/kg) intraperitoneal injection of streptozotocin in male Wistar rats. Oxidative stress was monitored by measuring malondialdehyde levels (MDA) in blood plasma and erythrocytes using HPLC. The antioxidant status was assessed by measuring the total radical-trapping potential (TRAP) of blood plasma. Life span of the animals was used as an indication of the overall effect of MnTM-2-PyP5+. MnTM-2-PyP5+ was administered subcutaneously at 1 mg/kg for the duration of the experiment, five times/week followed by one week of rest. Diabetes increased plasma and erythrocyte levels of MDA and decreased TRAP. MnTM-2-PyP5+ had no effect on blood glucose and glycosylated hemoglobin, but significantly increased TRAP and lowered MDA. This Mn porphyrin decreased mortality and markedly extended the life span of the diabetic animals. MnTM-2-PyP5+ suppressed diabetes-induced oxidative stress, which presumably accounts for its beneficial effect on the life span of the diabetic rats. The results indicate that Mn(III) N-alkylpyridylporphyrins can be used as potent therapeutic agents in diabetes.
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PMID:A manganese porphyrin suppresses oxidative stress and extends the life span of streptozotocin-diabetic rats. 1587 15

We have shown that short-term exposure of rat small coronary arteries (RSCAs) to high glucose enhances superoxide (O2-*) formation and impairs cAMP-mediated dilation by reducing voltage-gated K+ (Kv) channel function. However, it is not clear whether the impairment also occurs in diabetes mellitus (DM), where alternate mechanisms could mask or aggravate vasodilator dysfunction. RSCAs were isolated from control and streptozotocin-induced diabetic rats. Reduced constriction to 4-aminopyridine (4-AP) was observed in RSCAs from DM rats, indicating Kv channel impairment. Forskolin increased 4-AP-inhibitable K+ channel open-state probability and whole cell K+ current density in coronary myocytes from non-DM rats but had little effect on K+ current density in cells from DM rats. Diminished dilation to 8-bromo-cAMP, forskolin, or isoproterenol was observed in DM RSCAs. The attenuated dilation to forskolin or isoproterenol in DM RSCAs was partially restored by application of the superoxide dismutase mimetic manganese[III] tetrakis (4-benzoic acid) porphyrin. Histofluorescence studies using hydroethidine revealed a blockage of O2-* generation by the NADPH oxidase inhibitor apocynin in DM RSCAs. Sepiapterin, a precursor of tetrahydrobiopterin, had little effect on hyperglycemia-induced O2-* formation. Consistent with the findings from the concurrent fluorescence study, apocynin also partially restored the reduced dilator response to forskolin in DM RSCAs. Forskolin-induced cAMP production was unaltered in DM. We conclude that in diabetes, enhanced O2-* formation by activation of NADPH oxidase impairs cAMP-medicated dilation in RSCAs by inhibiting Kv channel activity.
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PMID:Enhanced oxidative stress impairs cAMP-mediated dilation by reducing Kv channel function in small coronary arteries of diabetic rats. 1593 95

The role of some inorganic elements like vanadium, zinc, sodium, potassium, calcium, copper, manganese, and traces of chromium in the improvement of impaired glucose tolerance and their indirect role in the management of diabetes mellitus are being increasingly recognized. In traditional methods, medicinal plants are being used, which contain both organic and inorganic constituents. In the present study, an attempt has been made to analyze the inorganic elements present in Aloe vera leaf gel and their role on diabetes-related biochemical alterations in experimental rats. Special emphasis was given to the inorganic parts by carefully preparing ash of the leaf gel. The results clearly indicate the presence of several hypoglycemic-activity-possessing elements in the gel. The ash treatment also resulted in hypoglycemic action. In conclusion, the presence of various inorganic trace elements in the gel might account for the hypoglycemic nature of the plant.
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PMID:Mineral contents of aloe vera leaf gel and their role on streptozotocin-induced diabetic rats. 1632 71

Seven kinds of Chinese traditional medicines, including laoniankechuan tablet, fufangbanxia tablet, weitongning tablet, quanshen tablet, shengshijiangtang capsule, xiasangju particle, and American yangshen tablet, were digested with HNO3-HClO4 mixed acid. The fourteen trace elements, including calcium, magnesium, iron, zinc, potassium, sodium, manganese, copper, chromium, cobalt, strontium, nickel, cadmium and lead in the drugs were determined by atomic absorption spectrometry. The effects of the type of mixed acid, the ratio of HNO3 to HClO4 in mixed acid, the volume of digesting solution, and the digesting time were also investigated in detail. The results obtained show that the concentrations of Ca, Mg, Fe, K and Na in seven kinds of Chinese traditional medicines are higher than those of other elements. Moreover, shengshijiangtang capsule for the treatment of diabetes contains plenty of Mn, and weitongning tablet for the treatment of stomach disease contains plenty of Sr, Mn and Cu.
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PMID:[Determination of fourteen trace elements in chinese traditional medicines by atomic absorption spectrometry]. 1637 4

The increasing incidence of diabetes and the need to further understand its cellular basis has resulted in the development of new diagnostic and therapeutic techniques. Nonetheless, the quest to noninvasively ascertain beta-cell mass and function has not been achieved. Manganese (Mn)-enhanced MRI is presented here as a tool to image beta-cell functionality in cell culture and isolated islets. Similar to calcium, extracellular Mn was taken up by glucose-activated beta-cells resulting in 200% increase in MRI contrast enhancement, versus nonactivated cells. Similarly, glucose-activated islets showed an increase in MRI contrast up to 45%. Although glucose-stimulated Ca influx was depressed in the presence of 100 microM Mn, no significant effect was seen at lower Mn concentrations. Moreover, islets exposed to Mn showed normal glucose sensitivity and insulin secretion. These results demonstrate a link between image contrast enhancement and beta-cell activation in vitro, and provide the basis for future noninvasive in vivo imaging of islet functionality and beta-cell mass.
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PMID:Functional MR microimaging of pancreatic beta-cell activation. 1671 54

Decreased glucose tolerance is a first sign of diabetes mellitus and therefore rigorous control must be taken in carbohydrate and lipid metabolisms. Herbal remedies (lyophilized extracts of Myrtilli folium and Phaseoli fructus sine seminibus (L1), Myrtilli folium, Phaseoli fructus sine seminibus, and Salviae folium (L2) are traditionally used in mid-European folk medicine and in common adjuvant therapy for the prevention of complications in type 2 diabetes. Significant iron (355.7 +/- 13.8 mg/kg) and zinc (84.73 +/- 1.83 mg/kg) concentration was found in L1 and chromium (3.82 +/- 2.71 mg/kg) in L2. Ion concentrations in teas made from L1 and L2 are relatively low because the quantities of metal ions in teas do not cover the daily need, although the teas are good sources for some elements. According to the Recommended Daily Allowances, the tea of L1 is a good source for iron and manganese, whereas for chromium, the tea of L2 is better. For evaluating the element bioavailability, an in vitro dialysis system was applied to determine the element transfer from tea of the lyophilized sample to the plasma (buffer pH=7.4). Measurements showed that the elements transferred between 6.90% (iron from tea of L2) and 90.05% (chromium from tea of L2) through the membrane from teas to the plasma. Metal ions in teas of herbal remedies might contribute to the favorable therapeutic effect of preventing complications, because they might transfer through the membranes in relatively high percentages.
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PMID:In vitro study of elements in herbal remedies. 1720 97

The Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin, MnIIITE-2-PyP5+ (AEOL-10113) has proven effective in treating oxidative stress-induced conditions including cancer, radiation damage, diabetes, and central nervous system trauma. The ortho cationic pyridyl nitrogens of MnTE-2-PyP5+ are essential for its high antioxidant potency. The exceptional ability of MnIIITE-2-PyP5+ to dismute O2.- parallels its ability to reduce ONOO- and CO3-. Decreasing levels of these species are considered its predominant mode of action, which may also involve redox regulation of signaling pathways. Recently, Ferrer-Sueta at al. (Free Radic. Biol. Med. 41:503-512; 2006) showed, with submitochondrial particles, that>or=3 microM MnIIITE-2-PyP5+ was able to protect components of the mitochondrial electron transport chain from peroxynitrite-mediated damage. Our study complements their data in showing, for the first time that micromolar mitochondrial concentrations of MnIIITE-2-PyP5+ are obtainable in vivo. For this study we have developed a new and sensitive method for MnIIITE-2-PyP5+ determination in tissues. The method is based on the exchange of porphyrin Mn2+ with Zn2+, followed by the HPLC/fluorescence detection of ZnIITE-2-PyP4+. At 4 and 7 h after a single 10 mg/kg intraperitoneal administration of MnIIITE-2-PyP5+, the mice (8 in total) were anesthetized and perfused with saline. Mitochondria were then isolated by the method of Mela and Seitz (Methods Enzymol.55:39-46; 1979). We found MnIIITE-2-PyP5+ localized in heart mitochondria to 2.95 ng/mg protein. Given the average value of mitochondrial volume of 0.6 microL/mg protein, the calculated MnIIITE-2-PyP5+ concentration is 5.1 microM, which is sufficient to protect mitochondria from oxidative damage. This study establishes, for the first time, that MnIIITE-2-PyP5+, a highly charged metalloporphyrin, is capable of entering mitochondria in vivo at levels sufficient to exert there its antioxidant action; such a result encourages its development as a prospective therapeutic agent.
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PMID:Mn porphyrin-based superoxide dismutase (SOD) mimic, MnIIITE-2-PyP5+, targets mouse heart mitochondria. 1738


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