UMLS:C0011849 - FACTA Search

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

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

The development of diabetic complications has usually been attributed to the nonenzymic glycation of tissue proteins. Only recently, however, have researchers examined the possible role on free radicals in the pathogenesis of diabetes. In the present study, glutathione (GSH) and major antioxidant enzyme levels in plasma of patients with type II diabetes mellitus were assessed both before and after 3 months of N-acetylcysteine (NAC) therapy. Thirty-two diabetic patients were examined as well as fifteen healthy controls. Before treatment with NAC, glutathione peroxidase (GPx), catalase (CAT), and (GSH) levels of diabetic patients and control subjects showed no significant differences, whereas glutathione S-transferase (GST) levels were higher in type II diabetic patients. Following 3 months of Following NAC supplementation, GSH, GST, and CAT levels were found to be similar to the levels before treatment. On the other hand, GPx activity was significantly lower compared with the values before treatment. According to this finding, NAC treatment could have a positive effect on GPx values in type II diabetic patients showing abnormally high values.
...
PMID:The role of N-acetylcysteine treatment on anti-oxidative status in patients with type II diabetes mellitus. 1733 80

Contrast-induced nephropathy (CIN) is a well-known complication of therapeutic and diagnostic procedures requiring contrast administration and accounts for 10 to 12% of acute renal failure in hospitalized patients. Although the incidence of this complication is relatively low, its consequences can be catastrophic. The development of CIN is associated with increased hospital length of stay, an increased requirement for acute dialysis, and an increased risk of death. Preexisting renal dysfunction, age, diabetes, congestive heart failure, and volume of administered contrast are all associated with a risk of developing CIN. Despite a large number of clinical trials that have evaluated prophylaxis strategies for CIN, only the use of hemofiltration and N-acetylcysteine (NAC) in specific subgroups of patients have been shown to reduce dialysis requirement and mortality in patients undergoing angiographic procedures. In this review we will discuss the epidemiology and the risk factors for CIN and the evidence for commonly employed prophylaxis strategies, and we will provide general recommendations with respect to CIN prevention and management.
...
PMID:Prevention and treatment of contrast-induced nephropathy. 1748 99

We studied whether angiotensin II (ANG II) via superoxide may contribute to retinal leukostasis and thus to the pathogenesis of retinopathies. We studied: 1) whether intravitreal ANG II induces retinal leukostasis that is altered by antioxidants or by apocynin, a NAD(P)H oxidase inhibitor and 2) whether retinal leukostasis induced by diabetes in rats is also altered by these treatments. Rats were injected intravitreally with ANG II (20 microg in 2 microl), and divided into the following three groups: 1) untreated; 2) treated with tempol doses ( approximately 3 mM/day) and N-acetylcysteine (NAC; approximately 1 g.kg(-1).day(-1)); and 3) treated with apocynin ( approximately 2 mM/day), both in the drinking water. Rats with streptozotocin-induced diabetes were similarly treated. Leukostasis was evaluated 48 h after ANG II or 2 wk after diabetes induction. ANG II increased retinal leukostasis from 0.3 +/- 0.5 to 3.7 +/- 0.4 leukocytes/ mm(2) (P < 0.01), and these changes were markedly decreased by treatment with tempol + NAC or apocynin, and also by a blocking antibody against vascular endothelial growth factor given intravitreally (P < 0.01). In addition, incubation of dihydroethidium-loaded retina sections with ANG II caused marked increase in superoxide formation. Compared with normal controls, retinal leukostasis in diabetic rats markedly increased from 0.2 +/- 0.3 to 3.8 +/- 0.1 leukocytes/mm(2) (P < 0.01). Diabetic retinal leukostasis was also decreased by treatment with tempol-NAC and normalized by apocynin. Thus increases in intravitreal ANG II can induce retinal leukostasis, which appears to be mediated via increasing superoxide generation by NAD(P)H oxidase, and by VEGF. The activity of NAD(P)H oxidase is required for leukostasis to occur in the diabetic retina.
...
PMID:Role of NADPH oxidase and ANG II in diabetes-induced retinal leukostasis. 1765 61

Cardiovascular disease (CVD) remains the most common cause of premature death in the chronic kidney disease (CKD) population. Individuals with CKD are at 10-20 times greater risk of cardiac death than controls without CKD, despite stratification for age, race, sex and diabetes. Heightened CVD mortality begins with mild kidney disease and rises further with more advanced kidney disease. Traditional risk factors account for up to 50% of cardiovascular disease in CKD, whilst renal specific markers, including anemia, disordered bone mineral metabolism and oxidative stress, also likely contribute to the total cardiovascular burden in CKD. Despite the increased mortality, there has been a dearth of interventional cardiovascular randomized controlled trials (RCTs) in the CKD population. Furthermore, many patients with kidney disease have been excluded from the majority of mainstream cardiovascular interventional trials. While recently published RCTs on traditional and non-traditional risk factors including dyslipidemia (PPP, 4D and ALERT, VA-HIT), cardiomyopathy (FOSIDIAL, telmisartan, carvedilol), anemia (US Normal Hematocrit, CHOIR and CREATE trials), hyperhomocystenemia (ASFAST, US folic acid trial, HOST), disordered bone mineral metabolism (Cunningham meta-analysis, DCOR), oxidative stress therapy (SPACE, HOPE and ATIC, N-acetylcysteine) and multidisciplinary multiple cardiovascular risk factor intervention clinics (LANDMARK) have added to the available pool of clinical data, level 1 clinical evidence remains significantly lacking. The negative findings in many of these trials highlight the potential dangers of extrapolating findings from non kidney disease patients to those with CKD. Further large, well-designed trials are urgently required to address this issue.
...
PMID:Cardiovascular disease in patients with chronic kidney disease. A clinical review. 1791 25

Glutathione is a small tripeptide to maintain overall reducing environment in vivo. Reduced endogenous glutathione level has been associated with aging, obesity and diabetes. In this study, the direct impact of low endogenous glutathione level on energy homeostasis is investigated at molecular level. Depletion of endogenous glutathione in rat primary hepatocytes by BSO, an inhibitor of gamma-glutamylcysteine synthase, leads to reduced mRNA levels of several key enzymes in energy homeostasis, including phosphoenolpyruvate carboxylkinase (PEPCK), the rate-limiting enzyme in gluconeogenesis. Supplementation of various reducing reagents, including N-acetylcysteine, DTT and glutathione, reverses the inhibitory effect of BSO on PEPCK mRNA level. The suppressive effect of BSO on PEPCK mRNA level is also reversed through co-treatment with either SB210290, a specific p38 kinase inhibitor, or wortmannin and LY294002, the well-established PI-3 kinase inhibitors, suggesting the involvement of these kinases in this process. These observations correlate well with the observations that reduced endogenous glutathione level and reduced gluconeogenesis coincide with aging process, implying a causal relationship between these changes in aged population. More importantly, this study suggests that endogenous glutathione level tightly associates with energy homeostasis at molecular level, identifying reduced endogenous glutathione level as a potential contributing factor to dysregulated metabolic processes in aging, obese and diabetic populations. In addition, the different responses of PEPCK expression to the alteration of endogenous glutathione level in rat hepatoma cells from primary hepatocytes raises caution against using established cell lines in examining the dysregulated metabolic process related to altered endogenous glutathione level.
...
PMID:Suppression of phosphoenolpyruvate carboxykinase gene expression by reduced endogenous glutathione level. 1796 99

Advanced glycation end products (AGEs) promote reactive oxygen species (ROS) formation and oxidant stress (OS) in diabetes and aging-related diseases. AGE-induced OS is suppressed by AGER1, an AGE-receptor that counteracts receptor for advanced glycation end products (RAGE) and epidermal growth factor receptor (EGFR)-mediated Shc/Ras signal activation, resulting in decreased OS. Akt, FKHRL1, and antioxidants; e.g., MnSOD, regulate OS. Serine phosphorylation of p66(shc) also promotes OS. We examined the effects of two defined AGEs N(epsilon)-carboxy-methyl-lysine (CML) and methyl-glyoxal derivatives (MG) on these cellular pathways and their functional relationship to AGER1 in human embryonic kidney cells (HEK293). Stimulation of HEK293 cells with either AGE compound increased phosphorylation of Akt and FKHRL1 by approximately threefold in a redox-dependent manner. The use of p66(shc) mutants showed that the AGE-induced effects required Ser-36 phosphorylation of p66(shc). AGE-induced phosphorylation of FKHRL1 led to a 70% downregulation of MnSOD, an effect partially blocked by a phosphatidylinositol 3-kinase inhibitor (LY-294002) and strongly inhibited by an antioxidant (N-acetylcysteine). These pro-oxidant responses were suppressed in AGER1 overexpressing cells and reappeared when AGER1 expression was reduced by small interfering RNA (siRNA). These studies point to a new pathway for the induction of OS by AGEs involving FKHRL1 inactivation and MnSOD suppression via Ser-36 phosphorylation of p66(shc) in human kidney cells. This represents a key mechanism by which AGER1 maintains cellular resistance against OS. Thus the decrease of AGER1 noted in aging and diabetes may further enhance OS and reduce innate antioxidant defenses.
...
PMID:AGE-receptor-1 counteracts cellular oxidant stress induced by AGEs via negative regulation of p66shc-dependent FKHRL1 phosphorylation. 1803 26

Bidens alba has been used for healing cuts, injuries, swellings, hypertension, jaundice, and diabetes in some countries. However, the effect of B. alba on human cancer remains poorly understood. The goal of this study was to investigate whether B. alba protein-extract could have an anticancer property against human colorectal cancer. The human colorectal cancer SW 480 cells treated with the protein-extract of B. alba would cause marked DNA damages and apoptosis-related cellular morphologies. Treatment with 225 microg/ml B. alba protein-extract also led to the SW480 cells to produce readily intracellular reactive oxygen species (ROS) after 1h of treatment and last to 24 h. The intracellular glutathione (GSH) depletion occurred after 12-24h of treatment. The treatment of the protein-extract would also caused mitochondrial transmembrane potential (DeltaPsi(m)) to decrease and cytosolic cytochrome c to increase. The caspase 3/7 activities were activated from 3 to 6 h after the treatment. The percentages of apoptosis induced by the protein-extract of B. alba decreased 26.4%, 10.1%, and 29.4% when the SW 480 cells were pretreated with Vitamin C, N-acetylcysteine, and Boc-Asp(OMe)-fmk, respectively. Taken together, we demonstrated for the first time that the protein-extract of B. alba could induce apoptosis that was related to the ROS production and GSH depletion in human colorectal cancer. The protein-extract of B. alba might have therapeutic value against the human colorectal cancer.
...
PMID:The anticancer effect of protein-extract from Bidens alba in human colorectal carcinoma SW480 cells via the reactive oxidative species- and glutathione depletion-dependent apoptosis. 1822 50

Hyperglycemia-induced oxidative stress plays a crucial role in the pathogenesis of diabetic complications. Although some clinical evidences suggest the use of pyridoxal-5'-phosphate (PLP) in diabetes with nephropathy, the exact mechanism of PLP has not been fully understood. In the present study, the effect of PLP on 2-deoxy-D-ribose (dRib)-induced oxidative damages and apoptosis on human monocytic cells (U937) was investigated. U937 cells exposed to dRib (30 mM) exhibited abnormal properties, including loss pf cell viability, overproduction of reactive oxygen species (ROS), glutathione depletion and some biochemical features of apoptosis. Treatment with PLP at two effective concentrations (100 and 250 microM) strongly inhibited ROS production and glutathione depletion in dRib-treated U937 cells. The extent of Lipid peroxidation and protein oxidation was also decreased in the presence of PLP. In addition, PLP suppressed dRib-induced apoptotic criteria such as sub-G1 apoptotic population and annexin-V staining. The use of N-acetylcysteine (NAC), a thiol antioxidant and GSH precursor, prevented the extent of apoptosis. The results demonstrate that dRib induces the generation of ROS leading to dRib-mediated apoptosis which can be attenuated by PLP through antioxidant mechanisms.
...
PMID:2-Deoxy-D-ribose-induced oxidative stress causes apoptosis in human monocytic cells: prevention by pyridoxal-5'-phosphate. 1836 60

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.
...
PMID:The effect of antioxidant treatment and NOS inhibition on the incidence of ischemia-induced arrhythmias in the diabetic rat heart. 1837 92

We studied the effects of advanced glycation end products (AGEs), which are known to accumulate in patients with diabetes, autoimmune diseases, or those who smoke, on embryonal development. Pronuclear (PN) embryos were obtained by flushing the fallopian tubes of rats after superovulation and mating. The cleavage rate and blastocyst yield were evaluated at 24, 72, 96, and 120 h of culture. Glyoxal, an AGE-forming aldehyde, suppressed embryonal development at every stage from PN to blastocyst in a concentration-dependent manner. The cleavage rate of the embryo was also signifi cantly decreased by treatment with glyoxal at concentrations of 1 mM or higher. The blastocyst yield was significantly decreased by treatment with glyoxal at concentrations of 0.5 mM or higher. N-acetyl-L-cysteine (L-NAC) at 1 mM significantly suppressed the glyoxal-induced embryonal toxicity. BSA-AGEs at 5 microg/ml or higher concentration signifi cantly reduced the cleavage rate and blastocyst yield compared to those for BSA-treated embryos. L-NAC at 1 mM significantly suppressed BSAAGE-induced embryonal toxicity. Because AGEs are embryo-toxic, AGE contamination may influence the pregnancy rate of in vitro fertilization and embryo transfer. AGEs, which are increased in women under pathological conditions, may also be involved in their infertility.
...
PMID:Adverse effects of advanced glycation end products on embryonal development. 1846 85

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>