scholarly journals Effects of Atorvastatin and Insulin in Vascular Dysfunction Associated With Type 2 Diabetes

2014 ◽  
pp. 189-197 ◽  
Author(s):  
C. M. SENA ◽  
P. MATAFOME ◽  
T. LOURO ◽  
E. NUNES ◽  
R. M. SEIÇA
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Endothelial Dysfunction ◽  
Vascular Reactivity ◽  
Vascular Dysfunction ◽  
Lipid Peroxides ◽  
Metabolic Parameters ◽  
Carbonyl Stress ◽  
Gk Rats

Atorvastatin and insulin have distinct mechanisms of action to improve endothelial function. Therefore, we hypothesized that atorvastatin and insulin therapies alone or in combination could have beneficial effects on endothelium-dependent vascular reactivity, oxidative stress, inflammation and metabolic parameters in Goto-Kakizaki (GK) rats, a model of type 2 diabetes fed with atherogenic diet (GKAD). In parallel with the development of diabetes and lipid profile, the generation of oxidative stress was determined by measurement of lipid peroxides and oxidized proteins and the presence of inflammation was evaluated by assessing C-reactive protein (CRP). Additionally, endothelial dependent and independent vascular sensitivity to acetylcholine and sodium nitroprusside were evaluated. GKAD showed increased carbonyl stress, inflammation, fasting glycemia, dyslipidemia and endothelial dysfunction when compared to control GK rats. Noteworthy, supplementation with insulin deteriorated endothelial dysfunction while atorvastatin induced an improvement. Atorvastatin and insulin therapies in combination improved metabolic parameters, CRP levels and insulin resistance indexes and ameliorated endothelial dysfunction in GKAD rats while they were unable to reduce urinary 8-isoprostranes and plasma carbonyl compounds. The therapeutic association of atorvastatin and insulin provided a better metabolic control with a reduction in endothelial dysfunction in GKAD rats by a mechanism that involves an improvement in systemic inflammation.

scholarly journals Luteolin Improves Perivascular Adipose Tissue Profile and Vascular Dysfunction in Goto-Kakizaki Rats

2021 ◽  
Vol 22 (24) ◽  
pp. 13671
Author(s):  
Marcelo Queiroz ◽  
Adriana Leandro ◽  
Lara Azul ◽  
Artur Figueirinha ◽  
Raquel Seiça ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Endothelial Function ◽  
Metabolic Parameters ◽  
Perivascular Adipose Tissue ◽  
Gk Rats ◽  
Vascular Oxidative Stress ◽  
Luteolin Treatment

We investigated the effects of luteolin on metabolism, vascular reactivity, and perivascular adipose tissue (PVAT) in nonobese type 2 diabetes mellitus animal model, Goto-Kakizaki (GK) rats. Methods: Wistar and GK rats were divided in two groups: (1) control groups treated with vehicle; (2) groups treated with luteolin (10 mg/kg/day, for 2 months). Several metabolic parameters such as adiposity index, lipid profile, fasting glucose levels, glucose and insulin tolerance tests were determined. Endothelial function and contraction studies were performed in aortas with (PVAT+) or without (PVAT−) periaortic adipose tissue. We also studied vascular oxidative stress, glycation and assessed CRP, CCL2, and nitrotyrosine levels in PVAT. Results: Endothelial function was impaired in diabetic GK rats (47% (GK − PVAT) and 65% (GK + PVAT) inhibition of maximal endothelial dependent relaxation) and significantly improved by luteolin treatment (29% (GK − PVAT) and 22% (GK + PVAT) inhibition of maximal endothelial dependent relaxation, p < 0.01). Vascular oxidative stress and advanced glycation end-products’ levels were increased in aortic rings (~2-fold, p < 0.05) of diabetic rats and significantly improved by luteolin treatment (to levels not significantly different from controls). Periaortic adipose tissue anti-contractile action was significantly rescued with luteolin administration (p < 0.001). In addition, luteolin treatment significantly recovered proinflammatory and pro-oxidant PVAT phenotype, and improved systemic and metabolic parameters in GK rats. Conclusions: Luteolin ameliorates endothelial dysfunction in type 2 diabetes and exhibits therapeutic potential for the treatment of vascular complications associated with type 2 diabetes.

Hyperglycemia causes oxidative stress in pancreatic beta-cells of GK rats, a model of type 2 diabetes

Diabetes ◽  
1999 ◽  
Vol 48 (4) ◽  
pp. 927-932 ◽  
Author(s):  
Y. Ihara ◽  
S. Toyokuni ◽  
K. Uchida ◽  
H. Odaka ◽  
T. Tanaka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Gk Rats

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

Chronic consumption of an inositol-enriched beverage ameliorates endothelial dysfunction and oxidative stress in type 2 diabetes

2015 ◽  
Vol 18 ◽  
pp. 598-607 ◽  
Author(s):  
Antonio Hernández-Mijares ◽  
Celia Bañuls ◽  
Susana Rovira-Llopis ◽  
Ángeles Álvarez ◽  
Samuel Orden ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Endothelial Dysfunction ◽  
And Oxidative Stress

scholarly journals Inhibition of Protein Kinase Cβ Does Not Improve Endothelial Function in Type 2 Diabetes

2010 ◽  
Vol 95 (8) ◽  
pp. 3783-3787 ◽  
Author(s):  
Joshua A. Beckman ◽  
Allison B. Goldfine ◽  
Alison Goldin ◽  
Adnan Prsic ◽  
Sora Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Healthy Subjects ◽  
Vascular Dysfunction ◽  
Endothelial Damage ◽  
Markers Of Inflammation ◽  
Resistance Vessels ◽  
Healthy Control ◽  
And Oxidative Stress

Context: Antagonism of protein kinase Cβ (PKCβ) restores endothelial function in experimental models of diabetes and prevents vascular dysfunction in response to hyperglycemia in healthy humans. Objective: We tested the hypothesis that PKCβ antagonism would improve vascular function in subjects with type 2 diabetes compared with healthy control subjects. Design: The effect of PKCβ was evaluated in a randomized, placebo-controlled, double-blinded crossover trial. Setting: The study was performed in the outpatient setting of a university medical center. Participants: Thirteen subjects with type 2 diabetes without evidence of cardiovascular disease and 15 healthy control subjects were recruited via newspaper advertisement. Intervention: Subjects underwent a randomized, double-blind, crossover, placebo-controlled trial of the selective PKCβ antagonist ruboxistaurin mesylate. Subjects received each treatment for 14 d. Main Outcome Measure: Endothelium-dependent and endothelium-independent vasodilation of forearm resistance vessels was measured with mercury-in-silastic, strain-gauge plethysmography during intraarterial administration of methacholine chloride and verapamil, respectively. Markers of inflammation, fibrinolysis, endothelial damage, and oxidative stress were measured after each treatment. Results: Endothelium-dependent vasodilation of forearm resistance vessels was attenuated in diabetic subjects when compared with healthy subjects (P = 0.001). Endothelium-independent vasodilation did not differ between groups (P value not significant). Ruboxistaurin did not significantly change endothelium-dependent or endothelium-independent vasodilation or blood-based markers of inflammation, fibrinolysis, endothelial damage, and oxidative stress in either diabetic or healthy subjects. Conclusion: Endothelial dysfunction of forearm resistance vessels was not improved by 2 wk of selective PKCβ inhibition in patients with diabetes. These results suggest that PKCβ does not contribute significantly to vascular dysfunction in otherwise healthy patients with type 2 diabetes.

scholarly journals Differential Telomere Shortening in Blood versus Arteries in an Animal Model of Type 2 Diabetes

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Samira Tajbakhsh ◽  
Kamelya Aliakbari ◽  
Damian J. Hussey ◽  
Karen M. Lower ◽  
Anthony J. Donato ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Type 2 Diabetes ◽  
Vascular Dysfunction ◽  
Vascular Complications ◽  
Sirtuin 1 ◽  
Telomere Shortening ◽  
Telomere Attrition ◽  
Clinical Complications

Vascular dysfunction is an early feature of diabetic vascular disease, due to increased oxidative stress and reduced nitric oxide (NO) bioavailability. This can lead to endothelial cell senescence and clinical complications such as stroke. Cells can become senescent by shortened telomeres and oxidative stress is known to accelerate telomere attrition. Sirtuin 1 (SIRT1) has been linked to vascular health by upregulating endothelial nitric oxide synthase (eNOS), suppressing oxidative stress, and attenuating telomere shortening. Accelerated leukocyte telomere attrition appears to be a feature of clinical type 2 diabetes (T2D) and therefore the telomere system may be a potential therapeutic target in preventing vascular complications of T2D. However the effect of T2D on vascular telomere length is currently unknown. We hypothesized that T2D gives rise to shortened leukocyte and vascular telomeres alongside reduced vascular SIRT1 expression and increased oxidative stress. Accelerated telomere attrition was observed in circulating leukocytes, but not arteries, in T2D compared to control rats. T2D rats had blunted arterial SIRT1 and eNOS protein expression levels which were associated with reduced antioxidant defense capacity. Our findings suggest that hyperglycemia and a deficit in vascular SIRT1per seare not sufficient to prematurely shorten vascular telomeres.

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