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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Melatonin, which is synthesized in the pineal gland and other tissues, has a variety of physiological, immunological, and biochemical functions. It is a direct scavenger of free radicals and has indirect antioxidant effects due to its stimulation of the expression and activity of antioxidative enzymes such as glutathione peroxidase, superoxide dismutase and catalase, and NO synthase, in mammalian cells. Melatonin also reduces serum lipid levels in mammalian species, and helps to prevent oxidative stress in diabetic subjects. Long-term melatonin administration to diabetic rats reduced their hyperlipidemia and hyperinsulinemia, and restored their altered ratios of polyunsaturated fatty acid in serum and tissues. It was recently reported that melatonin enhanced insulin-receptor kinase and IRS-1 phosphorylation, suggesting the potential existence of signaling pathway cross-talk between melatonin and insulin. Because TNF-alpha has been shown to impair insulin action by suppressing insulin receptor-tyrosine kinase activity and its IRS-1 tyrosine phosphorylation in peripheral tissues such as skeletal muscle cells, it was speculated that melatonin might counteract TNF-alpha-associated insulin resistance in type 2 diabetes. This review will focus on the physiological and metabolic effects of melatonin and highlight its potential use for the treatment of cholesterol/lipid and carbohydrate disorders.
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PMID:Metabolic effects of melatonin on oxidative stress and diabetes mellitus. 1621 26

Oxidative stress has been defined as a loss of counterbalance between free radical or reactive oxygen species (ROS) production and antioxidant systems. It is involved in the pathogenesis of different chronic diseases. High levels of ROS production via different biochemical mechanisms accompany diseases like type 2 diabetes mellitus (DM) and end-stage renal disease (ESRD). Elevated oxidative status and reduced antioxidant defence systems in patients with DM and ESRD accelerate the prevalence of atherosclerosis and other chronic complications. Our aim was to reveal the effects of diabetes and haemodialysis (HD) separately and together on oxidative stress. In our study, we included 20 diabetic (DM) patients with no renal disease, 20 non-diabetic haemodialysis (HD), 20 diabetic haemodialysis (DHD) patients and 20 healthy volunteers. We have determined the levels of lipid peroxidation expressed as thiobarbituric acid-reactive substances (TBARS), oxidative protein damage as indicated by protein carbonyl (PCO) content and activities of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSHPx) in all patient groups and healthy subjects. We found enhanced oxidative stress in all patient groups due to an increase in lipid peroxidation (TBARS) and increased oxidative protein damage in terms of PCO content and reduced activities of SOD, CAT and GSH-Px. Oxidative stress was more profound in diabetic patients undergoing haemodialysis. We conclude that both diabetes and dialysis increase oxidative stress and their combined effect on oxidative stress is the highest in magnitude as observed in diabetic patients undergoing haemodialysis.
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PMID:Effect of haemodialysis on the oxidative stress and antioxidants in diabetes mellitus. 1625 35

Methanolic extract of Musa sapientum var. Paradisiaca (MSE, 100 mg/kg) was studied for its antiulcer and mucosal defensive factors in normal and non-insulin dependent diabetes mellitus (NIDDM) rats. NIDDM was induced by administering streptozotocin (STZ, 70 mg/kg, ip) to 5 days old rat pups. The animals showing blood glucose level >140mg/dL after 12 weeks of STZ administration were considered as NIDDM positive. Effects of MSE were compared with known ulcer protective drug, sucralfate (SFT, 500 mg/kg) and anti-diabetic drug glibenclamide (GLC, 0.6 mg/kg) when administered orally, once daily for 6 days against gastric ulcers (GU) induced by cold-restraint stress (CRS) and ethanol and subsequent changes in gastric mucosal glycoproteins, cell proliferation, free radicals (lipid peroxidation and nitric oxide) and anti-oxidants enzymes (super oxide dismutase and catalase) and glutathione (GSH) levels. MSE showed better ulcer protective effect in NIDDM rats compared with SFT and GLC in CRS-induced GU. NIDDM caused a significant decrease in gastric mucosal glycoprotein level without having any effect on cell proliferation. However, all the test drugs reversed the decrease in glycoprotein level in NIDDM rats, but cell proliferation was enhanced in case of MSE alone. Both CRS or NIDDM as such enhanced gastric mucosal LPO, NO and SOD, but decreased CAT levels while CRS plus NIDDM rats caused further increase in LPO and NO level without causing any further changes in SOD and CAT level. MSE pretreatment showed reversal in the levels of all the above parameters better than GLC. Ethanol caused a decrease in glutathione level which was further reduced in NIDDM-ethanol rats. MSE reversed the above changes significantly in both normal as well as in NIDDM rats, while GLC reversed it only in NIDDM rats. However, SFT was ineffective in reversing the changes induced by CRS or ethanol or when given in NIDDM-CRS or NIDDM-ethanol rats. The results indicated that the ulcer protective effect of MSE could be due to its predominant effect on mucosal glycoprotein, cell proliferation, free radicals and antioxidant systems.
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PMID:Effect of plantain banana on gastric ulceration in NIDDM rats: role of gastric mucosal glycoproteins, cell proliferation, antioxidants and free radicals. 1662 71

Succinic acid mono ethyl ester (EMS) was recently proposed as an insulinotropic tool in the treatment of non-insulin dependent diabetes mellitus. The aim of this study was to investigate the effect of EMS on oxidative stress in a streptozotocin (STZ)-nicotinamide induced type 2 diabetic model. The EMS was injected intraperitoneally at 8 micro mol/g body weight for 30 days. Plasma glucose, plasma insulin, thiobarbituricacid reactive substances (TBARS), hydroperoxides, superoxide dismutase (SOD), catalase (CAT), glutathione peroxide (Gpx), reduced glutathione (GSH), glutathione-S-transferase (GST), and vitamins C and E were assayed in liver and kidney. Treatment with EMS and metformin to diabetic rats resulted in a significant reduction in plasma glucose, TBARS, and hydroperoxides. In addition, the treated groups also showed a significant increase in the activities of plasma insulin, SOD, CAT, GPx, GST, GSH, vitamin C, and vitamin E in liver and kidney of STZ-nicotinamide-induced diabetic rats. Our result suggest that non glucidic nutrient, such as EMS as a potent antidiabetic, may optimalize antiperoxidative and antioxidants status by restoring the biochemical alterations found in STZ-nicotinamide-induced type 2 diabetes.
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PMID:Succinic acid monoethyl ester prevents oxidative stress in streptozotocin-nicotinamide-induced type2 diabetic rats. 1691 Mar 16

Our previous study showed that arteriolar tone is enhanced in Type 2 diabetes mellitus (T2-DM) due to an increased level of constrictor prostaglandins. We hypothesized that, in mice with T2-DM, hydrogen peroxide (H(2)O(2)) is involved in the increased synthesis of constrictor prostaglandins, hence enhanced basal tone in skeletal muscle arterioles. Isolated, pressurized gracilis muscle arterioles ( approximately 100 microm in diameter) of mice with T2-DM (C57BL/KsJ-db(-)/db(-)) exhibited greater basal tone to increases in intraluminal pressure (20-120 mmHg) than that of control vessels (at 80 mmHg, control: 25 +/- 5%; db/db: 34 +/- 4%, P < 0.05), which was reduced back to control level by catalase (db/db: 24 +/- 4%). Correspondingly, in carotid arteries of db/db mice, the level of dichlorofluorescein-detectable and catalase-sensitive H(2)O(2) was significantly greater. In control arterioles, exogenous H(2)O(2) (0.1-100 micromol/l) elicited dilations (maximum, 58 +/- 10%), whereas in arterioles of db/db mice H(2)O(2) caused constrictions (-28 +/- 8%), which were converted to dilations (maximum, 16 +/- 5%) by the thromboxane A(2)/prostaglandin H(2) (TP) receptor antagonist SQ-29548. In addition, arteriolar constrictions in response to the TP receptor agonist U-46619 were not different between the two groups of vessels. Endothelium denudation did not significantly affect basal tone and H(2)O(2)-induced arteriolar responses in either control or db/db mice. Also, in arterioles of db/db mice, but not in controls, 3-nitrotyrosine staining was detected in the endothelial layer of vessels. Thus we propose that, in mice with T2-DM, arteriolar production of H(2)O(2) is enhanced, which leads to increased synthesis of the constrictor prostaglandins thromboxane A(2)/prostaglandin H(2) in the smooth muscle cells, which enhance basal arteriolar tone. These alterations may contribute to disturbed regulation of skeletal muscle blood flow in Type 2 diabetes mellitus.
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PMID:H2O2 increases production of constrictor prostaglandins in smooth muscle leading to enhanced arteriolar tone in Type 2 diabetic mice. 1699 91

1. The aim of the present study was to reveal the possible involvement of thyroid hormones in the antihyperglycaemic and antiperoxidative effects of acarbose. 2. The effects of acarbose on changes in serum concentration of thyroid hormones, insulin and glucose in dexamethasone-induced type 2 diabetic mice were investigated. Simultaneously, changes in lipid peroxidation (LPO), reduced glutathione (GSH) content and the activity of associated endogenous anti-oxidant enzymes, such as superoxide dismuatase (SOD) and catalase (CAT), were investigated in renal and cardiac tissues, which are commonly affected in diabetes mellitus. 3. Although administration of dexamethasone (1.0 mg/kg, i.m., for 22 days) caused hyperglycaemia with a parallel increase in serum insulin and tissue LPO, it decreased thyroid hormone concentrations and the activity of SOD and CAT. 4. When dexamethasone-induced hyperglycaemic mice were treated with acarbose (10 mg/kg per day, p.o., for 15 days), levels of thyroid hormones were increased and most of the abnormalities, including serum insulin and glucose levels, tissue LPO, SOD and CAT activity and GSH content, were reversed. 5. These findings suggest the involvement of thyroid hormones in the mode of action of acarbose in amelioration of type 2 diabetes mellitus.
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PMID:Antihyperglycaemic and antiperoxidative roles of acarbose in type 2 diabetes mellitus are possibly mediated through changes in thyroid function. 1704 22

Diabetes mellitus is characterized by fasting hyperglycemia, with both type 1 and type 2 diabetes. Persons are also known to be prone to develop complications related to elevated blood glucose concentrations, including atherosclerosis, retinal damage, cataract, and neuropathy. Hyperglycemia may also result in increased production of the reactive oxygen species within numerous biochemical pathways that have the potential to initiate changes in endothelial function. This article demonstrates the presence of lipid peroxidation products in the red cell membranes of type 2 diabetic patients compared to the normal subjects. These membranes are more susceptible to exogenous oxidative stress than those of normal healthy individuals. Significantly higher activities of antioxidant enzymes, namely, serum peroxidase, superoxide dismutase (SOD), and catalase (CAT) were found in type 2 diabetic patients as compared to control. This study led us to conclude that elevated levels of glucose induce oxidative stress that is ultimately reflected by the increased malondialdehyde (MDA) levels in erythrocyte ghost membranes of diabetic patients. Hyperglycemia also induced an increase in antioxidant enzymes and a relationship seems to exist between diabetic complications and elevated levels of these enzymes. It is suggested that these antioxidant enzymes may be considered as markers for vascular injury.
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PMID:Lipid peroxidation and serum antioxidant enzymes in patients with type 2 diabetes mellitus. 1715 23

Eucommia ulmoides Oliver (Du-zhong) leaf extract was investigated for its antioxidant effects in type 2 diabetic animals, C57BL/KsJ-db/db mice. Du-zhong extract equivalent to 1% dried whole Du-zhong leaf (0.187 g of extract/100 g of diet) was added to the experimental diets for 6 weeks. The Du-zhong extract supplement significantly lowered blood glucose concentrations and elevated plasma paraoxonase activity compared with the control group. The activities of erythrocyte superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were significantly higher in the Du-zhong group compared with the control group, while glutathione reductase (GR) activity was not different between groups. The activities of SOD, GSH-Px, and GR in liver and kidney were not affected by Du-zhong extract supplementation, whereas the CAT activity was significantly higher in the Du-zhong group than in the control group. Du-zhong extract supplementation resulted in lower levels of hydrogen peroxide and lipid peroxide in erythrocytes, liver, and kidney. These results suggest that the antioxidant activity of Du-zhong extract is potentially beneficial for the prevention and management of complications of type 2 diabetes.
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PMID:Eucommia ulmoides Oliver leaf extract increases endogenous antioxidant activity in type 2 diabetic mice. 1720 32

Thiazolidinediones (TZDs) are a new class of antidiabetic drugs, having an insulin sensitizing effect in patients with type 2 diabetes. The contribution of oxidative stress from the standpoint of lipid and protein damage, alteration in endogenous antioxidant enzymes and effects of newly synthesized compounds, 5-[4-2-(6,7-Dimethyl-1,2,3,4-tetrahydro-2-oxo-4-quinoxalinyl)ethoxy]phenyl]methylene]thiazolid- ine-2,4-dione, (C(1)) in normal/alloxan-induced diabetic rats form the focus area of this study. Its effect was compared to two well-known TZDs, namely pioglitazone and rosiglitazone. It has been concluded from results that after thirty days of administration of C(1), Pg and Rg in alloxan-induced diabetic animal groups, the blood glucose level decreased, more remarkably in C(1) treated group. Also oxidative damage has been studied by estimating hepatic superoxide dismutase (SOD) activity, which was found to be increased (p<0.001 vs. control). An inverse change in SOD values between hepatic and pancreatic/kidney tissues were observed. Treatment with the test compounds lowered the activity of SOD in liver while increased its activity in kidney and pancreas. Similar normalizing effect of C(1) on liver, pancreatic and renal catalase (CAT)/ glutathione peroxidase (GPx) activities were pronounced in diabetic rats (p<0.001 vs. diabetic rats). Decreased reduced glutathione (GSH) content, found in diabetic animals, was significantly elevated to normal levels by C(1) treatment. The treatment with C(1) also decreased the levels of nitric oxide and increased the activities of glutathione-s-transferase and glutathione reductase, as compared to diabetic animals. Evidence of oxidative damage to lipids and proteins was shown through the quantification of protein carbonyl (in tissues) and malondialdehyde levels (both serum and tissues). It was observed that the protein/lipid damage in diabetic rats was improved by treatment with C(1). Total antioxidant activity (TAA) was found to be enhanced in C(1) treated rats (p>0.05 vs. group3, p<0.001 vs. group2, p<0.001 vs. group 4). These results suggest that the newly synthesized TZD derivative (C(1)) has a potential to act as antihyperglycemic and antioxidant agent. In addition, for all parameters checked, it has better efficacy than rosiglitazone and is as effective as pioglitazone.
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PMID:Antihyperglycemic effect of a new thiazolidinedione analogue and its role in ameliorating oxidative stress in alloxan-induced diabetic rats. 1723 17

Catalase is a central antioxidant enzyme constituting the primary defense against oxidative stress. In this study, we investigated whether the functional -262C/T polymorphism in the promoter of catalase gene is associated with the presence of diabetic retinopathy (DR), diabetic nephropathy (DN) and ischemic heart disease (IHD) in 520 Caucasian-Brazilians with type 2 diabetes. The -262C/T polymorphism was also examined in 100 Caucasian blood donors. Patients underwent a clinical and laboratory evaluation consisting of a questionnaire, physical examination, assessment of diabetic complications and laboratory tests. Genotype analysis was performed using the polymerase chain reaction followed by digestion with restriction enzyme. The genotype and allele frequencies of the -262C/T polymorphism in patients with type 2 diabetes were very similar to those of blood donors (T allele frequency=0.20 and 0.18, respectively). Likewise, there were no differences in either genotype or allele frequencies between type 2 diabetic patients with or without DR, DN or IHD. Thus, our results do not support the hypothesis that the -262C/T polymorphism is related to the development of DR, DN or IHD in patients with type 2 diabetes. Further studies are necessary to elucidate the role of catalase gene polymorphisms in the pathogenesis of diabetic complications.
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PMID:The catalase -262C/T promoter polymorphism and diabetic complications in Caucasians with type 2 diabetes. 1726 7


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