Mineralocorticoid receptor blockade prevents vascular remodelling in a rodent model of type 2 diabetes mellitus

2015 ◽  
Vol 129 (7) ◽  
pp. 533-545 ◽  
Author(s):  
Marcondes Alves B. Silva ◽  
Stefany Bruno A. Cau ◽  
Rheure Alves M. Lopes ◽  
Carla P. Manzato ◽  
Karla B. Neves ◽  
...  

Spironolactone prevents vascular remodelling in diabetes by reducing oxidative stress, hypertrophy and cell proliferation in the vascular wall. Thus, MR (mineralocorticoid receptor) antagonism is effective in the prevention of hyperglycaemia-associated vascular injury, reducing organ damage and increasing survival of diabetic patients.

2008 ◽  
Vol 27 (3) ◽  
pp. 376-382 ◽  
Author(s):  
Tatjana Cvetković ◽  
Predrag Vlahović ◽  
Vidosava đorđević ◽  
Lilika Zvezdanović ◽  
Dušica Pavlović ◽  
...  

The Significance of Urinary Markers in the Evaluation of Diabetic Nephropathy Oxidative stress is considered to be a unifying link between diabetes mellitus (DM) and its complications, including nephropathy (DN). The aim of this study was to determine the parameters of oxidative injury of lipids and proteins as well as the activity of ectoenzymes in the urine of DN patients. The study included 40 individuals: 10 patients with type 2 diabetes mellitus and microalbuminuria (DMT2-MIA), 10 type 2 diabetic patients with macroalbuminuria (DMT2-MAA), 10 patients with type 1 diabetes and microalbuminuria (DMT1-MIA) and 10 age- and sex-matched healthy subjects (control). In the urine we determined TBA reactive substances (TBARS), reactive carbonyl groups (RCG), and the activity of ectoenzymes N-acetyl-β-d-glucosaminidase (NAG), plasma cell differentiation antigen (PC-1), aminopeptidase N (APN) and dipeptidyl peptidase IV (DPP IV). A higher concentration of TBARS in the urine was found in DMT2-MIA and DMT1-MIA, compared to the control group (p<0.001 and P<0.05). The urine concentration of RCD shows similar results with a significant elevation in the groups with DMT2-MAA and DMT1-MIA, compared to the DMT2-MIA (p<0.001) and control group (p<0.001). Activities of NAG, APN and DPPIV were significantly higher in the urine of DMT2-MAA, compared to the control (p<0.01). The activity of PC-1 was slightly increased in that group, but not significantly. In conclusion, the level of oxidative stress markers and activities of brush border ectoenzymes in the urine may be a useful non-invasive and easily repeatable test in DN.


Author(s):  
Gangaram Bhadarge ◽  
Pratibha Dawande ◽  
Nandkishor Bankar ◽  
Raunak Kotecha

Introduction: Zn supplementation improved glutathione peroxidase enzyme activity and decreased malondialdehyde and nitric oxide levels in diabetic rats, revealing Zn's defensive effect against oxidative stress in type 2 diabetes. The investigators have discovered that consuming Zn increased liver function and protected pancreatic tissue from damage caused by diabetes. Since Zn also prevents chronic hyperglycemia, it helps to minimize oxidative stress caused by type 2 diabetes. Diabetes mellitus (DM) is a global health problem that affects more than 3 million people worldwide (16% of population). Chronic hyperglycemia causes oxidative stress in diabetic patients by the development of free radicals (oxidants) and lowering the antioxidant protection mechanism. Aim: Glycaemic Regulation with Zinc Combination in Type 2 Diabetes Mellitus. Materials and Methods: Faculty of Medicine and Diabetic Opd, Datta Meghe Mediсаl Соllege and Shаlinitаi Meghe Hоsрitаl аnd Reseаrсh Сenter, Nаgрur in соllаbоrаtion with Dаttа Meghe Institute оf Mediсаl Sсienсes Deemed to be University, Sаwаngi, Wаrdhа, Mаhаrаshtrа. Results: The mean Zn level was 12.213±2.342in all participants and 9.121±1.782 in the control group, whereas it was significantly low (9.121±1.782) in the diabetic group, and there was statistically significant difference in Zn levels between the controls and the diabetic group (P < 0.001).FBS, HbA1C, serum Zinc mean effects between control and patients showed statistically significant differences in type 2 diabetes mellitus (P <0.0001). Conclusion: Our findings show that people with diabetes have lower levels of Zn than healthy people. The cause and effect of the association between very low levels of Zn and the progression of diabetes, or diabetes that causes Zn deficiency, is still unknown. Low levels of Zn are associated with poor glycemic control, and poor glycemic control is a good indication of Zn deficiency, as there was a negative association between serum Zn and FBS and HBA1C. If diabetic patients have low glycemic regulation, a long history of diabetes, obesity, or are over the age of 50, we look to assess their levels in Zn so that Zn alternative treatment can begin to release oxidative stress in this high-risk group.


2016 ◽  
Vol 17 (1) ◽  
pp. 35-41
Author(s):  
Nevena Gajovic ◽  
Ivan Jovanovic ◽  
Aleksandar Ilic ◽  
Nevena Jeremic ◽  
Vladimir Jakovljevic ◽  
...  

Abstract Diabetes mellitus is chronic disorder characterized by hyperglycaemia. Hyperglycaemia induces mitochondrial dysfunction, enhances oxidative stress and thus promotes reactive oxygen species (ROS) production. Earlier studies suggested that reactive oxygen species (ROS) are involved in the pathogenesis of many diseases. Previous studies have revealed that hyperglycaemia changes the functional phenotype of monocytes, macrophages, neutrophils, NK cells and CD8+ T cells. The aim of this study was to investigate whether diabetes affects the functional phenotype of NKT cells. Diabetes mellitus was induced in BALB/c mice by intraperitoneal injection of streptozotocin at a single dose of 170 mg/kg body weight. The number and functional phenotype of splenic NKT cells was assessed by fl ow cytometry, 28 days after diabetes induction. The diabetic condition facilitated the production of antioxidant enzymes, including catalase (p<0.05) and superoxide dismutase. Hyperglycaemia enhanced oxidative stress and thus decreased the number of splenic NKT cells but did not change the percentage of splenic CD3+CD49+ NKT cells that express the activatory receptor NKP46 or produce IFN-γ. However, hyperglycaemia increased the frequency of splenic NKT cells that express KLRG-1 and produce TGF-β, IL-4, and IL-5, and it decreased the frequency of IL-17+ NKT cells. Our study indicates that diabetes mellitus induces oxidative stress and switches the functional phenotype of NKT cells towards type 2 (IL-4 and IL-5 producing NKTs) and regulatory (TGF-β Thproducing NKTs) phenotypes. These findings are correlated with the clinical observation in humans that diabetic patients are more prone to infections and tumours.


2016 ◽  
Vol 94 (3) ◽  
pp. 221-224
Author(s):  
Irina A. Romanenko ◽  
T. S. Polyatykina ◽  
N. V. Mavrycheva ◽  
N. V. Budnikova ◽  
V. B. Grinshtein

We studied lipid and carbohydrate metabolism, markers of oxidative stress (plasma malonic dialdehyde and dienoic conjugates) and vascular wall damage (CRP, microalbuminuria, blood desquamated endotheliocytes) before and after 12 week treatment of obese pre-diabetic patients. The study showed positive dynamics of the above metabolic parameters with normalization of carbohydrate metabolism in 60% of the patients and angioprotective effect ofprescribed therapy. The proposed treatment can be used to prevent diabetes mellitus.


Author(s):  
P. Divya ◽  
R. Inmozhi Sivakamasundari ◽  
T. K. Jithesh ◽  
K. Santha ◽  
K. Shifa ◽  
...  

Background: Diabetes mellitus is rising all over the world due to population growth, aging, urbanisation, and the increase of obesity due to physical inactivity, characterized by persistent high blood glucose levels associated with aberrations in lipid, carbohydrate, and protein metabolisms leading to water and electrolyte imbalance. Cardiovascular diseases are the leading causes of mortality in diabetic patients. Mechanisms such as oxidative stress, lipid metabolism imbalance, as well as myocardial cell apoptosis are key factors to facilitate the progression of Diabetic cardiomyopathy. Aim: The aim of this study was to assess FGF-21 levels and their association with lipid profile parameters and oxidative stress in patients with type 2 diabetes mellitus. Methods: A patient based cross-sectional study was conducted among the subjects with history of type 2 DM for the past 10 years. Results: Variations in FBS, T.C, TG, LDL, HDL, VLDL, FGF-21, MDA and AOPP levels among cases and controls were depicted in Table 2. There was an increase in all these parameters in cases compared to controls whereas HDL showed a decrease among cases. Conclusion: Our study concluded that there is a significant correlation between fibroblast growth factor 21 (FGF-21), oxidative stress, and abnormal lipid profile in type 2 diabetic patients. We would recommend further studies to explore the role of FGF21 as an important marker in predicting cardiovascular risk in diabetic patients.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Natalia Brailova ◽  
Ekaterina Dudinskaya ◽  
Valentina Pykhtina ◽  
Ekaterina Plochova ◽  
Irina Strazhesko ◽  
...  

Introduction: Type 2 diabetes mellitus (T2DM) contribute to vascular aging. The telomere length (TL) and telomerase activity (TA) are considered as biomarkers of cellular aging. TL and TA are insufficiently studied in diabetic patients. Hypothesis: Telomere biology is associated with vascular aging in diabetic patients. Methods: The study group included 50 patients with T2DM (mean age 58.4±7.83 years) and 139 healthy patients (mean age 57.45±8.14 years). All subjects were measured for TL and TA by quantitative polymerase chain reaction; oxidative stress marked by malondialdehyde (MDA); inflammation marked by C-reactive protein (CRP); arterial stiffness evaluated by pulse wave velocity (PWV); carotid intima-media thickness (IMT), plaque presence (PP) and endothelial dysfunction evaluated by flow-mediated endothelium-dependent vasodilation (FMV). Results: All patients were divided into 4 groups by the median of TL (9.75): «short» telomeres (T2DM+ (n=15) and T2DM- (n=63) and «long» telomeres (T2DM+ (n=35) and T2DM- (n=76)). Patients with T2DM and «long» TL had the state of vessels, oxidative stress, inflammation, TA as similar as in healthy people: PWV 11.54±3.57 (T2DM+) vs 10.98±1.83 m/s (T2DM-) ((=0.58), IMT 0.83±0.13 vs 0.76±0.16 mm (=0.13), PP 1.36±0.33 vs 1.23±0.20 (=0.79); MDA 2.81±0.78 vs 3.24±0.78 mkmol/l (=0.08); CRP 3.59±0.58 vs 3.66±0.50 mg/l (=0.93); TA 0.51±0.09 vs 0.60±0.05 (p=0.36). FMV was higher in diabetic patients: 11.87±3.36 vs 10.18±2.79 % (=0.049). In contrast patients with «short» TL and T2DM had more pronounced vascular aging, inflammation and lower TA than healthy people: PWV 13.48±3.24 vs 11.59±2.03 m/s (=0.003), IMT 0.95±0.17 vs 0.78±0.14 mm (<0.001), PP 2.23±0.27 vs 1.38±0.17 (=0.006), FMV 8.51±3.20 vs 11.04±3.01% (=0.0002; CRP 7.39±1.47 vs 4.03±0.62 mg/l (=0.046); TA 0.47±0.08 vs 0.62±0.07 (p=0.06). Conclusion: In patients with short telomeres and T2DM signs of vascular aging, chronic inflammation and cellular aging were more pronounced than in healthy people. In contrast, in patients with long telomeres and T2DM vascular changes, oxidative stress, chronic inflammation and TA were as similar as in healthy people. Perhaps long telomeres protect patients with T2DM from accelerated vascular aging.


2016 ◽  
Vol 62 (1) ◽  
pp. 16-24 ◽  
Author(s):  
Natalia Vasil'evna Brailova ◽  
Ekaterina Nail'evna Dudinskaya ◽  
Olga Nikolaevna Tkacheva ◽  
Marina Vladimirovna Shestakova ◽  
Irina Dmitrievna Strazhesko ◽  
...  

Aim.To study the association of chronic inflammation, oxidative stress with telomere biology in people with type 2 diabetes mellitus (T2DM).Material and Methods.A total 50 patients with T2D and without cardiovascular disease (CVD) and 139 people from control group were included in the study. All subjects were measured for carbohydrate metabolism; oxidative stress (malondialdehyde (MDA)); inflammation (C-reactive protein — CRP, fibrinogen, interleukin-6); lymphocyte telomere length, telomerase activity.Results.In diabetic patients telomeres were shorter than in controls (9.59±0.54 and 9.76±0.47; p=0.031), telomerase activity was lower (0.47±0.40 and 0.62±0.36; p=0.039), inflammation (CRP, elevated fibrinogen) was higher. All patients were divided by telomere length. In T2DM group CRP was higher in patients with «short» telomeres (7.39±1.47 and 3.59±0.58 mg/L; p=0.02). There were no significant differences in the level of chronic inflammation and oxidative stress in ‘long’ telomeres group: CRP 3.59±0.58 and 3.66±0.50 mg/L (p=0.93), MDA 2.81±0.78 and 3.24±0.78 mmol/l (p=0.08). Diabetic patients in «short» telomeres group had greater chronic inflammation: CRP 7.39±1.47 and 4.03±0.62 mg/L (p=0.046), increased fibrinogen, 0.371 and 0.159 (p=0.022). All patients were divided by telomerase activity. Severity of chronic inflammation was greatest in T2DM and the «low» activity of telomerase. There were relationship between telomere length and CRP in T2DM patients (r=–0.40; p=0.004).Conclusions. Chronic inflammation and cell aging were more pronounced in patients with T2DM. However, despite diabetes, signs of chronic inflammation were minimal in patients with «long» telomeres compared to healthy people. Perhaps long telomeres protect diabetic patients from the damaging effect of chronic inflammation.


2010 ◽  
Vol 56 (5) ◽  
pp. 545-551
Author(s):  
S.I. Rizvi ◽  
N. Srivastava

Erythrocyte oxidative stress has been implicated in the pathogenesis of diabetes mellitus, and the deficiency of antioxidant defense by the glutathione (GSH) pathway is thought to be one of the factors responsible for development of complications in diabetes. Erythrocytes require L-cysteine for the synthesis of GSH and the rate of synthesis is determined only by L-cysteine availability. In the present study we have found that the L-cysteine influx in erythrocytes from type 2 diabetic patients was significantly lower compared to age-matched controls. The decreased influx may be one of the factors leading to low GSH concentration observed in type 2 diabetes. Since L-cysteine is the limiting amino acid in GSH synthesis, any strategy aimed to increase L-cysteine influx in erythrocytes may be beneficial for type 2 diabetic patients.


2019 ◽  
Vol 6 (3) ◽  
pp. 673
Author(s):  
Heena Singla ◽  
Gitanjali Goyal ◽  
Cheenu Garg ◽  
Kajal Bhalla

Background: Diabetes mellitus has emerged as one of the most common health hazard all over the world. Diabetic nephropathy is the most challenging long term complication of Type 2 Diabetes mellitus and microalbuminuria is the earliest marker of diabetic nephropathy. In diabetes, chronic hyperglycemia and deranged lipid profile lead to excess generation of free radicals. The increased oxidative stress plays a major role in pathogenesis of diabetic complications, including diabetic nephropathy. There are many naturally occurring antioxidant enzymes in our body. Diabetes has multiple effects on protein levels and activity of these antioxidant enzymes. This further augments the oxidative stress. There are many non-enzymatic antioxidants in our body which include vitamins A, C, E and trace minerals like copper, zinc, manganese and selenium.Methods: The study was done on a total of 150 subjects. Group A comprised of 60 Type 2 diabetic patients with diabetic nephropathy, Group B comprised of 60 Type 2 diabetic patients without diabetic nephropathy and Group C comprised 30 healthy controls. Total antioxidant status, microalbuminuria and glycosylated haemoglobin were measured.Results: In present study, authors found that total antioxidant status is drastically reduced in all diabetic patients, and it was found to be further low in patients with diabetic nephropathy. This decrease was found to be directly proportional to the degree of diabetic nephropathy, as measured by the levels of microalbuminuria.Conclusions: Timely institution of antioxidant supplementation therapy may emerge as a promising measure in delaying the onset and progression of diabetic complications, especially diabetic nephropathy.


2021 ◽  
Vol 7 (2) ◽  
pp. 1-4
Author(s):  
Olatunde Olayanju ◽  
Victory Edem ◽  
Chika Okwor ◽  
Gabriel Odok ◽  
Nnaemeka Awah

Objective: Diabetes mellitus is associated with increased prevalence of oral diseases for which reactive oxygen species have been implicated. The saliva contains protective antioxidants which statutorily curtail these destructive oxygen molecules. A functional compromise of the antioxidants may precipitate oxidative stress leading to the increased oral disease susceptibility. However, salivary markers of oxidative stress have not been sufficiently studied in the diabetics. Methods: A total of 166 adults were recruited for this study. They comprised of 95 Type 2 diabetic patients and 71 healthy non-diabetic controls. About 3 ml of unstimulated saliva samples were collected from participants and processed, levels of salivary H2O2, NO and MDA were measured using spectrophotometry method and compared between the two groups. Data was analysed using t-test, logistic regression and receiver operating characteristics (ROC) with statistical significance set at p<0.05. Results: Salivary H2O2 (p=0.024) and NO (p=0.002) were significantly higher in the diabetic patients when compared to the healthy non-diabetic control group. Binary logistic regression showed that patients with Type 2 diabetic mellitus are more likely to have elevated salivary H2O2 (OR= 1.013; p=0.025) and NO (OR=1.016; p=0.003) levels. ROC analysis showed statistically significant performance of salivary NO levels in distinguishing between T2DM patients and healthy controls. Conclusions: Higher levels of oxidative stress markers including salivary H2O2 and NO in the diabetic groups could be a pointer to the characteristic high prevalence of oral diseases in diabetes mellitus, given that oxidative stress predisposes to disease vulnerability. This calls for increased attention to oral health in diabetes management to minimise co-morbidity.


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