Metformin and liraglutide ameliorate high glucose-induced oxidative stress via inhibition of PKC-NAD(P)H oxidase pathway in human aortic endothelial cells

Batchuluun, Battsetseg; Inoguchi, Toyoshi; Sonoda, Noriyuki; Sasaki, Satoshi; Inoue, Tomoaki; Fujimura, Yoshinori; Miura, Daisuke; Takayanagi, Ryoichi

doi:10.1016/j.atherosclerosis.2013.10.025

Cited by 135 publications

(114 citation statements)

References 42 publications

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“…8) Liraglutide, a glucagon-like peptide-1 analogue, has been found to inhibit oxidative stress and inflammatory response in the endothelial cells, heart and brain. 19,20,22,23) Results obtained from the present study contribute to further understanding of the mechanisms whereby liraglutide exerts a protective effect against high fat and high cholesterol diet induced hepatic steatosis, insulin resistance and liver dysfunction. Administration of liraglutide effectively alleviated hepatic oxidative stress and inflammatory response.…”

Section: Discussionmentioning

confidence: 94%

“…[16][17][18] It has been reported that liraglutide reduces tumor necrosis factor (TNF)-α or high glucose induced oxidative stress and inflammatory response in human endothelial cells. 19,20) Inhibition of protein kinase C (PKC) translocation, reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and nuclear factor (NF)-κB activation may contribute to the anti-oxidative and anti-inflammatory effects of liraglutide. 19,20) Recently, liraglutide has been reported to reduce the level of plasma reactive oxygen metabolites, an indicator of oxidative stress, in patients with type 2 diabetes.…”

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confidence: 99%

“…19,20) Inhibition of protein kinase C (PKC) translocation, reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and nuclear factor (NF)-κB activation may contribute to the anti-oxidative and anti-inflammatory effects of liraglutide. 19,20) Recently, liraglutide has been reported to reduce the level of plasma reactive oxygen metabolites, an indicator of oxidative stress, in patients with type 2 diabetes. 21) In addition, the anti-inflammatory effect of liraglutide has been demonstrated in the heart of mice with diabetes and the brain of mice with Alzheimer's disease.…”

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confidence: 99%

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The Glucagon-Like Peptide-1 Analogue Liraglutide Inhibits Oxidative Stress and Inflammatory Response in the Liver of Rats with Diet-Induced Non-alcoholic Fatty Liver Disease

Gao

Zeng

Zhang

et al. 2015

Biological & Pharmaceutical Bulletin

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Liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, has been demonstrated to reduce hepatic steatosis. However, the mechanism of the lipid-lowering effect of liraglutide in the liver remains unclear. The aim of the present study was to investigate the beneficial effect of liraglutide on diet-induced non-alcoholic fatty liver disease (NAFLD) and the underlying mechanism in rats. NAFLD was induced in Sprague-Dawley rats by feeding a high fat and high cholesterol (HFHC) diet. Liraglutide (0.6 mg/kg body weight/d) was injected intraperitoneally to the rats subjected to HFHC diet four weeks before sacrificing the animals. Body and liver weight, fasting blood glucose (FBG), fasting insulin, serum aminotransferase (ALT) and lipid accumulation in the liver were determined. Markers of oxidative stress, such as malondialdehyde (MDA), free fatty acid (FFAs), superoxide dismutase (SOD), and pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) were detected by colorimetric detection or enzyme-linked immunosorbent assay (ELISA). Serum and hepatic adiponectin were measured by ELISA. The expression of c-Jun N-terminal kinase-1 (JNK-1) and phosphorylated JNK-1 were examined by Western blotting. Liraglutide improved insulin resistance, decreased hepatic steatosis and reversed liver dysfunction. The hepatic levels of MDA, FFAs, and TNF-α were significantly decreased versus controls. Meanwhile, administration of liraglutide significantly increased SOD and adiponectin levels in the liver and inhibited the expression of JNK-1 and phosphorylated JNK-1 versus control rats. Liraglutide exerted anti-oxidative and anti-inflammatory effects in the liver and consequently reversed hepatic steatosis and insulin resistance. Such effects might be mediated by the elevation of adiponectin levels and the inactivation of JNK-1.

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Section: Discussionmentioning

confidence: 94%

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confidence: 99%

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confidence: 99%

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The Glucagon-Like Peptide-1 Analogue Liraglutide Inhibits Oxidative Stress and Inflammatory Response in the Liver of Rats with Diet-Induced Non-alcoholic Fatty Liver Disease

Gao

Zeng

Zhang

et al. 2015

Biological & Pharmaceutical Bulletin

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“…It therefore shows a vasoprotective effect. [25][26][27] It is thought that the vasoprotective effects of the therapeutic agents like, metformin 24 , thiazolidinediones and statins also occur via the AMPK activation. 21 AMPK activation causes the NO-mediated relaxation in the spontaneously hypertensive rats.…”

Section: Adenosine Monophosphate-activated Protein Kinase Pathwaymentioning

confidence: 99%

“…23 Antidiabetic agents, such as, metformin 24 , thiazolidinediones, glukagon like peptid-1 agonists, dipeptidyl peptidase-4 inhibitors, statins, adiponectin and the leptin hormone increase the AMPK activation. 25,26 Experimentally, 5-aminoimidazole-4-carboxamide ribonucleoside is used for the AMPK activation 24 , whereas the dorsomorphine (compound C) is used for the inhibition.…”

Section: Adenosine Monophosphate-activated Protein Kinase Pathwaymentioning

confidence: 99%

Contribution of Rho-kinase and Adenosine Monophosphate-Activated Protein Kinase Signaling Pathways to Endothelium-Derived Contracting Factors Responses

Balcilar

Özakça

Altan

2017

tjps

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Vascular tonus is controlled by endothelium-derived relaxing factor (EDRF), endothelium-derived hyperpolarizing factor (EDHF) and endotheliumderived contracting factor (EDCF) under physiological circumstances. In pathological conditions, impairment of endothelium-derived relaxation can be caused by both decrease in EDRF release and increase in EDCF release. The increase in EDCF is observed with diseases such as hypertension and diabetes. The contribution of Rho-kinase and activated protein kinase (AMPK), which have opposite effects, to the increased EDCF responses was investigated. Rho-kinases are the effectors of Rho which is one of the small guanosine triphosphate-binding proteins. They increase cytosolic Ca +2 concentration and cause vascular smooth muscle to contract, keeping myosin light chain (MLC) in phosphorylated state by affecting myosin phosphatase target subunit which dephosphorylates the MLC. The activities of Rho-kinases increase with the increase of EDCF function. AMPK is the energy sensor of the cell. It provides a vasculoprotective effect by causing endothelium-dependent and endothelium-independent relaxation in smooth muscle. In contrast to Rho-kinase pathway activity, AMPK pathway activity decreases with diseases in which the EDCF function increases. In cases such as diabetes and hypertension that endothelial function impairs toward vasocontraction, it is considered that evaluating Rho-kinase and AMPK pathways which mediate contraction and relaxation in vascular smooth muscle respectively, would provide clues on choosing therapeutic target for pathologies in which endothelial dysfunction is observed. ÖZFizyolojik koşullarda vasküler tonus endotel kaynaklı rahatlatıcı faktörü (EDRF), endotel kaynaklı hiperpolarizasyon faktörü (EDHF) ve endotel kaynaklı kasılma faktörü (EDCF) tarafından kontrol edilmektedir. Patolojik durumlarda endotel kaynaklı gevşemenin azalması, EDRF üretimindeki azalmaya bağlı olabileceği gibi EDCF düzeyinin artmasına da bağlı olabilmektedir. EDCF hipertansiyon, diyabet gibi hastalıklarda artmaktadır. Diyabet, hipertansiyon gibi patolojik koşullarda artan EDCF yanıtına birbirine ters etki yapan Rho-kinaz ve aktive protein kinaz (AMPK) yolaklarının katkısı olabileceği düşünülmektedir. Rho-kinazlar küçük guanozin trifosfat-bağlı proteinlerden biri olan Rho'nun efektörüdür. Rho-kinazlar hafif zincir miyozini (MLC) defosforile eden miyozin fosfataz hedef altbirimine etki ederek MLC'nin fosforile halde kalmasının sağlayarak sitozolik Ca +2 konsantrasyonu artırır ve vasküler düz kasın kasılmasına neden olurlar. Rho-kinazların aktivitesi EDCF yanıtlarının arttığı hipertansiyon, kalp yetmezliği ve diyabet gibi hastalıklarda artmaktadır. AMPK ise hücrenin enerji sensörü olarak düşünülmektedir. Vasküler düz kasta endotel bağımlı ve bağımsız gevşemeyi sağlayarak vasküloprotektif etki sağlamaktadır. AMPK'nin aktivitesi Rho-kinaz yolağının aktivitesinin tersine EDCF fonksiyonunun arttığı hipertansiyon ve diyabet gibi hastalıklarda azalmaktadır. Endotel fonksiyonunun vazokonstriksiyon y...

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Glycogen at the Crossroad of Stress Resistance, Energy Maintenance, and Pathophysiology of Aging

Gusarov

Nudler

2018

BioEssays

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Glycogen is synthesized and stored to maintain postprandial blood glucose homeostasis and to ensure an uninterrupted energy supply between meals. Although the regulation of glycogen turnover has been well studied, the effects of glycogen on aging and disease development have been largely unexplored. In Caenorhabditis elegans fed a high sugar diet, glycogen potentiates resistance to oxidants, but paradoxically, shortens lifespan. Depletion of glycogen by oxidants or inhibition of glycogen synthesis extends the lifespan of worms by an AMPK-dependent mechanism. Thus, glycogen is not merely an inert storage molecule, but also an active regulator of energy balance and aging. Its depletion by oxidants may be beneficial in the treatment of hyperglycemia and glycogen-related diseases.

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Metformin and liraglutide ameliorate high glucose-induced oxidative stress via inhibition of PKC-NAD(P)H oxidase pathway in human aortic endothelial cells

Abstract: Metformin and liraglutide ameliorate high glucose-induced oxidative stress by inhibiting PKC-NAD(P)H oxidase pathway. A combination of these two drugs provides augmented protective effects, suggesting the clinical usefulness in prevention of diabetic vascular complications.

Cited by 135 publications

References 42 publications

The Glucagon-Like Peptide-1 Analogue Liraglutide Inhibits Oxidative Stress and Inflammatory Response in the Liver of Rats with Diet-Induced Non-alcoholic Fatty Liver Disease

The Glucagon-Like Peptide-1 Analogue Liraglutide Inhibits Oxidative Stress and Inflammatory Response in the Liver of Rats with Diet-Induced Non-alcoholic Fatty Liver Disease

Contribution of Rho-kinase and Adenosine Monophosphate-Activated Protein Kinase Signaling Pathways to Endothelium-Derived Contracting Factors Responses

Glycogen at the Crossroad of Stress Resistance, Energy Maintenance, and Pathophysiology of Aging

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