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)

The objective of our study was to assess the association of eNOS4 and eNOS296 polymorphisms of endothelial nitric oxide synthase (eNOS) gene with obstructive sleep apnea syndrome (OSAS). Forty-eight patients with OSAS and 181 healthy volunteers were included in the study. Genotype analyses were performed for eNOS intron 4 VNTR and exon 7, Glu298Asp (G --> T) polymorphisms. There was no significant difference between the patients and controls regarding eNOS4 polymorphism (P > 0.05). There was a significant difference between the patients and controls regarding eNOS296 polymorphism. Glu/Asp variant was more frequent whereas Glu/Glu variant was less frequent in the patients compared to controls (P < 0.001). There was no relationship between eNOS4 and eNOS296 polymorphisms and polysomnography parameters, apnea-hypopnea index, age, gender, body weight and height, body mass index, hypertension, coronary artery disease, arrhythmia, diabetes mellitus, hypercholesterolemia and smoking (P > 0.05). The eNOS4 polymorphism of NOS gene is not associated with OSAS. However, eNOS296 polymorphism of NOS gene is associated with occurrence of OSAS, but not with severity of OSAS.
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PMID:Role of nitric oxide synthase gene intron 4 and exon 7 polymorphisms in obstructive sleep apnea syndrome. 1865 Nov 56

We investigated the influence of multiple introductions of NO precursor L-arginine and NOS non-selective blocker N-nitroL-arginine (NNLA) on thymic morpho-functional status in Wistar male rats with experimental diabetes mellitus (EDM). To reveal insulin-expressing, proliferating, Treg-cells, iNOS(+)-cells and Bcl-2(+)-cells, the immunohistochemical methods of direct and indirect immunofluorescence with monoclonal antibodies to insulin, PCNA, CD-25 antigen. Bcl-2 and iNOS of rat were used. It was established that NNLA administration to rats with EDM has more pronounced effect in comparison with L-arginine administration, demonstrating an increase in the number of Treg-cells, insulin-expressing and proliferating thymocytes and a decrease in the density of iNOS(+)- and Bcl-2(+)-cells population.
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PMID:[Searching for ways to correct thymic dysfunction in rats with experimental diabetes mellitus]. 1876 77

Chronic kidney disease (CKD) is a major risk factor for the development of cardiovascular disease (CVD). Abnormalities of renal hemodynamics are associated with CKD. Abnormalities in renal hemodynamics include blood flow into glomeruli, and tubulointerstitial tissue. Renin-angiotensin system, oxidative stress and NOS system affect abnormalities of renal hemodynamics in CKD. Further, intrarenal hemodynamic abnormalities are strongly associated with systemic arteriosclerosis. Appropriate regulation of renal hemodynamics and controls of hypertension and diabetes mellitus retard the progression of both CKD and CVD.
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PMID:[Abnormalities in renal hemodynamics]. 1878 95

Asymmetric dimethylarginine (ADMA) and NG-monomethyl- L-arginine ( L-NMMA) are important endogenous endothelial nitric oxide synthase (eNOS) inhibitors. Studies have shown that patients with insulin resistance have elevated plasma levels of ADMA. Moreover, ADMA levels have a prognostic value on long-term outcome of patients with coronary artery disease. Insulin resistance, a disorder associated to inadequate biological responsiveness to the actions of exogenous or endogenous insulin, is a metabolic condition, which exists in patients with cardiovascular diseases. This disorder affects the functional balance of vascular endothelium via changes of nitric oxide (NO) metabolism. Nitric oxide is produced in endothelial cells from the substrate L-arginine via eNOS. Elevated ADMA levels cause eNOS uncoupling, a mechanism which leads to decreased NO bioavailability and increased production of hydrogen peroxide. According to clinical studies, the administration of L-arginine to patients with high ADMA levels improves NO synthesis by antagonizing the deleterious effect of ADMA on eNOS function, although in specific populations such as diabetes mellitus, this might even been harmful. More studies are required in order to certify the role of NOS inhibitors in insulin resistance and endothelial dysfunction. It is still difficult to say whether increased ADMA levels in certain populations is only a reason or the result of the molecular alterations, which take place in vascular disease states.
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PMID:Asymmetric dimethylarginine (ADMA) and other endogenous nitric oxide synthase (NOS) inhibitors as an important cause of vascular insulin resistance. 1879 79

Endothelial nitric oxide synthase (eNOS) activation with subsequent inducible NOS (iNOS), cytosolic phospholipase A2 (cPLA2), and cyclooxygenase-2 (COX2) activation is essential to statin inhibition of myocardial infarct size (IS). In the rat, the peroxisome proliferator-activated receptor-gamma agonist pioglitazone (Pio) limits IS, upregulates and activates cPLA2 and COX2, and increases myocardial 6-keto-PGF1alpha levels without activating eNOS and iNOS. We asked whether Pio also limits IS in eNOS-/- and iNOS-/- mice. Male C57BL/6 wild-type (WT), eNOS-/-, and iNOS-/- mice received 10 mg.kg(-1).day(-1) Pio (Pio+) or water alone (Pio-) for 3 days. Mice underwent 30 min coronary artery occlusion and 4 h reperfusion, or hearts were harvested and subjected to ELISA and immunoblotting. As a result, Pio reduced IS in the WT (15.4+/-1.4% vs. 39.0+/-1.1%; P<0.001), as well as in the eNOS-/- (32.0+/-1.6% vs. 44.2+/-1.9%; P<0.001) and iNOS-/- (18.0+/-1.2% vs. 45.5+/-2.3%; P<0.001) mice. The protective effect of Pio in eNOS-/- mice was smaller than in the WT (P<0.001) and iNOS-/- (P<0.001) mice. Pio increased myocardial Ser633 and Ser1177 phosphorylated eNOS levels in the WT and iNOS-/- mice. iNOS was undetectable in all six groups. Pio increased cPLA2, COX2, and PGI2 synthase levels in the WT, as well as in the eNOS-/- and iNOS-/-, mice. Pio increased the myocardial 6-keto-PGF1alpha levels and cPLA2 and COX2 activity in the WT, eNOS-/-, and iNOS-/- mice. In conclusion, the myocardial protective effect of Pio is iNOS independent and may be only partially dependent on eNOS. Because eNOS activity decreases with age, diabetes, and advanced atherosclerosis, this effect may be relevant in a clinical setting and should be further characterized.
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PMID:Pioglitazone protects the myocardium against ischemia-reperfusion injury in eNOS and iNOS knockout mice. 1893 Oct 27

Participation in regular exercise training improves dorsal skin perfusion, while type 2 diabetes mellitus (T2 DM) often limits it via reductions in the action or release of vasodilatory compounds. This study was undertaken to investigate the relative contributions of prostaglandins (PG), nitric oxide (NO), and endothelial-derived hyperpolarizing factor (EDHF) in dorsal foot skin perfusion in individuals with and without T2 DM and a sedentary lifestyle. Participants included 24 individuals with T2 DM and 28 nondiabetic controls whose exercise status was determined via questionnaire. Their dorsal foot skin perfusion was measured at rest using laser Doppler assessment during localized heating to 44 degrees C with oral aspirin (ASA, 325 mg) treatment. In addition, they received an infusion via a subcutaneous microdialysis probe of either saline (left foot) or L-NAME, a NOS-inhibitor (right foot). Compared to normative data without ASA, heat-stimulated perfusion in regular exercisers (n=22) was significantly more suppressed by ASA and by ASA/L-NAME than in sedentary individuals (n=30). Chronic exercisers exhibit a greater reliance on PG and lesser involvement of EDHF with unchanged NO compared to sedentary individuals, who rely more on EDHF and less on PG release. One possible exception may be diabetic, sedentary individuals, who may rely somewhat more on NO than EDHF. These results suggest that regular exercise may exhibit the greatest effect on the normal functioning of these vasodilatory pathways, although diabetes and a sedentary state together may somewhat alter their relative importance.
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PMID:Exercise status affects skin perfusion via prostaglandin, nitric oxide, and EDHF pathways in diabetes. 1910 Jul 52

The mechanism by which insulin causes vasodilatation remains unclear, so we explored this in aortic rings from normal Wistar Kyoto and streptozotocin-induced diabetic rats. Insulin-induced relaxation of phenylephrine-contracted [endothelium (ED) intact or denuded] aortic rings was recorded in the presence or absence of various drug probes. Insulin relaxant effect was more in ED-intact than in-denuded tissues from normal or diabetic rats. l-NAME or methylene blue partially inhibited insulin effect in ED-intact but not the ED-denuded tissues, whereas indomethacin (cyclooxygenase inhibitor) had no effect on any of the tissues, indicating that insulin induces relaxation by ED-dependent and -independent mechanisms, the former via the NOS-cyclic guanosine monophosphate but not the cyclooxygenase pathway. The voltage-dependent K channel (KV) blocker (4-aminopyridine) inhibited insulin action in all the tissues (normal or diabetic, with or without ED), whereas the selective BKCa blocker, tetraethylammonium, inhibited it in normal (ED intact or denuded) but not in diabetic tissues, indicating that KV mediates insulin action in normal and diabetic tissues, whereas the BKCa mediates it only in normal tissues, with possible pathophysiologic absence in diabetic tissues. The inward rectifier K channel (Kir) blocker (barium chloride) significantly inhibited insulin effect only in ED-intact or -denuded diabetic tissues, whereas the KATP channel blocker, glibenclamide, inhibited it only in the ED-denuded diabetic tissues, suggesting that Kir channels mediate insulin-induced relaxation in ED-intact or -denuded diabetic tissues, whereas the KATP channel mediates it in ED-denuded diabetic tissues. All the agents combined did not abolish insulin action, suggestive of a direct vasodilatory effect. In conclusion, insulin causes vasodilatation in normal and diabetic tissues via ED-dependent and -independent mechanisms differentially modulated by K channels, some of which functions are altered in diabetes and thus are potential therapeutic targets.
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PMID:Characterizing the mechanisms of insulin vasodilatation of normal and streptozotocin-induced diabetic rat aorta. 1929 43

The development of the atherosclerosis is based on multifactorial causes. In addition to the traditional risk factors, gene polymorphisms can play a role in the disease. Therefore in this study we investigated whether the eNOS and MTHFR gene polymorphisms is associated with myocardial infarction and stroke in patients with or without diabetes. We have identified polymorphisms in the NOS 3 gene and one of these polymorphisms, Glu(298-->)Asp, was found to be a major risk factor for carotid artery disease and myocardial infarction. Our results indicate that the MTHFR G677T allele is significantly associated with MI. MTHFR 677 G/T genotyping may be of clinical importance as a prognostic and therapeutic marker, although further studies are needed to substantiate this hypothesis.
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PMID:Methylentetrahydrofolate reductase and nitric oxide synthase polymorphism in patients with atherosclerosis and diabetes. 1933 Apr 66

Refractory wound is a severe complication that leads to limb amputation in diabetes. Endothelial nitric oxide synthase (eNOS) plays a key role in normal wound repair but is uncoupled in streptozotocin (STZ)-induced type 1 diabetes because of reduced cofactor tetrahydrobiopterin (BH(4)). We tested the hypothesis that overexpression of GTP cyclohydrolase I (GTPCH I), the rate-limiting enzyme for de novo BH(4) synthesis, retards NOS uncoupling and accelerates wound healing in STZ mice. Blood glucose levels were significantly increased in both male endothelium-specific GTPCH I transgenic mice (Tg-GCH; via a tie-2 promoter) and wild-type (WT) littermates 5 days after STZ regimen. A full-thickness excisional wound was created on mouse dorsal skin by a 4-mm punch biopsy. Wound closure was delayed in STZ mice, which was rescued in STZ Tg-GCH mice. Cutaneous BH(4) level was significantly reduced in STZ mice vs. WT mice, which was maintained in STZ Tg-GCH mice. In STZ mice, constitutive NOS (cNOS) activity and nitrite levels were decreased compared with WT mice, paralleled by increased superoxide anion (O(2)(-)) level and inducible NOS (iNOS) activity. In STZ Tg-GCH mice, nitrite level and cNOS activity were potentiated and O(2)(-) level and iNOS activity were suppressed compared with STZ mice. Thus endothelium-specific BH(4) overexpression accelerates wound healing in type 1 diabetic mice by enhancing cNOS activity and suppressing oxidative stress.
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PMID:Endothelium-specific GTP cyclohydrolase I overexpression accelerates refractory wound healing by suppressing oxidative stress in diabetes. 1933 62

Erectile dysfunction (ED) is a major complication of diabetes mellitus (DM). This study investigates the relationship between ED and the downregulation of constitutive nitric oxide synthase (cNOS) in the corpus cavernosum (CC) of diabetic rats. It also examines the effects of udenafil, a phosphodiesterase type 5 (PDE5) inhibitor, on ED and cNOS expression levels. After 16 weeks of daily oral treatment with udenafil in diabetic rats, the intracavernous pressure/mean arterial pressure (ICP/MAP) ratio was recorded to measure erectile function, and cNOS expression was measured using reverse transcriptase (RT)-PCR and immunoblots. Although the ICP/MAP ratio and the expression levels of endothelial NOS (eNOS) and neuronal NOS (nNOS) in the CC were markedly decreased in diabetic rats, long-term udenafil treatment improved the erectile function and increased cNOS expression compared with diabetic controls. These findings suggest that ED in DM is closely related to decreased cNOS expression in the CC and that udenafil has the ability to compensate for this pathological change by modulating cNOS expression. Udenafil also has an inhibitory role in cGMP (cyclic guanosine monophosphate) degradation.
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PMID:Increased expression of the nitric oxide synthase gene and protein in corpus cavernosum by repeated dosing of udenafil in a rat model of chemical diabetogenesis. 1946 35


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