Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Endothelial progenitor cells (EPCs) are essential in vasculogenesis and wound healing, but their circulating and wound level numbers are decreased in diabetes. This study aimed to determine mechanisms responsible for the diabetic defect in circulating and wound EPCs. Since mobilization of BM EPCs occurs via eNOS activation, we hypothesized that eNOS activation is impaired in diabetes, which results in reduced EPC mobilization. Since hyperoxia activates NOS in other tissues, we investigated whether hyperoxia restores EPC mobilization in diabetic mice through BM NOS activation. Additionally, we studied the hypothesis that impaired EPC homing in diabetes is due to decreased wound level stromal cell-derived factor-1alpha (SDF-1alpha), a chemokine that mediates EPC recruitment in ischemia. Diabetic mice showed impaired phosphorylation of BM eNOS, decreased circulating EPCs, and diminished SDF-1alpha expression in cutaneous wounds. Hyperoxia increased BM NO and circulating EPCs, effects inhibited by the NOS inhibitor N-nitro-L-arginine-methyl ester. Administration of SDF-1alpha into wounds reversed the EPC homing impairment and, with hyperoxia, synergistically enhanced EPC mobilization, homing, and wound healing. Thus, hyperoxia reversed the diabetic defect in EPC mobilization, and SDF-1alpha reversed the diabetic defect in EPC homing. The targets identified, which we believe to be novel, can significantly advance the field of diabetic wound healing.
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PMID:Diabetic impairments in NO-mediated endothelial progenitor cell mobilization and homing are reversed by hyperoxia and SDF-1 alpha. 1747 53

The influence of angiotensin-converting enzyme on endotheliun-dependent contractile vascular reactions was investigated on the rat model of streptozotocin-induced diabetes mellitus. It is shown, that the long-term administration of enalapril results in partial restoration of disturbed at diabetes mellitus reactions and also to reduction of oxygen cost of smooth muscles and myocardial work. Thus, after 28-day's of oral administration of this drug the restoration of endotheliun-dependent dilatation of aorta and coronary vessels, increase of stretch-induced contractile responses of vascular smooth muscles, reduction of stiffness of isolated portal vein strips are observed. Possible mechanisms of such changes are following: increase of nitric oxide synthesis (at the expense of constitutive NOS activity) and reduction of oxidative stress, to what the decrease of diene conjugates contents in tissues of animals with diabetes mellitus after long introduction of enalapril testifies.
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PMID:[Effect of enalapril on endotheliun-dependent contractile reactions and oxygen cost of work of the smooth muscles in experimental diabetes mellitus]. 1750 Jan 96

We determined whether nitric oxide (NO) counters the development of hypertension at the onset of diabetes in mice, whether this is dependent on endothelial NO synthase (eNOS), and whether non-NO endothelium-dependent vasodilator mechanisms are altered in diabetes in mice. Male mice were instrumented for chronic measurement of mean arterial pressure (MAP). In wild-type mice, MAP was greater after 5 wk of N(omega)-nitro-L-arginine methyl ester (L-NAME; 100 mg x kg(-1) x day(-1) in drinking water; 97 +/- 3 mmHg) than after vehicle treatment (88 +/- 3 mmHg). MAP was also elevated in eNOS null mice (113 +/- 4 mmHg). Seven days after streptozotocin treatment (200 mg/kg iv) MAP was further increased in L-NAME-treated mice (108 +/- 5 mmHg) but not in vehicle-treated mice (88 +/- 3 mmHg) nor eNOS null mice (104 +/- 3 mmHg). In wild-type mice, maximal vasorelaxation of mesenteric arteries to acetylcholine was not altered by chronic L-NAME or induction of diabetes but was reduced by 42 +/- 6% in L-NAME-treated diabetic mice. Furthermore, the relative roles of NO and endothelium-derived hyperpolarizing factor (EDHF) in acetylcholine-induced vasorelaxation were altered; the EDHF component was enhanced by L-NAME and blunted by diabetes. These data suggest that NO protects against the development of hypertension during early-stage diabetes in mice, even in the absence of eNOS. Furthermore, in mesenteric arteries, diabetes is associated with reduced EDHF function, with an apparent compensatory increase in NO function. Thus, prior inhibition of NOS results in endothelial dysfunction in early diabetes, since the diabetes-induced reduction in EDHF function cannot be compensated by increases in NO production.
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PMID:Endothelial dysfunction and arterial pressure regulation during early diabetes in mice: roles for nitric oxide and endothelium-derived hyperpolarizing factor. 1752 17

The purpose of the study was to investigate changes of endothelial function at experimental diabetes mellitus under the action of interval hypoxic trainings (IHT). A decrease of hyperglycemia and normalization of endothelium-dependent vascular reactions are shown after IHT. Activity of constitutive NOS in the heart after IHT increases considerably while activity of inducible NOS decreases sharply. Considerable diminution of iNOS activity after IHT also registered in aorta. Nitrite-anion content (NO2-) increased both in the heart and in aorta. IHT results in diminishing level of such markers of oxidizing stress as a hydrogen peroxide and dien conjugates. Thus, the action of IHT consist in diminishing ofhyperglycemia, decline of expressed of oxidizing stress, partial normalization of synthesis of nitric oxide and renewal of endothelial function in rats with experimental diabetes.
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PMID:[Normalizing effect of intermittent hypoxic training on the function of endothelium in experimental diabetes mellitus]. 1759 5

Endothelial cells (ECs) which participate the interface between the blood and the vessel wall undergo morphologic changes in response to shear stress induced by blood flow, liable for the important regulation on physiologic and pathophysiologic function of blood vessels. Shear stress induced changes in cell morphology, begin with elongation in the direction of shearing and end by a reorientation and assembly of F-actin stress fibers. Shear stress is also implicated in many important ECs functions such as: decrease of platelet aggregation, anti-thrombogenic and anti-adhesive effects, inhibition of vascular smooth muscle cell (SMC) proliferation and regulation of their contraction and arterial tonicity, via a regulation of vasodilator and vasoconstrictor secretion molecules such as nitric oxide (NO), endothelin I, prostacyclin and angiotensin II. Besides, many of human diseases such as hypercholesterolemia, diabetes and hypertension, are strongly linked to a disturbance of the production of several vasodilator or vasoconstrictor molecules. The aim of this in-vitro study was to evaluate the potential balance between time and rate effects of shearing in cell shape changes and e-NOS activity. Two unidirectional steady laminar flow rates (1.2 Pa and 2.0 Pa) were applied on EC monolayers, each one for a short and a long period, (6 h and 24 h). Cytoskeleton reorganization was evaluated by actin filaments labelling and observed by confocal microscopy. NO production was evaluated by a colorimetric method using the Griess reagent kit for nitrite determination. Results showed that laminar flow affected cell rearrangement by inducing cytoskeleton reorientation and increased production of NO. Laminar shear rate at 2.0 Pa for 24 h did not upregulate NO release. Whereas at 1.2 Pa for 24 h, NO release increased by 33% compared with the static conditions. Both 1.2 Pa and 2.0 Pa for 6 h increased NO release by 17% and 24% respectively as compared with the static conditions. These observations suggested that stress fiber assembly, which controls EC reorientation and NO production, are dependent on rate and time of shearing. In addition, there appear to be a relation between the cytoskeleton reorganization stage and NO production. These results could promote the parameters to evaluate the more appropriate pattern of shearing, to evaluate a potential pharmacological effect on hypertension disorder decrease.
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PMID:Potential relation between cytoskeleton reorganization and e-NOS activity in sheared endothelial cells (Effect of rate and time of exposure). 1764 3

Hyperglycaemia is a primary cause of vascular complications in diabetes. A hallmark of these vascular complications is endothelial cell dysfunction, which is partly due to reduced production of nitric oxide. The aim of this study was to verify the influence of improved glycaemic control with chlorpropamide on microvascular reactivity, endothelial nitric oxide synthase (e-NOS) expression, and NOS activity in neonatal streptozotocin-induced diabetic rats (n-STZ). Diabetes was induced by STZ injection into neonates Wistar rats. n-STZ diabetic rats were treated with chlorpropamide (200 mg kg(-1), 15 days, by gavage). The changes in mesenteric arteriolar and venular diameters were determined in anaesthetized control and n-STZ diabetic rats, before and after topical application of acetylcholine, bradykinin and sodium nitroprusside (SNP). We also assessed e-NOS expression (using polymerase chain reaction after reverse transcription of mRNAs into cDNAs) and NOS activity (conversion of L-arginine to citrulline) in the mesenteric vascular bed of chlorpropamide-treated n-STZ, vehicle-treated n-STZ, and control rats. In n-STZ, chlorpropamide treatment reduced high glycaemic levels, improved glucose tolerance and homoeostatic model assessment (HOMA-beta), and restored NOS activity. Impaired vasodilator responses of arterioles and venules to acetylcholine, bradykinin and SNP were partially corrected by chlorpropamide treatment in n-STZ. We concluded that improved metabolic control and restored NOS activity might be collaborating with improved microvascular reactivity found in chlorpropamide-treated n-STZ.
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PMID:The influence of improved glycaemic control with chlorpropamide on microvascular reactivity and nitric oxide synthase activity in diabetic rats. 1772 54

Diabetic patients reveal significant disorders, such as nephropathy, cardiomyopathy, and neuropathy. As oxidative stress and inflammation seem to be implicated in the pathogenesis of diabetic brain, we aimed to investigate the effects of caffeic acid phenethyl ester (CAPE) on oxidative stress and inflammation in diabetic rat brain. Diabetes was induced by a single dose of streptozotocin (45 mg kg(-1), i.p.) injection into rats. Two days after streptozotocin treatment 10 microM kg(-1) day(-1) CAPE was administrated and continued for 60 days. Here, we demonstrate that CAPE significantly decreased the levels of nitric oxide and malondialdehyde induced by diabetes, and the activities of catalase, glutathione peroxidase, and xanthine oxidase in the brain. However, glutathione levels were increased by CAPE. The mRNA expressions of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma, and inducible nitric oxide synthase (iNOS) were remarkably enhanced in brain by diabetes. CAPE treatments significantly suppressed these inflammatory cytokines (about 70% for TNF-alpha, 26% for IFN-gamma) and NOS (completely). Anti-inflammatory cytokine IL-10 mRNA expression was not affected by either diabetes or CAPE treatments. In conclusion, diabetes induces oxidative stress and inflammation in the brain, and these may be contributory mechanisms involved in this disorder. CAPE treatment may reverse the diabetic-induced oxidative stress in rat brains. Moreover, CAPE reduces the mRNA expressions of TNF-alpha and IFN-gamma in diabetic brain; suggesting CAPE suppresses inflammation as well as oxidative stress occurred in the brain of diabetic patients.
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PMID:Caffeic acid phenethyl ester (CAPE) protects brain against oxidative stress and inflammation induced by diabetes in rats. 1826 48

The aim of the presented experiments was to study the influence of suturated NAE--N-stearoylethanolamine (NSE) on the NO synthesis by NO-synthases in aorta and heart tissues of rats with developmental (12-week) streptozotocin-induced (50 mg/kg of body weight) diabetes. Also we evaluated the state of endothelium-dependent relax reactions of aorta smooth muscles. It was shown that the development of diabetes is accompanied with disbalance of NO-synthesis wich consist in inducible NOS (iNOS) activation and inhibition of constitutive NOS (cNOS) and arginase activities. The aorta smooth muscle endothelium-dependent relax reactions were decreased in diabetic rats. The NSE administration to rats with development streptozotocin-induced diabetes resulted in inhibition of iNOS activity and elevation of cNOS and arginase activities in these tissues. Normalization of NO-synthesis under NSE action was accompanied with restoration of aorta smooth muscle endothelium-dependent relax reactions in diabetic rats.
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PMID:[The effects of n-stearoylethanolamine on the NO-synthase pathway of NO generation in the aorta and heart of streptozotocin-induced diabetic rats]. 1835 89

Contrary to clinical trials, experimental studies revealed that diabetes mellitus (DM) may initiate, besides increased myocardial vulnerability to ischemia-reperfusion injury (I/R) and pro/antioxidant dysbalance, development of adaptation leading to an enhanced tolerance to I/R. The aims were to characterize 1) susceptibility to ischemia-induced ventricular arrhythmias in the diabetic rat heart 2) its response to antioxidant N-acetylcysteine (NAC) and a NOS inhibitor L-NAME, and 3) the effect of DM on endogenous antioxidant systems. Seven days after streptozotocin injection (65 mg/kg, i.p.), Langendorff-perfused control (C) and DM hearts were subjected to 30-min occlusion of the LAD coronary artery with or without prior 15-min treatment with L-NAME (100 microM) or NAC (4 mM). Total number of ventricular premature beats (VPB), as well the total duration of ventricular tachycardia (VT) were reduced in the DM group (from 533+/-58 and 37.9+/-10.2 s to 224.3+/-52.6 and 19+/-13.5 s; P<0.05). In contrast to the antiarrhythmic effects of L-NAME and NAC in controls group (VPB 290+/-56 and 74+/-36, respectively; P<0.01 vs. control hearts), application of both drugs in the diabetics did not modify arrhythmogenesis (L-NAME: VPB 345+/-136, VT 25+/-13 s; NAC: VPB 207+/-50, VT 12+/-3.9 s; P>0.05 vs non-treated diabetic hearts). Diabetic state was associated with significantly elevated levels of CoQ10 and CoQ9 (19.6+/-0.8 and 217.3+/-9.5 vs. 17.4+/- 0.5 and 185.0+/-5.0 nmol/g, respectively, in controls; P<0.05), as well as alpha-tocopherol (38.6+/-0.7 vs. 31.5+/-2.1 nmol/g in controls; P<0.01) in the myocardial tissue. It is concluded that early period of DM is associated with enhanced resistance to ischemia-induced arrhythmias. Diabetes mellitus might induce adaptive processes in the myocardium leading to lower susceptibility to antioxidant and L-NAME treatment.
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PMID:The effect of antioxidant treatment and NOS inhibition on the incidence of ischemia-induced arrhythmias in the diabetic rat heart. 1837 92

Dimethyl amiloride (DMA) enhances insulin secretion in the pancreatic beta-cell. DMA also enhances time-dependent potentiation (TDP) and enables TDP to occur in situations where it is normally absent. As we have demonstrated before, these effects are mediated in part through inhibition of neuronal nitric oxide synthase (nNOS), resulting in increased availability of arginine. Thus both DMA and arginine have the potential to correct the secretory defect in diabetes by enabling or enhancing TDP. In the current study we have demonstrated the ability of these agents to improve blood glucose homeostasis in three mouse models of type 2 diabetes. The pattern of TDP under different conditions indicates that inhibition of NOS is not the only mechanism through which DMA exerts its positive effects. Thus we also have explored another possible mechanism through which DMA enables/enhances TDP, via the activation of mitochondrial alpha-ketoglutarate dehydrogenase.
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PMID:Dimethyl amiloride improves glucose homeostasis in mouse models of type 2 diabetes. 1841 72


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