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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have compared the concentrations of intracellular glutathione (GSH), glutathione-dependent antioxidative enzymes, the cell death rate and immunophenotype profile of peripheral blood mononuclear cells (PBMC) from healthy donors and from patients with insulin-dependent type II (NIDDM) diabetes mellitus. The IDDM and NIDDM patients had above-normal absolute lymphocyte counts, whereas the percentages of CD3, CD4 adn CD8 T lymphocytes were significantly reduced. In contrast, the absolute number and percentage of B lymphocytes was higher in diabetic patients than in healthy donors. The low intracellular reduced glutathione(GSH) and the unbalanced profile of key enzymes involved in GSH metabolism, gamma-glutamyltransferase (gamma-GT) and glutathione-S-transferase (GST), account for the increased oxidative status of PBMC from diabetic patients. The plasma membranes of PBMC for diabetic patients were less permeable to propidium iodide than those of PBMC from healthy donors, indicating that the apoptotic cell death rate was lower in the cells from diabetic patients. These differences are potentially useful markers of pathogenic metabolic changes which occur during clinical diabetes and if they are confirmed could be use dot identify the onset of diabetes.
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PMID:Apoptosis and oxidative status in peripheral blood mononuclear cells of diabetic patients. 1469 96

This study evaluated several parameters related to mitochondrial function and oxidative stress in streptozotocin (STZ)-treated rats, a model of type 1 diabetes. For this purpose, the respiratory indexes (RCR and ADP/O ratio), mitochondrial transmembrane potential (DeltaPsim), repolarization lag phase, repolarization level, mitochondrial enzymatic activities, ATP and malondialdehyde (MDA) levels, reduced glutathione (GSH), vitamin E and cardiolipin contents were determined in rat brain mitochondria isolated after 4 and 9 weeks after STZ treatment. Brain mitochondria isolated from citrate (vehicle)-treated Wistar rats were used as control. We observed that STZ-induced diabetes did not substantially affect brain mitochondrial function. Instead, 4-week diabetic rats presented higher mitochondrial respiratory chain enzymatic activities, especially succinate-cytochrome C reductase activity, compared to 4-week control rats. In 9-week diabetic rats, only a significant decrease in cardiolipin content was observed; however, a significant increase in mitochondrial GSH content occurred. All other parameters analysed remained statistically unchanged. From these results, we conclude that STZ-induced diabetes did not promote brain mitochondrial dysfunction, suggesting that oxidative stress associated with type 1 diabetes is not directly related to mitochondrial dysfunction, but probably is related to extramitochondrial factor(s).
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PMID:Effect of streptozotocin-induced diabetes on rat brain mitochondria. 1496 73

Diabetic cardiomyopathy is a common complication leading to heightened risk of heart failure and death. In the present report, we performed proteomic analysis on total cardiac proteins from the OVE26 mouse model of type 1 diabetes to identify protein changes that may contribute to diabetic cardiomyopathy. This analysis revealed that a surprising high proportion (12 of 20) of the altered proteins that could be identified by mass spectrometry were of mitochondrial origin. All but one of these proteins were upregulated by diabetes. Quantitative RT-PCR, performed for two of these proteins, indicated that part of the upregulation was attributed to increased messenger RNA levels. Morphological study of diabetic hearts showed significantly increased mitochondrial area and number as well as focal regions with severe damage to mitochondria. Diabetic mitochondria also showed reduced respiratory control ratio (9.63 +/- 0.20 vs. 6.13 +/- 0.41, P < 0.0001), apparently due to reduced state 3 rate, and diminished GSH level (5.5 +/- 0.9 vs. 8.2 +/- 2.5 micromol/mg protein, P < 0.05), indicating impaired mitochondrial function and increased oxidative stress. Further examination revealed increased mitochondrial DNA (1.03 +/- 0.18 vs. 0.69 +/- 0.13 relative copy number, P < 0.001) and a tendency to higher protein yield in OVE26 cardiac mitochondria, as well as increased mRNA level for mitochondrial transcription factor A and two mitochondrial encoded proteins. Taken together, these results show that mitochondria are a primary target in the diabetic heart, probably due to oxidative stress, and that this damage coincides with and may stimulate mitochondrial biogenesis.
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PMID:Cardiac mitochondrial damage and biogenesis in a chronic model of type 1 diabetes. 1528 Jan 50

Diabetic pregnancy is often complicated by a number of pathological conditions among which is increased oxidative stress. This study was conducted to investigate the parameters of oxidative stress in 90 patients divided into the three groups: pregnant women with Type 1 diabetes mellitus, healthy pregnant women and non-pregnant women. In pregnancy groups all parameters were followed in 1st, 2nd and 3rd trimester. Diabetic control was monitored by fasting blood glucose and glycosylated hemoglobin (HbA(1c)) and these values, as well as measured biochemical parameters (urea, creatinine, total cholesterol and uric acid), were appropriate throughout the study. The concentration of TBARS, as a measure of lipid peroxidation, and activity of antioxidant enzymes superoxide dismutase (Cu, Zn-SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were investigated in hemolysate of erythrocytes. TBARS concentration increased significantly in pregnant women when compared with control group (non-pregnant women), as well as in pregnant diabetics compared with healthy pregnant women. The SOD activity was gradually increased in the group of normal pregnant women vs. non-pregnant group, but decreased significantly in the group of diabetic pregnant women. Catalase activity was significantly increased only in 3rd trimester diabetic pregnant women. Increased lipid peroxidation and reduced antioxidant status, despite good diabetic control, show that pregnant women are exposed to oxidative stress to a greater degree than controls.
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PMID:Oxidative stress in diabetic pregnancy: SOD, CAT and GSH-Px activity and lipid peroxidation products. 1562 58

In the present study, we investigated the antioxidant status in diabetes mellitus, related or not to alcohol consumption. A total of 38 type 1, 48 type 2 and 42 alcohol-related diabetic patients were selected. Total antioxidant status was assessed through the oxygen radical absorbance capacity of the plasma and the determination of enzymatic and non-enzymatic antioxidant molecules. Serum triglycerides, total cholesterol and HDL-cholesterol concentrations were determined and the lipid peroxydation was evaluated by measuring thiobarbituric acid reactive substances (TBARS) assay. Plasma total antioxidant capacity was more decreased in alcohol-related diabetes than that in type 1 and type 2 diabetes, regardless of the complications (retinopathy and renal failure). Plasma vitamin E concentrations were significantly decreased whereas those of vitamin C increased in all of the diabetic patients compared to the controls, irrespective to the complications. In addition, superoxide dismutase and glutathione peroxidase activities were reduced in all the patients (type 1, type 2 and alcohol-related), irrespective to the complications. Glutathione reductase activity was diminished in type 1 and alcohol-related, but not in type 2, diabetic patients. Glutathione (GSH) concentrations significantly decreased in all diabetic patients with a significant decrease in alcohol-related diabetic patients. Excessive alcohol consumption appears as an oxidative aggravating factor in diabetes mellitus. Besides, alcohol-related diabetes highly resembles to type 1 diabetes as far as the antioxidant parameters are concerned.
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PMID:Antioxidant status in alcohol-related diabetes mellitus in Beninese subjects. 1637 21

In this study, malondialdehyde (MDA) level as an index of erythrocyte susceptibility to oxidative stress and antioxidant defense system (glutathione level (GSH), glutathione peroxidase enzyme activity (GPx) in erythrocytes and ferric reducing ability of plasma (FRAP) as the total plasma antioxidant capacity were measured in 35 patients with type 1 diabetes and 28 age and sex-matched normal subjects. MDA level was significantly elevated in diabetic patients (650.9+/-144.3 nmol/g versus 476.5+/-138.5 nmol/g Hb, P<0.001). The level of MDA was positively correlated with duration of diabetes (r= 0.29, P<0.05) and HbA(1C) (r= 0.39, P<0.05) and negatively with FRAP (r= -0.3, P<0.05). The level of GSH and FRAP were lower in patients than controls (7.05+/-1.6 micromol/g versus 8.24+/-0.9 micromol/g Hb, and 389.05+/-82.3 micromol/l versus 520.4+/-124.1 micromol/l, respectively, P<0.001). GPx activity was not significantly different between the two groups. GSH and FRAP were negatively correlated with HbA(1C) (r= -0.334, P<0.01 and r= -0.5, P<0.01, respectively). In conclusion, there seems to be an increased susceptibility to oxidative stress and decreased antioxidant defense in patients with type 1 diabetes, which may be due to poor glycemic control.
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PMID:Erythrocyte susceptibility to oxidative stress and antioxidant status in patients with type 1 diabetes. 1736 68

This study aimed to investigate the interrelationship of plasma lipid profile, lipid peroxidation, and erythrocyte antioxidative defense in patients with insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus. Plasma levels of total cholesterol, triglycerides, and lipid peroxides and the activities of copper, zinc superoxide dismutase (CuZnSOD), catalase, glutathione peroxidase (GSH-Px), as well as the amount of glutathione in erythrocytes, were determined in IDDM, NIDDM, and nondiabetic control subjects. Additionally, morphology of erythrocytes in all subjects was examined. Plasma levels of total cholesterol and triglycerides were significantly increased in NIDDM compared with controls. Also, the lipid peroxide level was higher in NIDDM than in either control or IDDM subjects. CuZnSOD activity in erythrocytes was elevated in NIDDM patients compared with the control. In NIDDM patients, more extensive erythrocyte spherocytosis and echinocytosis compared with both control and IDDM subjects were observed. In contrast with the IDDM group, the observed abnormality in lipid metabolism in NIDDM patients is closely associated with increased lipid peroxidation, changes in antioxidative defense, and erythrocyte morphology.
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PMID:Interrelationship of antioxidative status, lipid peroxidation, and lipid profile in insulin-dependent and non-insulin-dependent diabetic patients. 1806

Subjects with type 1 diabetes mellitus (T1DM) eventually develop insulin resistance and other features of T2DM such as cardiovascular disorders. The exact mechanism has been not been completely understood. In this study, we tested the hypothesis that excessive or inappropriate exposure to insulin is a primary mediator of insulin resistance in T1DM. We found that continuous exposure of mice with non-obese diabetes to insulin detemir, which is similar to some current conventional treatment of human T1DM, induced severe insulin resistance, whereas untreated hyperglycemia for the same amount of time (2 weeks) did not cause obvious insulin resistance. Insulin resistance was accompanied by decreased mitochondrial production as evaluated by mitochondrial DNA and levels of transcripts and proteins of mitochondrion-associated genes, increased ectopic fat accumulation in liver and skeletal muscle (gastrocnemius) evaluated by measurements of triglyceride content, and elevated oxidative stress detected by the GSH/GSSG ratio. Prolonged exposure of cultured hepatocytes to insulin induced significant insulin resistance, whereas the same length of exposure to a high level of glucose (33 mm) did not cause obvious insulin resistance. Furthermore, our results showed that prolonged exposure to insulin caused oxidative stress, and blockade of mitochondrion-derived oxidative stress by overexpression of manganese-superoxide dismutase prevented insulin resistance induced by the prolonged exposure to insulin. Together, our results show that excessive exposure to insulin is a primary inducer of insulin resistance in T1DM in mice.
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PMID:Insulin is a stronger inducer of insulin resistance than hyperglycemia in mice with type 1 diabetes mellitus (T1DM). 1965 21

Our aim was to investigate the hypoglycaemic and antioxidant effects of the Helichrysum plicatum ssp. plicatum (HPsP) plant extract in the streptozotocin-induced type 1 diabetes rat model during pregnancy. Five groups (n = 8, each) were formed: (1) diabetic non-mated control, (2) non-diabetic mated control, (3) diabetic mated control, (4) diabetic non-mated treatment and (5) diabetic mated treatment. The HPsP extract was administered orally for 15 days (250 mg/kg body weight), beginning 3 days before mating. The extract led to decreased blood glucose, increased serum insulin, and decreased serum triglycerides in pregnant and non-pregnant diabetic animals. Liver thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) measurements in extract-treated diabetics were similar to non-diabetic pregnant controls, indicating probable reversal of increased lipid peroxidation in the liver. The mean pup number tended to increase (p = 0.06) with extract administration. In conclusion, the beneficial effects we encountered with the periconception use of the studied herbal extract warrant further investigation.
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PMID:Improved metabolic control and hepatic oxidative biomarkers with the periconception use of Helichrysum plicatum ssp. plicatum. 2014 69

Diabetic mellitus, a chronic metabolic disorder, is one of the most important health problems in the world, especially in developing countries. Our earlier investigations reported the beneficial action of arjunolic acid (AA) against streptozotocin-mediated type 1 hyperglycemia. We have demonstrated that AA possesses protective roles against drug- and chemical- (environmental toxins) induced hepatotoxicity. Liver is the main organ of detoxification. The purpose of this study was to explore whether AA plays any protective role against hyperglycemic hepatic dysfunctions and, if so, what molecular pathways it utilizes for the mechanism of its protective action. In experimental rats, type 1 hyperglycemia was induced by streptozotocin. AA was administered orally at a dose of 20mg/kg body wt both before and after diabetic induction. An insulin-treated group was included in the study as a positive control for type 1 diabetes. Hyperglycemia caused a loss in body weight, reduction in serum insulin level, and increased formation of HbA(1C) as well as advanced glycation end products (AGEs). Elevated levels of serum ALT and ALP, increased production of ROS and RNS, increased lipid peroxidation, increased 8-OHdG/2-dG ratio, and decreased GSH content and cellular antioxidant defense established the hyperglycemic liver dysfunction. Activation of iNOS, IkappaBalpha/NF-kappaB, and MAPK pathways as well as signals from mitochondria were found to be involved in initiating apoptotic cell death. Hyperglycemia caused overexpression of PARP, reduction in intracellular NAD as well as ATP level, and increased DNA fragmentation in the liver tissue of the diabetic animals. Results of immunofluorescence (using anti-caspase-3 and anti-Apaf-1 antibodies), DAPI/PI staining, and DNA ladder formation and information obtained from FACS analysis confirmed the apoptotic cell death in diabetic liver tissue. Histological studies also support the experimental findings. AA treatment prevented or ameliorated the diabetic liver complications and apoptotic cell death. The effectiveness of AA in preventing the formation of ROS, RNS, HbA(1C), AGEs, and oxidative stress signaling cascades and protecting against PARP-mediated DNA fragmentation can speak about its potential uses for diabetic patients.
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PMID:Contribution of type 1 diabetes to rat liver dysfunction and cellular damage via activation of NOS, PARP, IkappaBalpha/NF-kappaB, MAPKs, and mitochondria-dependent pathways: Prophylactic role of arjunolic acid. 2018 23


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