scholarly journals Transfer of a human gene variant associated with exceptional longevity improves cardiac function in obese type 2 diabetic mice through induction of the SDF ‐1/ CXCR4 signalling pathway

2020 ◽  
Vol 22 (9) ◽  
pp. 1568-1581 ◽  
Author(s):  
Zexu Dang ◽  
Elisa Avolio ◽  
Anita C. Thomas ◽  
Ashton Faulkner ◽  
Antonio P. Beltrami ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Human Gene ◽  
Signalling Pathway ◽  
Gene Variant ◽  
Diabetic Mice ◽  
Exceptional Longevity ◽  
Type 2 Diabetic

scholarly journals CD133+Exosome Treatment Improves Cardiac Function after Stroke in Type 2 Diabetic Mice

2020 ◽  
Author(s):  
Poornima Venkat ◽  
Chengcheng Cui ◽  
Zhili Chen ◽  
Michael Chopp ◽  
Alex Zacharek ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Diabetic Mice ◽  
Type 2 Diabetic

Abstract 279: Stromal Cell-derived Factor-1 Prevents From Diabetic Cardiomyopathy via Cxcr7/ampk-mediated Nrf2 Activation in Type 2 Diabetic Mice

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Shudong Wang ◽  
Junlian Gu ◽  
Xiaoqing Yan ◽  
Jing Chen ◽  
Jun Chen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Cardiac Function ◽  
Stromal Cell ◽  
Normal Diet ◽  
Diabetic Mice ◽  
Nrf2 Activation ◽  
Stromal Cell Derived Factor ◽  
Type 2 Diabetic

We have demonstrated that stromal cell-derived factor 1(SDF-1) protects against palmitate-induced cardiac cell death via CXCR7-mediated activation of AMPK signaling (Diabetes 62:2545-2558, 2013). Whether SDF-1 prevents diabetic cardiomyopathy (DCM) and what the underlying mechanism has not been addressed. Here we evaluated the prevention of SDF-1 from DCM in a high fat diet plus streptozotocin (HFD/STZ)-induced type 2 diabetic model in C57BL/6J mice. After 1 month on HFD, the HFD-fed mice were injected with one low dose STZ (100mg/kg body weight, ip). Five days after STZ injection, mice with blood glucose levels ≥250 mg/dl were defined as diabetic. In parallel, the age-matched normal diet-fed mice injected with a same volume of vehicle were used as control. After onset of diabetes, the mice were maintained on HFD or normal diet for another 4 months with or without SDF-1 treatment. Then cardiac function was assayed again, and the mice were sacrificed and cardiac tissue collected for cardiomyopathic index assay. We found that 1 month HFD feeding induced a significant insulin resistance without effect on cardiac function, but continued HFD feeding after STZ injection significantly increased insulin resistance and blood glucose, as well as blood insulin, triglyceride and cholesterol levels. Furthermore, HFD/STZT significantly impaired cardiac function, which were accompanied by increased cardiac inflammation, oxidative stress and fibrotic remodeling. Treatment with SDF-1 dose-dependently prevented diabetes-induced cardiac dysfunction, inflammation and remodeling, but without significant effects on the above mentioned other pathophysiological changes. Mechanistic study demonstrated that diabetes significantly inhibited the function of AMPK and Nrf2, and the expression of CXCR7, but not CXCR4; while treatment with SDF-1 significantly preserved AMPK and Nrf2 function and CXCR7 expression. Knockout CXCR4 did not affect SDF-1 preservation of AMPK and Nrf2 function, but SiRNA knockdown of AMPK resulted in blockade of SDF-1 preservation of Nrf2 function. These results indicate that SDF-1 prevents from DCM via CXCR7/AMPK-mediated Nrf2 activation in type 2 diabetic mice.

scholarly journals Chronic Cadmium Exposure Aggravates the Cardiac Dysfunction in Type 2 Diabetic Mice by Promoting Inflammation and Fibrosis

2021 ◽  
Author(s):  
Xiuxiu Liu ◽  
Shuai Wang ◽  
Mengyang Li ◽  
Jiafu Li ◽  
Zhijie Sheng ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Natriuretic Peptide ◽  
Transforming Growth Factor ◽  
Troponin T ◽  
Exposure Level ◽  
Diabetic Mice ◽  
Cd Exposure ◽  
Experimental Group ◽  
Type 2 Diabetic

Abstract Background: Diabetic cardiomyopathy (DCM) is a serious diabetic complication with high mortality. Cadmium (Cd) is a ubiquitous environmental contaminant and plays an important role in cardiac lesions. However, whether Cd aggravates DCM is debatable. In the present study, the effects of chronic Cd exposure on cardiomyopathy in normal and type 2 diabetic mice were investigated. Methods: Sixty male C57BL/6J mice were randomly divided into four groups: blank control (normal mice without Cd exposure), Cd control (normal mice with Cd exposure, exposure level 1.74-2.45 mg/kg/day), diabetic mice control (diabetic mice without Cd exposure) and experimental group (diabetic mice with Cd exposure, exposure level 1.37-3.58 mg/kg/day). After 16 weeks Cd exposure, echocardiography was performed to determine cardiac structure and function. Other outcomes measures included myocardial injury, inflammation and fibrosis. Results: Cd damaged the cardiac function by decreased EF% (ejection fraction) and FS% (fractional shortening) and increased concentration of cTnT (cardiac troponin T) and the expressions of BNP (brain natriuretic peptide) and ANP (atrial natriuretic peptide) in normal mice. For experimental group, the expression of IL-1 (Interleukin-1), TNF-α (tumor necrosis factor-alpha), MCP-1 (monocyte chemotactic protein 1), FN (fibronectin) and TGF-β1 (transforming growth factor-β1) were significantly increased, indicating that Cd promoted the accumulations of fibrosis and inflammation in diabetic mice. In terms of cardiac function, compared with normal mice, the cardiac injury marker of experimental mice was increased and the myocardial contractility was further attenuate, suggesting diabetic mice were more sensitive than normal mice when exposed to cadmium. Conclusion: Cd could damage the heart contractility and aggravate the disruption of cardiac function in diabetic mice by deteriorating inflammation and fibrosis.

Effects of Lactobacillus casei CCFM419 on insulin resistance and gut microbiota in type 2 diabetic mice

2017 ◽  
Vol 8 (3) ◽  
pp. 421-432 ◽  
Author(s):  
X. Li ◽  
E. Wang ◽  
B. Yin ◽  
D. Fang ◽  
P. Chen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Gut Microbiota ◽  
Lactobacillus Casei ◽  
Short Chain Fatty Acids ◽  
Signalling Pathway ◽  
Short Chain ◽  
Diabetic Mice ◽  
Type 2 Diabetic

The antidiabetic effect of Lactobacillus is increasingly recognized worldwide. In this research, the hypoglycemic activity of Lactobacillus casei CCFM419 was investigated in mice with high-fat and low-dose streptozotocin induced type 2 diabetes. Oral L. casei CCFM419 administration favourably regulated blood glucose balance, increased glucose tolerance and protected islets in the diabetic mice, accompanied by an improvement in lipid metabolism. The homeostasis model of insulin resistance, insulin level and insulin tolerance test and mRNA expression of PI3K/Akt signalling pathway indexes revealed that L. casei CCFM419 had a positive effect on insulin resistance. Furthermore, treatment with L. casei CCFM419 recovered the level of short-chain fatty acids and increased the abundance of butyrate-producing bacteria, such as Allobaculum and Bacteriodes. These results demonstrated that L. casei CCFM419 had the potential ability to ameliorate insulin resistance and hyperglycaemic in type 2 diabetic mice through underlying PI3K/Akt signalling pathway and short-chain fatty acids/gut microbiota pathways.

scholarly journals Mammalian Target of Rapamycin (mTOR) Inhibition with Rapamycin Improves Cardiac Function in Type 2 Diabetic Mice

2013 ◽  
Vol 289 (7) ◽  
pp. 4145-4160 ◽  
Author(s):  
Anindita Das ◽  
David Durrant ◽  
Saisudha Koka ◽  
Fadi N. Salloum ◽  
Lei Xi ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Diabetic Mice ◽  
Mtor Inhibition ◽  
Type 2 Diabetic

scholarly journals Vildagliptin Attenuates Myocardial Dysfunction and Restores Autophagy via miR-21/SPRY1/ERK in Diabetic Mice Heart

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaochen Li ◽  
Cheng Meng ◽  
Fei Han ◽  
Juhong Yang ◽  
Jingyu Wang ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Diabetic Cardiomyopathy ◽  
High Glucose ◽  
Myocardial Dysfunction ◽  
Mammalian Target Of Rapamycin ◽  
Major Adverse Cardiovascular Events ◽  
H9c2 Cells ◽  
Diabetic Mice ◽  
Type 2 Diabetic

Aim: Vildagliptin (vild) improves diastolic dysfunction and is associated with a lower relative risk of major adverse cardiovascular events in younger patients. The present study aimed to evaluate whether vild prevents the development of diabetic cardiomyopathy in type 2 diabetic mice and identify its underlying mechanisms.Methods: Type 2 diabetic mouse model was generated using wild-type (WT) (C57BL/6J) and miR-21 knockout mice by treatment with HFD/STZ. Cardiomyocyte-specific miR-21 overexpression was achieved using adeno-associated virus 9. Echocardiography was used to evaluate cardiac function in mice. Morphology, autophagy, and proteins levels in related pathway were analyzed. qRT-PCR was used to detect miR-21. Rat cardiac myoblast cell line (H9c2) cells were transfected with miR-21 mimics and inhibitor to explore the related mechanisms of miR-21 in diabetic cardiomyopathy.Results: Vild restored autophagy and alleviated fibrosis, thereby enhancing cardiac function in DM mice. In addition, miR-21 levels were increased under high glucose conditions. miR-21 knockout DM mice with miR-21 knockout had reduced cardiac hypertrophy and cardiac dysfunction compared to WT DM mice. Overexpression of miR-21 aggravated fibrosis, reduced autophagy, and attenuated the protective effect of vild on cardiac function. In high-glucose-treated H9c2 cells, the downstream effectors of sprouty homolog 1 (SPRY1) including extracellular signal-regulated kinases (ERK) and mammalian target of rapamycin showed significant changes following transfection with miR-21 mimics or inhibitor.Conclusion: The results of our study indicate that vild prevents DCM by restoring autophagy through the miR-21/SPRY1/ERK/mTOR pathway. Therefore, miR-21 is a target in the development of DCM, and vild demonstrates significant potential for clinical application in prevention of DCM.

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