Metformin improves endothelial function in aortic tissue and microvascular endothelial cells subjected to diabetic hyperglycaemic conditions

Ghosh, Suparna; Lakshmanan, Arun Prasath; Hwang, Mu Ji; Kubba, Haidar; Mushannen, Ahmed; Triggle, Chris R.; Ding, Hong

doi:10.1016/j.bcp.2015.10.008

Cited by 41 publications

(39 citation statements)

References 39 publications

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“…In comparison to the nondiabetic WT mice, NO production was significantly decreased in the diabetic control mice (Figure A). Given that the phosphorylation of eNOS at Ser1177 is a critical regulatory process for NO generation, the phosphorylation status of eNOS was therefore evaluated herein. As expected, the phosphorylation levels of eNOS were significantly reduced in the diabetic control group (Figure B), consistent with the altered NO production.…”

Section: Resultsmentioning

confidence: 99%

Vildagliptin improves high glucose‐induced endothelial mitochondrial dysfunction via inhibiting mitochondrial fission

Liu

Xiang

Zhao

et al. 2018

J Cellular Molecular Medi

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The dipeptidyl peptidase 4 inhibitor vildagliptin (VLD), a widely used anti‐diabetic drug, exerts favourable effects on vascular endothelium in diabetes. We determined for the first time the improving effects of VLD on mitochondrial dysfunction in diabetic mice and human umbilical vein endothelial cells (HUVECs) cultured under hyperglycaemic conditions, and further explored the mechanism behind the anti‐diabetic activity. Mitochondrial ROS (mtROS) production was detected by fluorescent microscope and flow cytometry. Mitochondrial DNA damage and ATP synthesis were analysed by real time PCR and ATPlite assay, respectively. Mitochondrial network stained with MitoTracker Red to identify mitochondrial fragmentation was visualized under confocal microscopy. The expression levels of dynamin‐related proteins (Drp1 and Fis1) were determined by immunoblotting. We found that VLD significantly reduced mtROS production and mitochondrial DNA damage, but enhanced ATP synthesis in endothelium under diabetic conditions. Moreover, VLD reduced the expression of Drp1 and Fis1, blocked Drp1 translocation into mitochondria, and blunted mitochondrial fragmentation induced by hyperglycaemia. As a result, mitochondrial dysfunction was alleviated and mitochondrial morphology was restored by VLD. Additionally, VLD promoted the phosphorylation of AMPK and its target acetyl‐CoA carboxylase in the setting of high glucose, and AMPK activation led to a decreased expression and activation of Drp1. In conclusion, VLD improves endothelial mitochondrial dysfunction in diabetes, possibly through inhibiting Drp1‐mediated mitochondrial fission in an AMPK‐dependent manner.

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Section: Resultsmentioning

confidence: 99%

Vildagliptin improves high glucose‐induced endothelial mitochondrial dysfunction via inhibiting mitochondrial fission

Liu

Xiang

Zhao

et al. 2018

J Cellular Molecular Medi

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“…The protective effects of adiponectin on cardiovascular diseases are expected to be partially mediated by the activation of AMPK signaling [32]. Metformin improves diabetic endothelial function in association with AMPK activation [33]. AMPK/eNOS pathway is responsible for the protective role of ciglitazone in ox-LDL-induced endothelial cells [34].…”

Section: Discussionmentioning

confidence: 99%

C1q/TNF-Related Protein-9 Ameliorates Ox-LDL-Induced Endothelial Dysfunction via PGC-1α/AMPK-Mediated Antioxidant Enzyme Induction

Sun

Zhu

Zhou

et al. 2017

IJMS

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Oxidized low-density lipoprotein (ox-LDL) accumulation is one of the critical determinants in endothelial dysfunction in many cardiovascular diseases such as atherosclerosis. C1q/TNF-related protein 9 (CTRP9) is identified to be an adipocytokine with cardioprotective properties. However, the potential roles of CTRP9 in endothelial function remain largely elusive. In the present study, the effects of CTRP9 on the proliferation, apoptosis, migration, angiogenesis, nitric oxide (NO) production and oxidative stress in human umbilical vein endothelial cells (HUVECs) exposed to ox-LDL were investigated. We observed that treatment with ox-LDL inhibited the proliferation, migration, angiogenesis and the generation of NO, while stimulated the apoptosis and reactive oxygen species (ROS) production in HUVECs. Incubation of HUVECs with CTRP9 rescued ox-LDL-induced endothelial injury. CTRP9 treatment reversed ox-LDL-evoked decreases in antioxidant enzymes including heme oxygenase-1 (HO-1), nicotinamide adenine dinucleotide phosphate (NAD(P)H) dehydrogenase quinone 1, and glutamate-cysteine ligase (GCL), as well as endothelial nitric oxide synthase (eNOS). Furthermore, CTRP9 induced activation of peroxisome proliferator-activated receptor γ co-activator 1α (PGC1-α) and phosphorylation of adenosine monophosphate-activated protein kinase (AMPK). Of interest, AMPK inhibition or PGC1-α silencing abolished CTRP9-mediated antioxidant enzymes levels, eNOS expressions, and endothelial protective effects. Collectively, we provided the first evidence that CTRP9 attenuated ox-LDL-induced endothelial injury by antioxidant enzyme inductions dependent on PGC-1α/AMPK activation.

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“…For example, it has been shown that MET reduces lipopolysaccharide-induced proinflammatory responses in monocyes and macrophages [2], down-regulates Th17 cells in Rheumatoid Arthritis patients [3], decreases TNF-α receptor signaling and NF-kB activation in endothelial cells [4,5] and smooth muscle cells [6], and inhibits intestinal inflammation and colitis-associated colon cancer in intestinal epithelial cells [7]. MET has also been suggested to have cardioprotective effects through its reduction of inflammation, improvement of lipid profiles [8] and endothelial cell function [9], and retardation of the process of coronary artery calcification [10]. …”

Section: Introductionmentioning

confidence: 99%

Metformin improves in vivo and in vitro B cell function in individuals with obesity and Type-2 Diabetes

Diaz

Romero

Vazquez

et al. 2017

Vaccine

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Metformin (MET), the first-line medication for Type-2 Diabetes (T2D), has been shown to reduce chronic inflammation indirectly through reduction of hyperglycemia, or directly acting as anti-inflammatory drug. The effects of MET on B lymphocytes is uncharacterized. In the present study, we measured in vivo and in vitro influenza vaccine responses in 2 groups of T2D patients: recently diagnosed but not taking anti-diabetic drugs, and patients taking MET. Results show that B cell function and vaccine responses, hampered by obesity and T2D, are recovered by MET. Moreover, MET used in vitro to stimulate B cells from recently diagnosed T2D patients is also able to reduce B cell-intrinsic inflammation and increase antibody responses, similar to what we have seen in B cells from patients taking MET, who show increased responses to the influenza vaccine in vivo. These results are the first to show an effect of MET on B cells.

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Metformin improves endothelial function in aortic tissue and microvascular endothelial cells subjected to diabetic hyperglycaemic conditions

Cited by 41 publications

References 39 publications

Vildagliptin improves high glucose‐induced endothelial mitochondrial dysfunction via inhibiting mitochondrial fission

Vildagliptin improves high glucose‐induced endothelial mitochondrial dysfunction via inhibiting mitochondrial fission

C1q/TNF-Related Protein-9 Ameliorates Ox-LDL-Induced Endothelial Dysfunction via PGC-1α/AMPK-Mediated Antioxidant Enzyme Induction

Metformin improves in vivo and in vitro B cell function in individuals with obesity and Type-2 Diabetes

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