scholarly journals Bariatric Surgery Reduces Visceral Adipose Inflammation and Improves Endothelial Function in Type 2 Diabetic Mice

2011 ◽  
Vol 31 (9) ◽  
pp. 2063-2069 ◽  
Author(s):  
Hanrui Zhang ◽  
Yong Wang ◽  
Jing Zhang ◽  
Barry J. Potter ◽  
James R. Sowers ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Endothelial Function ◽  
Diabetic Mice ◽  
Adipose Inflammation ◽  
Visceral Adipose ◽  
Type 2 Diabetic

Abstract 14372: Identification of the Genes That Are Involved in Severe Pulmonary Hypertension in Type 2 Diabetic Mice

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Qiuyu Zheng ◽  
Atsumi Tsuji-Hosokawa ◽  
Jody T Cabrera ◽  
Jian Wang ◽  
Ayako Makino
Keyword(s):  
Pulmonary Hypertension ◽  
Endothelial Function ◽  
Protein Level ◽  
Chronic Hypoxia ◽  
Systolic Pressure ◽  
Vascular Complications ◽  
Hypoxic Exposure ◽  
Diabetic Mice ◽  
Type 2 Diabetic

Pulmonary hypertension (PH) is a progressive disease characterized by increased pulmonary vascular resistance. Increasing evidence shows that diabetes increases the risks of PH, and diabetic priming leads to severe PH. However, the molecular mechanism by which preconditioning of diabetes results in severe PH is still unknown. It has been shown that endothelium serves as a key regulator of vascular tone, and endothelial cell dysfunction is implicated in the development of PH and diabetes-related vascular complications. Therefore, we identified the genes that contribute to the development of severe PH in diabetic mice with a focus on endothelial function. We first determined the effect of chronic hypoxia (10% O 2 , 4 weeks) on hemodynamics in type 2 diabetic (T2D) mice. We used inducible T2D mice (generated by high-fat diet and a low-dose streptozotocin injection) and spontaneous T2D mice (TALLYHO/Jng). Diabetic mice exhibited a slight increase in right ventricular systolic pressure (RVSP), and chronic hypoxia led to a further rise in RVSP in both inducible and spontaneous T2D mice. We isolated pulmonary endothelial cells (MPEC) from normoxia-exposed control mice (CN), hypoxia-exposed control mice (CH), normoxia-exposed diabetic mice (DN), and hypoxia-exposed diabetic mice (DH) to examine the levels of 92 genes using real-time PCR. Nighty two genes were selected based on their functions, which are significantly related to endothelial function. We found that 27 genes were significantly changed among 4 groups. We then examined the protein levels of genes that were related to apoptosis and glycolysis. Western Blot data indicated that the protein level of GAPDH was significantly increased in CH and DH compared to CN and DN. In addition, hypoxic exposure in diabetic mice (DH) significantly increased HK2 protein level compare to hypoxia-exposed control mice (CH). These data suggest that precondition of diabetes increases susceptibility to developing PH due partly to altering gene expression of HK2 and Gapdh in MPECs. Since HK2 and GAPDH are a crucial regulator of glycolysis, alteration of glycolysis is expected in hypoxia-exposed diabetic mice. Our study revealed the key molecules which could be used for treating severe PH in diabetes.

scholarly journals Adiponectin abates diabetes-induced endothelial dysfunction by suppressing oxidative stress, adhesion molecules, and inflammation in type 2 diabetic mice

2012 ◽  
Vol 303 (1) ◽  
pp. H106-H115 ◽  
Author(s):  
Sewon Lee ◽  
Hanrui Zhang ◽  
Jianping Chen ◽  
Kevin C. Dellsperger ◽  
Michael A. Hill ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Function ◽  
Total Cholesterol ◽  
Adhesion Molecules ◽  
Vascular Function ◽  
Serum Triglyceride ◽  
Diabetic Mice ◽  
Cholesterol Levels ◽  
Type 2 Diabetic

Adiponectin (APN) can confer protection against metabolism-related illnesses in organs such as fat, the liver, and skeletal muscle. However, it is unclear whether APN improves endothelial-dependent nitric oxide-mediated vasodilation in type 2 diabetes and, if so, by what mechanism. We tested whether exogenous APN delivery improves endothelial function in type 2 diabetic mice and explored the mechanisms underlying the observed improvement. To test the hypothesis, we injected adenovirus APN (Ad-APN) or adenovirus β-galactosidase (Ad-βgal; control virus) via the tail vein in control (m Lepr db) and diabetic (Lepr db; db/ db) mice and studied vascular function of the aorta ex vivo. Ad-APN improved endothelial-dependent vasodilation in db/ db mice compared with Ad-βgal, whereas Ad-APN had no further improvement on endothelial function in control mice. This improvement was completely inhibited by a nitric oxide synthase inhibitor ( NG-nitro-l-arginine methyl ester). Serum triglyceride and total cholesterol levels were increased in db/ db mice, and Ad-APN significantly reduced triglyceride levels but not total cholesterol levels. Immunoblot results showed that interferon-γ, gp91 phox, and nitrotyrosine were markedly increased in the aorta of db/ db mice. Ad-APN treatment decreased the expression of these proteins. In addition, mRNA expression of TNF-α, IL-6, and ICAM-1 was elevated in db/ db mice, and Ad-APN treatment decreased these expressions in the aorta. Our findings suggest that APN may contribute to an increase in nitric oxide bioavailability by decreasing superoxide production as well as by inhibiting inflammation and adhesion molecules in the aorta in type 2 diabetic mice.

scholarly journals Exercise training improves endothelial function via adiponectin-dependent and independent pathways in type 2 diabetic mice

2011 ◽  
Vol 301 (2) ◽  
pp. H306-H314 ◽  
Author(s):  
Sewon Lee ◽  
Yoonjung Park ◽  
Kevin C. Dellsperger ◽  
Cuihua Zhang
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Exercise Training ◽  
Endothelial Function ◽  
Protein Expression ◽  
Diabetic Mice ◽  
Ifn Γ ◽  
And Oxidative Stress ◽  
Type 2 Diabetic

Type 2 diabetes (T2D) is a leading risk factor for a variety of cardiovascular diseases including coronary heart disease and atherosclerosis. Exercise training (ET) has a beneficial effect on these disorders, but the basis for this effect is not fully understood. This study was designed to investigate whether the ET abates endothelial dysfunction in the aorta in T2D. Heterozygous controls (m Lepr db) and type 2 diabetic mice ( db/db; Lepr db) were either exercise entrained by forced treadmill exercise or remained sedentary for 10 wk. Ex vivo functional assessment of aortic rings showed that ET restored acetylcholine-induced endothelial-dependent vasodilation of diabetic mice. Although the protein expression of endothelial nitric oxide synthase did not increase, ET reduced both IFN-γ and superoxide production by inhibiting gp91phox protein levels. In addition, ET increased the expression of adiponectin (APN) and the antioxidant enzyme, SOD-1. To investigate whether these beneficial effects of ET are APN dependent, we used adiponectin knockout (APNKO) mice. Indeed, impaired endothelial-dependent vasodilation occurred in APNKO mice, suggesting that APN plays a central role in prevention of endothelial dysfunction. APNKO mice also showed increased protein expression of IFN-γ, gp91phox, and nitrotyrosine but protein expression of SOD-1 and -3 were comparable between wild-type and APNKO. These findings in the aorta imply that APN suppresses inflammation and oxidative stress in the aorta, but not SOD-1 and -3. Thus ET improves endothelial function in the aorta in T2D via both APN-dependent and independent pathways. This improvement is due to the effects of ET in inhibiting inflammation and oxidative stress (APN-dependent) as well as in improving antioxidant enzyme (APN-independent) performance in T2D.

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