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)

We hypothesized that diabetes and glucose-induced reactive oxygen species lead to depletion of cAMP response element-binding protein (CREB) content in the vasculature. In primary cultures of smooth muscle cells (SMC) high medium glucose decreased CREB function but increased SMC chemokinesis and entry into the cell cycle. These effects were blocked by pretreatment with the antioxidants. High glucose increased intracellular reactive oxygen species detected by CM-H(2)DCFA. SMC exposed to oxidative stress (H(2)O(2)) demonstrated a 3.5-fold increase in chemokinesis (p < 0.05) and accelerated entry into cell cycle, accompanied by a significant decrease in CREB content. Chronic oxidative challenge similar to the microenvironment in diabetes (glucose oxidase treatment) decreases CREB content (40-50%). Adenoviral-mediated expression of constitutively active CREB abolished the increase in chemokinesis and cell cycle progression induced by either high glucose or oxidative stress. Analysis of vessels from insulin resistant or diabetic animals indicates that CREB content is decreased in the vascular stroma. Treatment of insulin-resistant animals with the insulin sensitizer rosiglitazone restores vessel wall CREB content toward that observed in normal animals. In summary, high glucose and oxidative stress decrease SMC CREB content increase chemokinesis and entry into the cell cycle, which is blocked by antioxidants or restoration of CREB content. Thus, decreased vascular CREB content could be one of the molecular mechanisms leading to increased atherosclerosis in diabetes.
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PMID:Diabetes-related changes in cAMP response element-binding protein content enhance smooth muscle cell proliferation and migration. 1156 Sep 25

Long-term complications of diabetes mellitus have been ascribed to both the effects of prolonged hyperglycemia and to increased oxidative stress. In an attempt to identify the mechanisms underlying the acute effects of hyperglycemia on oxidative stress, we investigated the hypothesis that high glucose might lead to an insufficiency in reducing equivalents (such as NADPH) and thus to a disruption in the glutathione-dependent antioxidant defences and to an incapacity to deal with oxidant attack. For this purpose, erythrocytes from diabetic patients were incubated for 0-90 min in 5.55 or 33.3 mM D-glucose containing tertbutyl hydroperoxide 0.5 and 1 mM, Menadione 100 microM, or glucose oxidase. The time course of the changes in non-protein bound glutathione (reduced and oxidised), lactate and pyruvate, alanine and fluorescent products of oxidative proteolysis, hemolysis and methemoglobin was monitored. The results show that although glucose utilisation was unaffected, all oxidants caused a persistent decrease in total non-protein-bound glutathione suggesting binding to proteins. However, changes in glutathione and redox status differed between the various oxidants and were not directly related to the extent of oxidative cellular damage. In these experimental conditions, with short incubations and using the erythrocyte as the simplest cellular model of glucose metabolism, neither high glucose nor the diabetic condition worsened the susceptibility of erythrocytes to acute in vitro oxidative damage.
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PMID:Divergent effects of different oxidants on glutathione homeostasis and protein damage in erythrocytes from diabetic patients: effects of high glucose. 1171 65

Endothelial dysfunction, considered as a defective vascular dilatation after certain stimuli, is characteristic of different pathological conditions, such as hypertension, atherosclerosis, or diabetes. A decreased synthesis or an increased degradation of nitric oxide (NO) has been postulated as the mechanism responsible for this alteration. The present experiments were designed to test the hypothesis that the presence of an abnormal extracellular matrix in vessel walls could be responsible for the decreased NO synthesis observed in these pathological conditions. Experiments were performed in cultured human umbilical vein endothelial cells (HUVECs) grown on type IV (Col. IV) or type I (Col. I) collagen. Cells seeded on Col. I showed decreased nitrite synthesis, nitric oxide synthase activity, eNOS protein content, and eNOS mRNA expression when compared with cells grown on Col. IV. Moreover, cells grown on Col. I failed to respond to glucose oxidase activation of the eNOS system. In both cases, the changes in the eNOS mRNA expression seemed to depend on the modulation of eNOS promoter activity. The downregulation of eNOS induced by Col. I was blocked by D6Y, a peptide that interferes with the Col. I-dependent signals through integrins, as well as by specific anti-integrin antibodies. Moreover, a decreased activation of integrin-linked kinase (ILK) may explain the effects observed in Col. I-cultured cells because the activity of this kinase was decreased in these cells and ILK modulation prevented the Col. I-induced changes in HUVECs. Taken together, these findings may contribute to explaining the basis of endothelial dysfunction in some vascular diseases.
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PMID:Decreased nitric oxide synthesis in human endothelial cells cultured on type I collagen. 1190 17

Total antioxidant status (TAS) was measured in thirty-five (35) non-insulin-dependent diabetes mellitus (NIDDM) patients aged 40 to 65 (mean +/- SE 49.6 +/- 1.0) years. Patients were on diet and oral hypoglycaemic drug (Daonil) therapy with fasting plasma glucose (FPG) >7.8mmol/l. Similar measurements were carried out in thirty-four apparently healthy individuals within the same age range (mean + SE 46.3 +/- 1.1 years) and FPG <6.4 mmol/L. FPG was measured by glucose oxidase method and TAS by colorimetric method. Comparing the two groups, TAS was significantly reduced in the NIDDM patients (p<0.001). An inverse correlation between FPG and TAS suggests the existence of lower antioxidant defence in uncontrolled NIDDM. A good control of FPG accompanied with antioxidant therapy could help reduce free radical activity and minimise complications associated with increased free radical activity in diabetic patients.
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PMID:Total antioxidant status in non-insulin-dependent diabetes mellitus patients in Ghana. 1192 48

The quantification of glucose by using a multi-channel dissolved oxygen (DO) meter (DOX96) with immobilized glucose oxidase (GOD) and mutarotase (MUT) was performed. An evaluation of the inhibitory activities for alpha-glucosidase (AGH) by modifying our batch-type pseudo-in vivo assay system [Oki et al.; Biol Pharm. Bull., 2000, 232, 1084] was also performed using a DOX96. When 45 U/well GOD and 18.75 U/well MUT were immobilized on the surface of a gelatin membrane on the electrodes, the response shown by the decrease percent of DO (%) obtained with 8 electrode wells in the same row was linear with the glucose concentration up to 3.3 mM and a correlation coefficient larger than 0.9. To estimate the AGH inhibitory activity, AGH-immobilized Sepharose supports in the well of a silent screen plate were used. The IC50 values of acarbose and 1-deoxynojirimycin, a medicinal inhibitor for diabetes, were 0.70 +/- 0.08 microM and 0.40 +/- 0.13 microM, respectively, and coincided well with those by a pseudo-in vivo assay.
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PMID:A novel method for the assay of alpha-glucosidase inhibitory activity using a multi-channel oxygen sensor. 1250 81

The SCGM1 System is designed to allow continuous glucose monitoring in the subcutaneous interstitial fluid for up to 120 h. The system is based on the microdialysis technique and is composed of three components: (1) a disposable Cassette, which contains the microdialysis catheter (with the necessary tubes), an electrochemical flow-through sensor for glucose measurement, and the fluid reservoirs for both the microdialysis perfusate and a reagent solution containing glucose oxidase; (2) the Sensor Unit, which houses the Cassette and is worn by the patient using a belt pack; and (3) the Data Manager, with an integrated blood glucose meter for the calibration of the glucose signal. The Data Manager also has the option of displaying the continuous glucose signal. The Sensor Unit and Data Manager exchange glucose data and calibration data by radio transmission. In vitro precision was assessed by measurements of two standard glucose solutions (90 mg/dL, 3.4%; 360 mg/dL, 2.4%) over a time course of 4 days. The mean difference (+/- SD) between SCGM1 System devices (n = 11) and 15 glucose standard solutions with different concentrations was 1.4 +/- 3.5 mg/dL. The mean relative difference and the mean absolute relative difference ranged from - 0.6% to 3.7% and from 0.2% to 3.8%, respectively. The inherent physical lag time was 31 +/- 2 min (n = 10). The interference on the glucose signal of ascorbic acid, acetaminophen, and uric acid at the highest physiological concentrations was below 4%. The SCGM1 System showed a reliable and precise performance under in vitro conditions.
Diabetes Technol Ther 2003
PMID:The SCGM1 System: subcutaneous continuous glucose monitoring based on microdialysis technique. 1451 14

A study was undertaken to determine a reference value for fasting plasma glucose in a group of apparently normal pregnant Nigerian women. Three hundred and twenty women were tested; 260 pregnant and 60 non-pregnant. There were 60, 100 and 100 subjects in the first, second and third trimesters, respectively. Fasting plasma glucose was measured in each of the women using the glucose oxidase method. The mean fasting plasma glucose level was 4.64 +/- 0.79 mmol/l in the control group and 3.72 +/- 0.58, 3.78 +/- 0.81 and 3.81 +/- 0.85 mmol/l in the first, second and third trimesters of pregnancy, respectively. Mean fasting plasma glucose+2 standard deviations (SD) of all the pregnant women was 5.3 mmol/l, which is much lower than the World Health Organisation value for the diagnosis of diabetes mellitus.
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PMID:Fasting plasma glucose levels in normal pregnant Nigerians. 1461 67

Coagulative function of saliva derives from the thromboplastin found in saliva. It may establish hemostasis in the mouth. Salivary disfunction and changes in salivary composition and are frequent complications of diabetes. This study investigated the influence of some local etiologic and systemic factors on salivary thromboplastic activity (STA) in diabetics. In this study, cytological smears and biochemical tests were used. STA was measured by Quick's one stage method, serum glucose by the glucose oxidase method, and salivary protein by the method of Lowry. STA was almost the same in the diabetic and control groups. The only statistically significant difference within the diabetic group was found to be due to antibiotic usage. STA, i.e. clotting time, was 30% longer (114 s) ( p<0.05) and salivary protein (4.07 mg ml(-1)) ( p<0.1) was lower in diabetics not taking antibiotics than in those taking them. No such differences were observed in the healthy controls. Significant linear correlations ( p<0.05) with respect to STA were with salivary protein in the control group (r=0.61) and in the diabetic group (r=0.51) and with antibiotic usage (r=0.29), with leukocyte cell count (r=0.27) in the diabetic group. It can be concluded that salivary cells, proteins and antibiotic usage are important for STA.
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PMID:Salivary thromboplastic activity in diabetics and healthy controls. 1465 32

Glucose is not detectable in airways secretions of normoglycaemic volunteers, but is present at 1-9 mmol x l(-1) in airways secretions from people with hyperglycaemia. These observations suggest the existence of a blood glucose threshold at which glucose appears in airways secretions, similar to that seen in renal and salivary epithelia. In the present study we determined the blood glucose threshold at which glucose appears in nasal secretions. Blood glucose concentrations were raised in healthy human volunteers by 20% dextrose intravenous infusion or 75 g oral glucose load. Nasal glucose concentrations were measured using modified glucose oxidase sticks as blood glucose concentrations were raised. Glucose appeared rapidly in nasal secretions once blood glucose was clamped at approx. 12 mmol x l(-1) ( n =6). On removal of the clamp, nasal glucose fell to baseline levels in parallel with blood glucose concentrations. An airway glucose threshold of 6.7-9.7 mmol x l(-1) was identified ( n =12). In six subjects with normal glucose tolerance, blood glucose concentrations rose above the airways threshold and nasal glucose became detectable following an oral glucose load. The presence of an airway glucose threshold suggests that active glucose transport by airway epithelial cells normally maintains low glucose concentrations in airways secretions. Blood glucose exceeds the airway threshold after a glucose load even in people with normal glucose tolerance, so it is likely that people with diabetes or hyperglycaemia spend a significant proportion of each day with glucose in their airways secretions.
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PMID:Effect of hyperglycaemia on glucose concentration of human nasal secretions. 1467 9

The preparation of an enzyme-dispersed carbon-nanotube (CNT) electrode, based on mixing glucose oxidase (GOx) within CNT, is described. The new binderless biocomposite was packed within a 21-gauge needle and used for amperometric monitoring of glucose. The resulting microsensor offers a low-potential highly selective and sensitive detection of glucose. The high sensitivity and selectivity are coupled to a wide linear range, prolonged lifetime and oxygen independence. About 80% of the GOx activity is retained during a 24 h thermal stress at 90 degrees C, reflecting the enzyme-stabilization action of CNT. The marked electrocatalytic action towards hydrogen peroxide allows highly selective detection of the glucose substrate at -0.1 V (vs. Ag/AgCl) with no interferences from coexisting ascorbic acid, acetaminophen or uric acid. Linearity prevails up to 40 mM glucose (with analytically useful signals observed up to 0.1 M). Factors affecting the performance of the CNT-based glucose biosensor were assessed and optimized. The attractive performance of the new needle electrode offers great promise for continuous monitoring of glucose in connection to the management of diabetes, and for the biosensing of other metabolites.
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PMID:Enzyme-dispersed carbon-nanotube electrodes: a needle microsensor for monitoring glucose. 1470 Feb 33


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