Augmented NADPH oxidase activity and p22phox expression in monocytes underlie oxidative stress of patients with type 2 diabetes mellitus

2011 ◽  
Vol 91 (3) ◽  
pp. 371-380 ◽  
Author(s):  
Xiuqing Huang ◽  
Mingxiao Sun ◽  
Dongxiao Li ◽  
Jin Liu ◽  
Hanbang Guo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Nadph Oxidase Activity

Abstract P048: Effects of Aerobic Exercise on Oxidative Stress in the Kidneys of Type2 Diabetic Rats

Circulation ◽  
2016 ◽  
Vol 133 (suppl_1) ◽  
Author(s):  
Daisuke Ito ◽  
Pengyu Cao ◽  
Takaaki Kakihana ◽  
Emiko Sato ◽  
Yoshikazu Muroya ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Aerobic Exercise ◽  
Nadph Oxidase Activity ◽  
Beneficial Effects ◽  
Significant Difference ◽  
Zdf Rats

Objective: Aerobic exercise is known to have multiple beneficial effects including renal protection in type 2 diabetes mellitus and obesity. However, the mechanisms regulating these actions of aerobic exercise remain unclear. The present study evaluated the effects of chronic aerobic exercise on early stage of diabetic nephropathy focusing on renal oxidative stress and nitric oxide (NO), using Zucker diabetic fatty (ZDF) rats as an animal model of obese type 2 diabetes. Methods: Male ZDF rats (6 weeks old) underwent forced treadmill exercise for 8 weeks (Ex-ZDF). Sedentary ZDF (Sed-ZDF) and Zucker lean (Sed-ZL) rats served as controls. After the last exercise session, all rats were subjected to an intra-peritoneal glucose tolerance test. Result: Exercise ameliorated hyperglycemia with increased insulin secretion, and raised the values of homeostasis model assessment for β-cell function (HOMA-β) in ZDF rats. Exercise also reduced albumin excretion and normalized creatinine clearance in ZDF rats. Endothelial (e) and neuronal (n) NO synthase (NOS) protein expression, and NOS activity in the kidneys of Sed-ZDF rats were lower compared with Sed-ZL rats, while both NOS expression and NOS activity were upregulated by exercise in ZDF rats. Although there was no significant difference in plasma levels of adiponectin between the groups, plasma levels of leptin were significantly higher in the Ex-ZDF group compared with the Sed-ZL and Sed-ZDF groups. Exercise decreased plasma and urinary thiobarbituric acid-reactive substances (TBARS) as an index of lipid peroxidation in ZDF rats. Additionally, renal nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and expression of p47phox protein were significantly higher in the kidneys of the Sed-ZDF group compared with the Sed-ZL group, and there was no significant difference between the Ex-ZDF and Sed-ZL groups. Immunoblots for Nox4, Nox2, namely gp91phox and p22phox protein were undetected in the kidneys of the Sed-ZDF and Ex-ZDF group as well as the Sed-ZL group. In addition, expression of nitrotyrosine as an index of peroxynitrite (ONOO–) formation was significantly lower in the kidneys of the Sed-ZDF group compared with the Sed-ZL group, and was significantly higher in the Ex-ZDF group compared with the Sed-ZDF group. Further, morphometric evidence of renal damage was alleviated in response to exercise. Conclusion: Upregulated NOS activity and NOS protein, and ameliorated NADPH oxidase activity and p47phox protein in the kidneys may be potential mechanisms by which chronic aerobic exercise can reduced early diabetic nephropathy in ZDF rats. Chronic aerobic exercise does have beneficial effects and may be a novel therapeutic approach for preventing the development of renal dysfunction in patients with type 2 diabetes mellitus and obesity.

scholarly journals Synergistic Effects of Milk-Derived Exosomes and Galactose on α-Synuclein Pathology in Parkinson’s Disease and Type 2 Diabetes Mellitus

2021 ◽  
Vol 22 (3) ◽  
pp. 1059
Author(s):  
Bodo C. Melnik
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Dopaminergic Neurons ◽  
Vagal Nerve ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
The Brain

Epidemiological studies associate milk consumption with an increased risk of Parkinson’s disease (PD) and type 2 diabetes mellitus (T2D). PD is an α-synucleinopathy associated with mitochondrial dysfunction, oxidative stress, deficient lysosomal clearance of α-synuclein (α-syn) and aggregation of misfolded α-syn. In T2D, α-syn promotes co-aggregation with islet amyloid polypeptide in pancreatic β-cells. Prion-like vagal nerve-mediated propagation of exosomal α-syn from the gut to the brain and pancreatic islets apparently link both pathologies. Exosomes are critical transmitters of α-syn from cell to cell especially under conditions of compromised autophagy. This review provides translational evidence that milk exosomes (MEX) disturb α-syn homeostasis. MEX are taken up by intestinal epithelial cells and accumulate in the brain after oral administration to mice. The potential uptake of MEX miRNA-148a and miRNA-21 by enteroendocrine cells in the gut, dopaminergic neurons in substantia nigra and pancreatic β-cells may enhance miRNA-148a/DNMT1-dependent overexpression of α-syn and impair miRNA-148a/PPARGC1A- and miRNA-21/LAMP2A-dependent autophagy driving both diseases. MiRNA-148a- and galactose-induced mitochondrial oxidative stress activate c-Abl-mediated aggregation of α-syn which is exported by exosome release. Via the vagal nerve and/or systemic exosomes, toxic α-syn may spread to dopaminergic neurons and pancreatic β-cells linking the pathogenesis of PD and T2D.

scholarly journals GTP Cyclohydrolase I Gene Polymorphisms Are Associated with Endothelial Dysfunction and Oxidative Stress in Patients with Type 2 Diabetes Mellitus

PLoS ONE ◽  
2014 ◽  
Vol 9 (11) ◽  
pp. e108587 ◽  
Author(s):  
Pawel P. Wolkow ◽  
Wladyslaw Kosiniak-Kamysz ◽  
Grzegorz Osmenda ◽  
Grzegorz Wilk ◽  
Beata Bujak-Gizycka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Gene Polymorphisms ◽  
Gtp Cyclohydrolase I ◽  
And Oxidative Stress ◽  
I Gene

scholarly journals Oxidative stress in patients with type 2 diabetes mellitus treated with metformin

2017 ◽  
Vol 27 (2) ◽  
pp. 25857
Author(s):  
Samuel Selbach Dries ◽  
Bárbara Da Silveira Soares ◽  
Ana Luiza Ziulkoski ◽  
Simone Gasparin Verza ◽  
Rafael Linden ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Superoxide Dismutase ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Side Effects ◽  
Diabetic Complications

*** Oxidative stress in patients with type 2 diabetes mellitus treated with metformin ***AIMS: To evaluate oxidative stress parameters in patients with type 2 diabetes mellitus treated with metformin, relating these values to its side effects, plasma levels, glycemic control, diabetic complications, lipid profile, and the influence of pharmacotherapeutic follow-up.METHODS: Patients with type 2 diabetes mellitus, on metformin and in pharmacotherapeutic follow-up for four months, were evaluated. The pharmacotherapeutic follow-up consisted in providing information and answering patients’ questions about medication and disease. In addition, administration times, dosages, and presence or absence of side effects related to the use of metformin were verified. Glycemic and lipid profile, oxidative stress (superoxide dismutase and malondialdehyde) and plasma metformin were evaluated. Pearson’s correlation and Spearman’s correlation were performed to evaluate the relationship between the variables at the beginning of the study. The independent t-test and Mann-Whitney U test were used to assess the difference between the groups with and without diabetic complications. The range of values between the beginning and  end of the study was evaluated using Student’s t-test or Wilcoxon U test. The significance level was set at 5%.RESULTS: The initial sample consisted of 49 patients aged 59±9 years with a body mass index of 29.8±5.1 kg/m2, who have had diabetes for a median time of 36 months (interquartile range of 1-240) and have been on metformin for a median time of 36 months (interquartile range of 1-180). Twenty-five patients left the study between the second and fourth meetings. Malondialdehyde levels differed between before and after pharmacotherapeutic follow-up, being positively correlated with blood glucose, glycohemoglobin, and triglyceride level, and negatively correlated with metformin and superoxide dismutase. Blood glucose, glycohemoglobin, and malondialdehyde levels increased, whereas metformin levels decreased in the group with diabetic complications, and there was a correlation between malondialdehyde and the number of diabetic complications per patient.CONCLUSIONS: In this sample of patients with type 2 diabetes mellitus treated with metformin, oxidative stress was more pronounced in those with poor glycemic control and diabetic complications.

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