scholarly journals Elevated reactive oxygen species and increased mononuclear NADPH oxidase expression in type 2 diabetes patients

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Shekhar H Deo ◽  
Matthew C Zimmerman ◽  
Paul J Fadel
Keyword(s):  
Reactive Oxygen Species ◽  
Type 2 Diabetes ◽  
Nadph Oxidase ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Diabetes Patients

Reactive oxygen species-selective regulation of aortic inflammatory gene expression in Type 2 diabetes

2007 ◽  
Vol 292 (5) ◽  
pp. H2073-H2082 ◽  
Author(s):  
Alejandra San Martín ◽  
Pingfeng Du ◽  
Anna Dikalova ◽  
Bernard Lassègue ◽  
María Aleman ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Type 2 Diabetes ◽  
Nadph Oxidase ◽  
Vascular Inflammation ◽  
Reactive Oxygen ◽  
Vascular Diseases ◽  
Tissue Growth ◽  
Ros Production ◽  
Oxygen Species

Vascular diseases are a major complication of diabetes mellitus (DM), although their etiology is poorly understood. NADPH oxidase-derived reactive oxygen species (ROS) production and inflammation are potential mediators of DM-associated vascular diseases. Using db/db mice as a Type 2 diabetes model, we examined the relationship between NADPH oxidase-derived ROS and vascular inflammation. When compared with control m+/+ mice, aortas from 4- and 12-wk-old db/db mice had higher NADPH oxidase activity and increased superoxide levels, leading to NADPH oxidase-dependent impaired vasodilation at 12 wk. Diabetes progression from 4 to 12 wk led to increased Nox1, Nox4, and p22 phox subunit mRNAs and induced the expression of a group of matrix remodeling-related cytokines: connective tissue growth factor (CTGF), bone morphogenetic protein 4 (BMP-4), and osteopontin (OPN). After 8 wk of treatment with the superoxide scavenger Tempol, 12-wk-old db/db mice had lower superoxide production, reduced plasma glucose and lipids, and lower BMP-4 and OPN protein expression when compared with nontreated mice. No changes were observed with Tempol in CTGF or m+/+ mice. The ability of Tempol to reverse ROS production as well as OPN and BMP-4, but not CTGF, induction suggests that DM-induced vascular inflammation involves both ROS-sensitive and -insensitive pathways.

scholarly journals CREBRF p.Arg457Gln Promotes Obesity and Improves Insulin Sensitivity by Promoting Preadipocyte Differentiation and Reducing Oxidative Metabolism in Gene-modified Pig Models

2021 ◽  
Author(s):  
Yingying Li ◽  
Hai Wang ◽  
Yuan Liao ◽  
Quanmei Yan ◽  
Zhen Ouyang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Oxidative Metabolism ◽  
Reactive Oxygen ◽  
Oxidative Capacity ◽  
Oxygen Species ◽  
Preadipocyte Differentiation ◽  
Human Mutation

Abstract Obesity is one of the most important risk factors for type 2 diabetes (T2DM). The CREBRF missense allele of rs373863828 (p.Arg457Gln) is associated with increased body mass index (BMI), yet reduced risk of T2DM in people with Pacific ancestry. To investigate the functional consequences of the CREBRF variant, we introduced the corresponding human mutation p.Arg457Gln into porcine genome by using a CRISPR/Cas9-mediated homologous recombination (HR)-dependent approach. The CREBRF p.Arg457Gln pig models displayed dramatically increased fat deposition, yet improved sensitivity to insulin. Transcriptome and metabolome analyses of subcutaneous white adipose tissues showed that the CREBRF p.Arg457Gln mutation promoted preadipocyte differentiation, which indicated that obesity was caused by increased number (hyperplasia) rather than size (hypertrophy) of adipocytes. In addition, the oxidative capacity decreased in the adipose tissue of pigs with CREBRF p.Arg457Gln variant. The pre-oxidative metabolite content (4-HNE and MDA) significantly decreased, while activity of antioxidant enzymes (GPX, SOD, and CAT) increased, thereby repressing oxidative metabolism of adipose tissue and reducing level of reactive oxygen species (ROS). The low reactive oxygen species could prevent insulin resistance and reduce risk of obesity-induced type 2 diabetes. This study provides further mechanistic insights into favourable adiposity resulting from CREBRF p.Arg457Gln.

scholarly journals Role of Perivascular Adipose Tissue on Vascular Reactive Oxygen Species in Type 2 Diabetes: A Give-and-Take Relationship: Figure 1

Diabetes ◽  
2015 ◽  
Vol 64 (6) ◽  
pp. 1904-1906 ◽  
Author(s):  
Jaume Padilla ◽  
Victoria J. Vieira-Potter ◽  
Guanghong Jia ◽  
James R. Sowers
Keyword(s):  
Reactive Oxygen Species ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Perivascular Adipose Tissue

scholarly journals Effects of Naringin on Cardiomyocytes From a Rodent Model of Type 2 Diabetes

2021 ◽  
Vol 12 ◽  
Author(s):  
A. Uryash ◽  
A. Mijares ◽  
V. Flores ◽  
J. A. Adams ◽  
J. R. Lopez
Keyword(s):  
Reactive Oxygen Species ◽  
Type 2 Diabetes ◽  
Cell Viability ◽  
Glucose Transport ◽  
Reactive Oxygen ◽  
Nitric Oxide Donor ◽  
Diabetic Patients ◽  
Oxygen Species ◽  
Calpain Activity

Diabetic cardiomyopathy (DCM) is a primary disease in diabetic patients characterized by diastolic dysfunction leading to heart failure and death. Unfortunately, even tight glycemic control has not been effective in its prevention. We have found aberrant diastolic Ca2+ concentrations ([Ca2+]d), decreased glucose transport, elevated production of reactive oxygen species (ROS), and increased calpain activity in cardiomyocytes from a murine model (db/db) of type 2 diabetes (T2D). Cardiomyocytes from these mice demonstrate significant cell injury, increased levels of tumor necrosis factor-alpha and interleukin-6 and expression of the transcription nuclear factor-κB (NF-κB). Furthermore, decreased cell viability, and reduced expression of Kir6.2, SUR1, and SUR2 subunits of the ATP-sensitive potassium (KATP) channels. Treatment of T2D mice with the citrus fruit flavonoid naringin for 4 weeks protected cardiomyocytes by reducing diastolic Ca2+ overload, improving glucose transport, lowering reactive oxygen species production, and suppressed myocardial inflammation. In addition, naringin reduced calpain activity, decreased cardiac injury, increased cell viability, and restored the protein expression of Kir6.2, SUR1, and SUR2 subunits of the KATP channels. Administration of the KATP channel inhibitor glibenclamide caused a further increase in [Ca2+]d in T2D cardiomyocytes and abolished the naringin effect on [Ca2+]d. Nicorandil, a KATP channel opener, and nitric oxide donor drug mimic the naringin effect on [Ca2+]d in T2D cardiomyocyte; however, it aggravated the hyperglycemia in T2D mice. These data add new insights into the mechanisms underlying the beneficial effects of naringin in T2D cardiomyopathy, thus suggesting a novel approach to treating this cardiovascular complication.

scholarly journals HEPATIC SOD1 GENE EXPRESSION CHANGES IN THE NAFLD PATHOGENESIS IN OBESITY

2021 ◽  
Vol 23 (4) ◽  
pp. 761-766
Author(s):  
A. A. Komar ◽  
D. A. Shunkina (Skuratovsvkaia) ◽  
M. A. Vulf ◽  
H. Q. Vu ◽  
N. M. Todosenko ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Type 2 Diabetes ◽  
Copy Number ◽  
Tricarboxylic Acid Cycle ◽  
Reactive Oxygen ◽  
Metabolic Adaptation ◽  
Control Group ◽  
Obese Patients ◽  
Oxygen Species

Steatosis in the liver in obesity increases the work of mitochondria to utilize excess lipids. An overload of β-oxidation of fatty acids, the tricarboxylic acid cycle, and oxidative phosphorylation leads to a decrease in ATP and an increase in the formation of reactive oxygen species. Normally, mitochondria can efficiently remove elevated levels of reactive oxygen species using the cell's antioxidant system and metabolic adaptation to altered conditions. This study aimed to investigate the role of hepatic SOD expression in the pathogenesis of NAFLD in obesity. It was found that the level of SOD1 expression in the liver in obese patients with and without type 2 diabetes with a BMI > 40 kg/m2 was lower than in healthy donors. The copy number of mitochondrial DNA (mtDNA) in the liver in all obese patients was more than two times lower than in the control group. In the liver of obese patients without type 2 diabetes, the SOD1 protein level and the mtDNA copy number were interrelated and negatively correlated with the area of fatty inclusions. Thus, in obese patients, a decrease in antioxidant defense in the liver leads to the vulnerability of mitochondria, which, in turn, contributes to the progression of steatosis and insulin resistance.

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