Elevated branched-chain α-keto acids exacerbate macrophage oxidative stress and chronic inflammatory damage in type 2 diabetes mellitus

2021 ◽  
Vol 175 ◽  
pp. 141-154
Author(s):  
Shuyun Liu ◽  
Ling Li ◽  
Peng Lou ◽  
Meng Zhao ◽  
Yizhuo Wang ◽  
...  
2021 ◽  
Vol 22 (3) ◽  
pp. 1059
Author(s):  
Bodo C. Melnik

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.


PLoS ONE ◽  
2014 ◽  
Vol 9 (11) ◽  
pp. e108587 ◽  
Author(s):  
Pawel P. Wolkow ◽  
Wladyslaw Kosiniak-Kamysz ◽  
Grzegorz Osmenda ◽  
Grzegorz Wilk ◽  
Beata Bujak-Gizycka ◽  
...  

2017 ◽  
Vol 27 (2) ◽  
pp. 25857
Author(s):  
Samuel Selbach Dries ◽  
Bárbara Da Silveira Soares ◽  
Ana Luiza Ziulkoski ◽  
Simone Gasparin Verza ◽  
Rafael Linden ◽  
...  

*** 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.


2019 ◽  
Vol 09 (03) ◽  
pp. 232-236
Author(s):  
Shabzain Ishrat ◽  
Talea Hoor ◽  
Mohammed Sajid Abbas Jaffri

Type 2 diabetes mellitus (DM) is a chronic disease which deteriorates the quality of life with time. Type 2 DM accounts for more than 90% cases of diabetes mellitus as compared to other types of this disease. There is significant oxidative stress in type 2 DM which plays an important role in the pathogenesis of disease. In order to combat this oxidative stress antioxidant supplements have to be added as add on therapy along with treatment of type 2 DM. Vitamin C is the safest antioxidant which plays significant role in diminishing the oxidative stress. The vitamin C supplementation have good control of FBS and HbA1c and therefore helps in achieving better glycemic control along with prevention of lipid abnormalities.


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