Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We used the partial protection exerted by suitable dosages of nicotinamide against the beta-cytotoxic effect of streptozotocin (STZ) to create an experimental diabetic syndrome in adult rats that appears closer to type II diabetes mellitus than other available animal models. The dosage of 230 mg/kg of nicotinamide given intraperitoneally 15 min before STZ administration (65 mg/kg i.v.) yielded animals with hyperglycemia (187.8 +/- 17.8 vs. 103.8 +/- 2.8 mg/dL in controls; P < 0.001) and preservation of plasma insulin levels. This study assessed the relationship between endothelial dysfunction and agonist-induced contractile responses in such rats. In the thoracic aorta, the acetylcholine (ACh) induced relaxation was significantly reduced and the noradrenaline (NA) induced contractile response was significantly increased in diabetic rats compared with age-matched control rats. In the superior mesenteric artery, the ACh-induced relaxation was similar in magnitude between diabetic and age-matched control rats; however, the ACh-induced endothelium-derived hyperpolarizing factor (EDHF) type relaxation was significantly weaker in diabetic rats than in the controls. The phenylephrine (PE) induced contractile response was not different between the two groups. The plasma concentration of NOx (NO2- + NO3-) was significantly lower in diabetic rats than in control rats. We conclude that vasomotor activities in conduit arteries are impaired in this type II diabetes model.
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PMID:Alterations in vascular endothelial function in the aorta and mesenteric artery in type II diabetic rats. 1505 83

The objectives of this study include comparing the cement thickness and microleakage of Class II ceramic inlays built with three ceramic systems and verifying whether there was a correlation between those two variables. The ceramic systems used include: 1) Heat-pressed (IPS-Empress); 2) CAD-CAM (CEREC 2) and 3) Sintered (Colorlogic). Standardized MOD Class II inlay cavities with one proximal box extending below and the other extending above the cement-enamel junction (CEJ) were prepared in 30 extracted human molars and randomly assigned to three groups. The ceramic inlays were constructed according to manufacturer's instructions and cemented using a dual-cure resin cement (Variolink II). All teeth were mechanically cycled (100,000 cycles, 78N) and thermocycled (700 cycles, 5 degrees C-55 degrees C). After immersion in silver nitrate, the inlays were sectioned mesial-distally and evaluated with an optical microscope (40x). The cement thickness obtained by the Colorlogic system (enamel: 113 +/- 25 microm; dentin: 118 +/- 23 microm) was significantly higher than that obtained by CEREC (enamel: 78 +/- 14 microm; dentin: 87 +/- 13 microm) and Empress (enamel: 65 +/- 15 microm; dentin: 89 +/- 14 microm). Regarding dye penetration, there was no statistical difference among the three ceramic systems in enamel. At the dentin margins, the Colorlogic system resulted in a significantly higher penetration depth compared to CEREC and Empress, which had similar average values. No correlation was found between cement thickness and microleakage either in enamel or dentin for any of the ceramic systems.
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PMID:Correlation between microleakage and cement thickness in three Class II inlay ceramic systems. 1508 34

Increased (intra)renal activity of the renin-angiotensin system may cause a persistent increase in renovascular resistance and intraglomerular pressure in patients with diabetes, thus contributing to the development of diabetic renal damage. The effect of chronic angiotensin II subtype 1 receptor blockade on (intra)renal hemodynamics in patients with type 2 diabetes was examined in a double-blind parallel group study. Patients were treated with 40 mg of olmesartan (n = 19) or placebo (n = 16), and renal hemodynamics were assessed before and after 12 wk of treatment using inulin and para-aminohippurate clearance techniques. Olmesartan significantly reduced 24-h ambulatory systolic and diastolic BP (both P < 0.05). In parallel, effective renal plasma flow increased significantly from 602 +/- 76 to 628 +/- 87 ml/min per 1.73 m(2), whereas filtration fraction and renovascular resistance decreased significantly (all P < 0.05). With placebo treatment, effective renal plasma flow decreased and filtration fraction increased significantly (both P < 0.05). GFR was not affected by both treatments. Active plasma renin concentration increased considerably (P < 0.05) with olmesartan therapy but remained unchanged with placebo treatment. Nitric oxide metabolism (plasma nitrate and nitrite) and asymmetric dimethylarginine blood levels were not affected by olmesartan and placebo therapy. In contrast, plasma 8-isoprostane 15(S)-8-iso-prostaglandin F(2a) concentration, a biochemical marker of oxidative stress, decreased significantly (P < 0.05) with olmesartan treatment. Chronic angiotensin II subtype 1 receptor blockade decreases (intra)renal vascular resistance and increases renal perfusion despite significant BP reduction. In addition, it significantly reduces oxidative stress. These effects of angiotensin II receptor antagonists may contribute to their beneficial long-term renal effects in patients with type 2 diabetes.
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PMID:Chronic angiotensin II receptor blockade reduces (intra)renal vascular resistance in patients with type 2 diabetes. 1571 29

Somatic DNA damage has been linked to coronary artery disease (CAD). However, whether genetic instability is linked to CAD per se or to concomitant potentially genotoxic metabolic and pharmacological factors remains still unclear. The aim of this study was to evaluate the determinants of somatic DNA damage in a large population of patients undergoing coronary angiography. A total of 278 in-hospital patients (215 men, age 61.8+/-0.7 years) were studied by using micronucleus assay (MN) in human lymphocytes, which is one of the most commonly used biomarker for somatic DNA damage. Significant CAD (>50% diameter stenosis) was present in 210 patients (179 men, age 62.3+/-0.7 years). Normal coronary arteries were observed in 68 patients (35 men, age 60.2+/-1.7 years). There were no significant differences between patients with and without CAD, but patients with multivessel disease had the highest MN levels (P=0.01). MN frequency was also found significantly higher in presence of type 2 diabetes (P<0.0001), dyslipidemia (P=0.048) and nitrate therapy (P=0.0002). A significant additive effect was also observed between diabetes and nitrate therapy (P=0.02). On multivariate logistic regression analysis, diabetes [odds ratio=6.8 (95% confidence interval, 3.2-14.5), P<0.0001] and nitrate therapy [odds ratio=2.4 (95% confidence interval, 1.3-4.7), P=0.01] remained the only significant determinants for the 50th percentile of MN (>12 per thousand). These results indicated that diabetes and, to a lesser extent, chronic nitrate therapy are major determinants of somatic DNA instability in patients with CAD. DNA damage might represent an additional pathogenetic dimension and a possible therapeutic target in the still challenging management of coronary artery disease concerning diabetics.
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PMID:Diabetes and chronic nitrate therapy as co-determinants of somatic DNA damage in patients with coronary artery disease. 1573 61

Hyperhomocysteinemia has been identified as independent risk factor for early atherosclerotic vascular disease. The purpose of our study was to investigate the plasma homocystein (Hcy) concentrations and its relationship with lipid peroxidation as thiobarbituric acid reactive substances (TBARS) and nitric oxide (NOx; nitrite plus nitrate) concentrations in age-matched non-obese (n=55) and obese (n=60) female subjects with type 2 diabetes mellitus. Non-obese diabetic patients have significantly higher plasma tHcy and TBARS (p<0.001 and p<0.001), and significantly lower NOx concentrations than the controls (n=25) (p<0.001). The plasma tHcy and TBARS concentrations were higher and nitric oxide concentrations were lower in obese diabetics than in non-obese diabetics (for each comparison; p<0.001). Correlation analysis demonstrated that there was a significant positive correlation between tHcy and TBARS (r=0.452, p<0.01) in diabetics groups. There was no significant correlation between tHcy and plasma NOx, insulin and blood pressure. We thought that Hcy might have a permissive role on the endothelium damage through free radical generating systems and the presence of obesity the free radical induced-damage has been elevated in diabetic patients.
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PMID:Plasma total homocysteine concentrations in obese and non-obese female patients with type 2 diabetes mellitus; its relations with plasma oxidative stress and nitric oxide levels. 1603 31

Recent prospective studies indicate endothelial dysfunction and increased risk for cardiovascular events in patients with serological evidence of multiple infections. Soluble CD14 (sCD 14) plays a key role in the neutralization of lipopolysaccharide (LPS), a well-established bacterial product inducing endothelial dysfunction. Insulin resistance was recently identified as a significant factor influencing circulating sCD 14 concentration. Thus, we investigated the association of circulating sCD14 and endothelial dysfunction in subjects with well-established insulin resistance (patients with type 2 diabetes, n = 40) compared to control non-diabetic subjects (n = 100). To further explore the underlying mechanisms, we also analysed C-reactive protein and circulating NO2-/NO3- and cyclic GMP in the diabetic group. Serum sCD 14 concentration (ELISA) was found to be differently associated with endothelium-dependent vasodilatation (EDVD, high-resolution ultrasound) in diabetic and non-diabetic subjects. In nondiabetic subjects, serum sCD14 and C-reactive protein correlated negatively with EDVD (r = -0.21, p = 0.03, and r = -0.21, p = 0.03, respectively). In a partial correlation analysis, these associations remained significant after controlling for age and weight (sCD 14 and EDVD, r = -0.23, p = 0.023; C-reactive protein and EDVD, r = -0.21, p = 0.03; sCD14 and C-reactive protein, r = 0.30, p = 0.002). In contrast, sCD 14 was positively associated with EDVD in type 2 diabetic patients (r = 0.37, p = 0.019,). Interestingly, sCD14 was also associated with NO2-/NO3- in this group (r = 0.62, p = 0.001, n = 22). EDVD also correlated with cyclic GMP (r = 0.47, p = 0.03, n = 22). In summary, circulating sCD 14 is associated with endothelial function. While in non-diabetic subjects sCD14 behaves as an acute phase reactant, its role in type 2 diabetic patients should be further clarified. These findings need to be confirmed in further studies with larger number of patients.
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PMID:Opposite relationship between circulating soluble CD14 concentration and endothelial function in diabetic and nondiabetic subjects. 1626 80

Triflusal is an antiplatelet drug related to aspirin, with different pharmacological properties and a lower haemorrhagic risk. We aimed at comparing their effects on platelet and endothelial activation in type 2 diabetes mellitus (T2DM). In a randomized, double-blind, parallel group study, we compared the effects of three daily regimens (300, 600, and 900 mg) of triflusal, and aspirin (100mg/day) on urinary 11-dehydro-thromboxane (TX)B(2), index of in vivo platelet activation, ex vivo platelet function using the analyzer PFA-100, plasma von Willebrand factor (vWF), P-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and serum nitrite and nitrate (NO(2)(-)+NO(3)(-)) in 60 T2DM patients. Triflusal induced a dose-dependent reduction in 11-dehydro-TXB(2) and a prolongation of closure time in the presence of collagen plus epinephrine (Coll/Epi-CT). The effects of the highest triflusal dose were not different from those of aspirin. The closure time in the presence of collagen plus ADP (Coll/ADP-CT), ICAM-1, VCAM-1, and NO(2)(-)+NO(3)(-) were not modified either by triflusal or aspirin. Plasma P-selectin and vWF were reduced by triflusal but not by aspirin. In T2DM triflusal causes a profound inhibition of platelet TXA(2) biosynthesis in vivo, acting on different targets involved in the platelet-endothelial cell interactions.
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PMID:Inhibition of thromboxane biosynthesis by triflusal in type 2 diabetes mellitus. 1628 96

Endothelial nitric oxide synthase (eNOS) haplotypes are associated with hypertension (HT) in patients with or without type 2 diabetes mellitus (T2DM). We evaluated the association of eNOS genotypes/haplotypes with the plasma concentrations of nitrite/nitrate (NO(x)), which are products of nitric oxide in HT, T2DM, and T2DM+HT patients. We studied eNOS polymorphisms in the promoter region (T-786C), in exon 7 (Glu298Asp), and in intron 4 (b/a) in 98 controls, 68 patients with HT, 66 patients with T2DM, and 86 patients with T2DM+HT. NO(x) concentrations were assessed using a chemiluminescence assay. No differences were found in genotype/allele distribution among groups. Genotypes were not associated with NO(x) concentrations. The "C-Glu-b" haplotype was more common in controls than in HT/T2DM+HT groups (21% versus 9/5%, respectively, P<0.006). This haplotype was more common in HT and T2DM+HT groups among subjects with high (82+/-38 and 90+/-33 microM, respectively) than with low (35+/-7 and 34+/-7 microM, respectively) NO(x) concentrations. Conversely, the "C-Asp-b" haplotype was more common in HT/T2DM+HT groups than healthy (21/21% versus 10%, respectively, P<0.006). The haplotype associated with lower risk of developing hypertension is also associated with higher NO(x) levels among hypertensives. Conversely, the haplotype increasing the risk of developing hypertension is associated with lower NO(x) levels in hypertensives.
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PMID:Influence of eNOS haplotypes on the plasma nitric oxide products concentrations in hypertensive and type 2 diabetes mellitus patients. 1730 74

Short nucleotide repetitions (STRs) are commonly used as genetic markers; thus their detection and analysis constitutes a very important tool for the mapping of genetic diseases, as well as for gathering information about genetic polymorphisms at the population level. STRs can be detected with agarose- or acrylamide-based electrophoretic techniques, followed by visualization of the DNA sample with ethidium bromide, silver nitrate, or fluorophore labeling. In this work, we analyzed genomic DNA from five individuals affected with type II diabetes mellitus (T2DM) and five controls (unaffected individuals) in order to know the most precise and reproducible technique for the analysis of the existing polymorphism in the STR DG10S478 of the TCF7L2 gene. The combination of PCR with labeling of the products with the CY5 fluorophore, followed by detection on an ALFexpress sequencer, offered the required resolution to detect the variability in this STR, based solely on size analysis. Our methodology offers similar accuracy and reproducibility at lower costs than existing methods based on the sequencing of PCR products, and is a faster alternative when applied to genotyping studies.
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PMID:Electrophoretic techniques applied to the detection and analysis of the human microsatellite DG10s478. 1816 73

The aim of this study was to evaluate whether abnormal endothelial function is present in early stages of diabetes, such as impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). Endothelial function was assessed by measuring flow-mediated dilatation and nitrate-induced dilatation of the brachial artery using high-resolution ultrasound. Fasting serum lipid levels were determined, and glucose and insulin values in response to a 75-g oral glucose load were also measured. The results showed the following new findings: (1) compared with subjects with normal glucose tolerance, those with IFG and IGT had impaired flow-mediated dilatation, more remarkable in subjects with type 2 diabetes mellitus than those with IFG and IGT, and (2) flow-mediated dilatation was inversely and strongly related to the extent of hyperglycemia. In conclusion, endothelial dysfunction is present in subjects with IGT and IFG, indicating endothelial damage in these stages.
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PMID:Endothelial dysfunction in impaired fasting glycemia, impaired glucose tolerance, and type 2 diabetes mellitus. 1867 13


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