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)

Physalis angulata (PA) is employed in herbal medicine around the world. It is used to treat diabetes, hepatitis, asthma and malaria in Taiwan. We have evaluated PA as a cancer chemopreventive agent in vitro by studying the role of PA in regulation of proliferation, cell cycle and apoptosis in human breast cancer cell lines. PA inhibited cell proliferation and induced G2/M arrest and apoptosis in human breast cancer MAD-MB 231 and MCF-7 cell lines. In this study, under treatment with various concentrations of PA in MDA-MB 231 cell line, we checked mRNA levels for cyclin A and cyclin B1 and the protein levels of cyclin A and cyclin B1, Cdc2 (cyclin-dependent kinases), p21(waf1/cip1) and P27(Kip1) (cyclin-dependent kinase inhibitors), Cdc25C, Chk2 and Wee1 kinase (cyclin-dependent kinase relative factors) in cell cycle G2/M phase. From those results, we determined that PA arrests MDA-MB 231 cells at the G2/M phase by (i) inhibiting synthesis or stability of mRNA and their downstream protein levels of cyclin A and cyclin B1, (ii) increasing p21(waf1/cip1) and P27(kip1) levels, (iii) increasing Chk2, thus causing an increase in Cdc25C phosphorylation/inactivation and inducing a decrease in Cdc2 levels and an increase in Wee1 level. According to the results obtained, PA appears to possess anticarcinogenic properties; these results suggest that the effect of PA on the levels of phosphorylated/inactivated Cdc25C are mediated by Chk2 activation, at least in part, via p21(waf1/cip1) and P27(kip1) cyclin-dependent kinase inhibitors pathway to arrest cells at G2/M phase in breast cancer carcinoma cells.
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PMID:Physalis angulata induced G2/M phase arrest in human breast cancer cells. 1642 78

Both experimental and clinical studies suggests that oxidative stress plays an important role in the pathogenesis of diabetes mellitus type 1 and type 2. Hyperglycaemia leads to free radical generation and causes neural degeneration. In the present study we investigated the possible neuroprotective effect of mexiletine against streptozotocin-induced hyperglycaemia in the rat brain and spinal cord. 30 adult male Wistar rats were divided into three groups: control, diabetic, and diabetic-mexiletine treated group. Diabetes mellitus was induced by a single injection of streptozotocin (60 mg/kg body weight). Mexiletine (50 mg/kg) was injected intraperitoneally every day for six weeks. After 6 weeks the brain, brain stem and cervical spinal cord of the rats were removed and the hippocampus, cortex, cerebellum, brain stem and spinal cord were dissected for biochemical analysis (the level of Malondialdehide [MDA], Nitric Oxide [NO], Reduced Glutathione [GSH], and Xanthine Oxidase [XO] activity). MDA, XO and NO levels in the hippocampus, cortex, cerebellum, brain stem and spinal cord of the diabetic group increased significantly, when compared with control and mexiletine groups (P < 0.05). GSH levels in the hippocampus, cortex, cerebellum, brain stem and spinal cord of the diabetic group decreased significantly when compared with control and mexiletine groups (P < 0.05). This study demonstrates that mexiletine protects the neuronal tissue against the diabetic oxidative damage.
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PMID:Neuroprotective effect of mexiletine in the central nervous system of diabetic rats. 1654 Nov 98

Trigonella foenum graecum seed powder (TSP) and Sodium Orthovanadate (SOV) have been shown to demonstrate antidiabetic effects by stabilizing glucose homeostasis and carbohydrate metabolism in experimental type-1 diabetes. However their efficacy in controlling histopathological and biochemical abnormalities in ocular tissues associated with diabetic retinopathy is not known. The purpose of this study was to investigate the comparative efficacy of individual as well as combination therapy of TSP and SOV in 8 weeks diabetic rat lens and retina. Retinas and lenses were taken from control, alloxan-induced diabetic rats and diabetic rats treated separately with insulin, 5%TSP, SOV (0.6 mg/ml) and a combined dose of SOV (0.2 mg/ml) and 5%TSP for 60 days. Control and each experimental group had six rats. Alterations in the activities of enzymes HK (hexokinase), AR (aldose reductase), SDH (sorbitol dehydrogenase), G-6-PD (glucose-6-phosphate dehydrogenase), GPx (glutathione peroxidase), GR (glutathione reductase) and levels of metabolites like sorbitol, fructose, glucose, MDA (malondialdehyde) and GSH (reduced glutathione) were measured in the cytosolic fraction of lenses besides measuring blood glucose levels and glycosylated haemoglobin. Histopathological abnormalities were studied in the lens using photomicrography and retina using transmission electron microscopy. Blood glucose, glycosylated haemoglobin levels and polyol pathway enzymes AR and SDH increased significantly causing accumulation of sorbitol and fructose in the diabetic lens and treatment with SOV and TSP significantly (p < 0.05) decreased these to control levels. Similarly, SOV and TSP treatments modulated the activities of HK, G-6-PD, GPx and GR in the rat lens to control values. Ultrastructure of the diabetic retina revealed disintegration of the inner nuclear layer cells with reduction in rough endoplasmic reticulum and swelling of mitochondria in the bipolar cells; and these histopathological events were effectively restored to control state by SOV and TSP treatments. In this study SOV and TSP effectively controlled ocular histopathological and biochemical abnormalities associated with experimental type-1 diabetes, and a combination regimen of low dose of SOV with TSP demonstrated the most significant effect. In conclusion, the potential of SOV and TSP alone or in low dose combination may be considered as promising approaches for the prevention of diabetic retinopathy and other ocular disorders.
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PMID:Long-term effect of Trigonella foenum graecum and its combination with sodium orthovanadate in preventing histopathological and biochemical abnormalities in diabetic rat ocular tissues. 1671 75

It is well known that hyperglycaemia due to diabetes mellitus leads to oxidative stress in the central nervous system. Oxidative stress plays important role in the pathogenesis of neurodegenerative changes. In the present study we investigated the possible neuroprotective effect of etomidate against streptozotocin-induced (STZ-induced) hyperglycaemia in the rat brain and spinal cord. A total of 40 rats were used in this study. Rats were divided into four groups: sham-control, diabetic, diabetic-etomidate treated and vehicle for etomidate treatment group. Diabetes mellitus was induced by a single injection of streptozotocin (60 mg/kg body weight). Three days after streptozotocin injection, etomidate (2 mg/kg) was injected intraperitoneally for etomidate group and lipid emulsion (10%) for vehicle group was injected with corresponding amount intraperitoneally every day for 6 weeks. Six weeks after streptozotocin injection, seven rats from each group were killed and brain, brain stem and cervical spinal cord were removed. The hippocampus, cortex, cerebellum, brain stem and spinal cord were dissected for the biochemical analysis (the level of malondialdehyde [MDA], total nitrite, reduced glutathione [GSH], and xanthine oxidase [XO] activity). STZ-induced diabetes resulted in significantly elevation of MDA, XO and nitrite levels in the hippocampus, cortex, cerebellum, brain stem and spinal cord of the rats (P < 0.05) while etomidate treatment provided significantly lower values (P < 0.05). This study demonstrated that etomidate have neuroprotective effect on the neuronal tissue against the diabetic oxidative damage.
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PMID:Neuroprotective effect of etomidate in the central nervous system of streptozotocin-induced diabetic rats. 1679 61

Devil's Club, Oplopanax horridus (OH), is a widely used folk medicine in Alaska and British Columbia for treating a variety of ailments including arthritis, fever and diabetes. HPLC profiling shows that numerous compounds are present in the 70% ethanolic extract of OH dry root bark powder. OH extract inhibited K562, HL60, MCF7 and MDA-MB-468 cell growth with the 50% inhibition (IC(50)) estimated at 1/2700, 1/1700, 1/500 and 1/2500 dilutions, respectively. Non-cytotoxic concentrations (<IC(50)) of OH extract combined with non-cytotoxic concentrations (<IC(50)) of camptothecin (CAM) or paclitaxel (PTX) were tested on the tumor cell lines. Of the 19 combinations tested, 9 showed additive or synergistic anti-proliferative effect while the rest showed antagonistic effect. Combination of OH extract at 1/4000 and 1/16,000 dilutions with 0.1 microM of CAM produced additive, anti-proliferative effects on K562 cells, as did 1/2000 and 1/1000 dilutions of OH combined with 2.5 nM of PTX on MCF7, and 1/4000 dilution of OH with 1 nM of PTX on MDA-MB-468 cells. Combination of 1/8000 and 1/4000 dilution of OH with 0.05 microM of CAM showed strong synergistic anti-proliferative effects on HL60 cells. At non-cytotoxic 1/4000 dilution, OH induced 13.1% of HL60 cells to differentiate into granulocytes but had no effect on monocyte/macrophage differentiation. A cell free hydroxyl radical scavenging assay estimated that OH at 1/100, 1/10 and 1/5 dilutions showed activities equivalent to 2.7, 15.7 and 25.6 microM of Trolox, respectively. At non-cytotoxic 1/4000 and 1/2000 dilutions, OH significantly reduced nitric oxide production by lipopolysaccharide activated RAW 264.7 cells (p<0.001). Our data show that the ethanolic extract of OH has anti-proliferative on several cancer cell lines, and has strong antioxidant activity.
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PMID:In vitro anti-proliferative and antioxidant studies on Devil's Club Oplopanax horridus. 1681

Peroxisome proliferator activated-receptor gamma (PPARgamma) binds to peroxisome receptor response elements with its heterodimeric partner, retinoid X receptor, and regulates downstream gene expression. PPARgamma transcriptionally modulates fat metabolism, and receptor agonists have been developed to treat type II diabetes. PPARgamma is also overexpressed in some tumor cell lines and primary tumors, including breast and prostate tumors. Two PPARgamma antagonists, 2-chloro-5-nitro-N-phenylbenzamide (GW9662) and 2-chloro-5-nitro-N-pyridin-4-yl-benzamide (T0070907), represent good lead compounds for radiotracer development. In the current study, four additional halogen substituted analogs were synthesized and evaluated in a whole cell screening assay for PPARgamma binding activity. Two bromine-containing analogs having EC50 values <5 nM were chosen for bromine-76 radiolabeling. Bromine-76-labeled 2-bromo-5-nitro-N-phenyl-benzamide was selected for subsequent in vitro and in vivo studies due to its superior radiolabeling yield (approximately 70%) and the well-characterized pharmacological properties of its analog GW9662. An in vitro stability study showed that 40% of the compound remained intact in plasma and about 25% in whole blood after 30 min. Biodistribution studies in MDA-MB-435 human breast tumor-bearing nude mice were carried out at 5 min, 30 min, 2 h and 24 h post injection of the radiotracer. Although in vivo metabolite studies demonstrated rapid compound degradation, at least 10% of the parent compound was delivered to the tumor. We are currently exploring second generation analogs of these lead compounds for the development of radiolabeled antagonists of the PPARgamma receptor.
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PMID:Synthesis and evaluation of a bromine-76-labeled PPARgamma antagonist 2-bromo-5-nitro-N-phenylbenzamide. 1704 64

Previous studies have postulated the association between oxidative stress and Type 2 diabetes. Considering the long pre-diabetic period with IGR (impaired glucose regulation) and its high risk of developing diabetes, to test this hypothesis, we have investigated oxidative stress pathways and DNA damage in patients with IGR and newly diagnosed Type 2 diabetes. The study population consisted of 92 subjects with NGT (normal glucose tolerance), 78 patients with IGR and 113 patients with newly diagnosed diabetes. Plasma MDA (malondialdehyde) and TAC (total antioxidative capacity) status, erythrocyte GSH content and SOD (superoxide dismutase) activity were determined. A comet assay was employed to evaluate DNA damage. Compared with subjects with NGT, patients with IGR had reduced erythrocyte SOD activity. Patients with diabetes had a higher plasma MDA concentration, but a lower plasma TAC level and erythrocyte SOD activity, than the NGT group. Correlation analysis revealed a strong positive association between IR (insulin resistance) and MDA concentration, but negative correlations with TAC status and SOD activity. With respect to beta-cell function, a positive association with TAC status and an inverse correlation with GSH respectively, were observed. The comet assay revealed slight DNA damage in patients with IGR, which was increased in patients with diabetes. Significant correlations were observed between DNA damage and hyperglycaemia, IR and beta-cell dysfunction. In conclusion, the results of the present study suggest that hyperglycaemia in an IGR state caused the predominance of oxidative stress over antioxidative defence systems, leading to oxidative DNA damage, which possibly contributed to pancreatic beta-cell dysfunction, IR and more pronounced hyperglycaemia. This vicious circle finally induced the deterioration to diabetes.
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PMID:Oxidative stress, antioxidant status and DNA damage in patients with impaired glucose regulation and newly diagnosed Type 2 diabetes. 1720 2

In recent times there has been great demand for natural products that have possible preventive action against diabetes and its secondary complications. Keeping this in mind, this study was undertaken to investigate the influence of the flavonoid, quercetin, on oxidative stress markers and the antioxidant defence system of hepatic and neuronal tissues from galactose-induced hyperglycaemic rats. Weanling male Wistar rats were treated with 30% galactose in AIN 93 diet (group B, n=8) to induce hyperglycaemia. Control rats received normal Stock AIN 93 diet (group A, n=8). The third set of rats received group B diet with quercetin at 400 mg/100 g diet (group C, n=8). Glucose levels and body weights were measured on a weekly basis for four weeks to monitor the hyperglycaemia induced by galactose feeding. Parameters involved in the pathogenesis of galactose-induced hyperglycaemia, which included organosomatic index, protein content, antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), tryptophan fluorescence, content of protein carbonyls, prooxidant malonaldehyde (MDA) and glutathione (GSH) in hepatic and neuronal tissues were determined at the end of the fourth week. The study suggest that quercetin counters the pro-oxidant effects of galactose-induced hyperglycaemic stress, as there was a significant reversal of changes with respect to body weights, organosomatic index of hepatic and neuronal tissues, lipid peroxidation, protein carbonyl content, reduced glutathione and activities of antioxidant enzymes. In addition, treatment with quercetin appears to reduce the osmotic stress induced by hyperglycaemia, as assessed by polyol pathway enzyme aldose reductase. These results imply that inclusion of quercetin in the diet controls, to some extent, galactose-induced hyperglycaemia and its attendant complications.
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PMID:Effect of quercetin on galactose-induced hyperglycaemic oxidative stress in hepatic and neuronal tissues of Wistar rats. 1721 65

The objective of the present study was to investigate the possible neuroprotective effect of resveratrol against streptozotocin-induced hyperglycaemia in the rat brain and medulla spinalis. Thirty adult male Wistar rats were divided into three groups as follows: control group, streptozotocin-induced diabetic-untreated group, and streptozotocin-induced diabetic resveratrol-treated group. Diabetes was induced by a single injection of streptozotocin (STZ) (60 mg/kg body weight). Three days after streptozotocin injection, resveratrol (10 mg/kg) was injected intraperiteonally daily over 6 weeks to the rats in the treatment group. Six weeks later, seven rats from each group were killed and the brain stem and cervical spinal cord were removed. The hippocampus, cortex, cerebellum, brain stem and spinal cord were dissected for biochemical studies (lipid peroxidation measuring malondialdehyde [MDA], xanthine oxidase [XO], nitric oxide [NO] and glutathione). MDA, XO and NO levels in hippocampus, cortex, cerebellum, brain stem and spinal cord in the streptozotocin-induced diabetic-untreated group increased significantly. Treatment with resveratrol significantly reduced MDA, XO and NO production and increased glutathione levels when compared to the streptozotocin-induced diabetic-untreated group. This study demonstrates that resveratrol is a potent neuroprotective agent against diabetic oxidative damage.
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PMID:Central nervous system protection by resveratrol in streptozotocin-induced diabetic rats. 1725 34

Small low-density lipoprotein (LDL) particles and modifications to LDL such as glycation and oxidation have been linked to the pathogenesis of atherosclerosis in patients with diabetes. We investigated whether LDL particle size, or the levels of glycated LDL or malondialdehyde-modified LDL (MDA-LDL) are associated with carotid intima-media thickness (IMT) in patients with type 2 diabetes mellitus. One hundred seventy-two patients with type 2 diabetes mellitus were enrolled. Carotid IMT was measured by high-resolution ultrasound, and LDL particle size and serum glycated LDL and MDA-LDL levels were determined. The 3 variables were significantly correlated with one another. Univariate analyses defined statistically significant correlations of carotid IMT with LDL size, hemoglobin A(1c), glycated LDL, MDA-LDL, high-density lipoprotein (HDL) cholesterol, and age. The strongest association of IMT was with LDL size (r = -0.406, P < .0001), followed by that with HDL cholesterol (r = -0.225, P = .004). A stepwise multiple regression analysis revealed that LDL size and HDL cholesterol are independent predictors of carotid IMT. Neither glycated LDL nor MDA-LDL had a significant independent contribution to the severity of carotid IMT in the multivariate model. Low-density lipoprotein particle size, but not the glycated LDL or MDA-LDL level, was independently associated with carotid IMT in patients with type 2 diabetes mellitus regardless of antidiabetic and lipid-lowering medications. These results suggest that the measurement of LDL size may be more useful than quantification of modified LDLs for assessing atherosclerosis in patients with type 2 diabetes mellitus. Small LDL particles may be the most important predictor for the risk of cardiovascular disease in diabetic patients.
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PMID:Impact of low-density lipoprotein particle size on carotid intima-media thickness in patients with type 2 diabetes mellitus. 1744 34


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