Effects of glucagon-like peptide-1 on advanced glycation endproduct-induced aortic endothelial dysfunction in streptozotocin-induced diabetic rats: possible roles of Rho kinase- and AMP kinase-mediated nuclear factor κB signaling pathways

Advances in our understanding of diabetes in human patients and experimental models indicate that a number of mechanisms may contribute to sensory nerve damage in diabetic polyneuropathy (DPN). In addition to oxidative stress, hyperglycemia and hyperlipidemia, recent research in pain, advanced glycation endproduct (AGE), and proteomics specify a contributory role for altered neuronal calcium homeostasis in DPN. Technology advances indicate neuronal energy balance and mitochondrial biogenesis, fission, and fusion are additional potential mechanisms. The effects of dysregulation or loss of insulin signaling and the effects of glucagon-like peptide-1 (GLP-1) and its receptor (GLP-1R) are also implicated.

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Glucagon Like Peptide-1 (GLP-1) Modulates OVA-Induced Airway Inflammation and Mucus Secretion Involving a Protein Kinase A (PKA)-Dependent Nuclear Factor-κB (NF-κB) Signaling Pathway in Mice

International Journal of Molecular Sciences ◽

10.3390/ijms160920195 ◽

2015 ◽

Vol 16 (9) ◽

pp. 20195-20211 ◽

Cited By ~ 28

Author(s):

Tao Zhu ◽

Xiao-ling Wu ◽

Wei Zhang ◽

Min Xiao

Keyword(s):

Protein Kinase ◽

Protein Kinase A ◽

Airway Inflammation ◽

Signaling Pathway ◽

Nuclear Factor Κb ◽

Mucus Secretion ◽

Nuclear Factor ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Kinase A

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A glucagon-like peptide-1 analog, liraglutide, ameliorates endothelial dysfunction through miRNAs to inhibit apoptosis in rats

PeerJ ◽

10.7717/peerj.6567 ◽

2019 ◽

Vol 7 ◽

pp. e6567 ◽

Cited By ~ 4

Author(s):

Qian Zhang ◽

Xinhua Xiao ◽

Jia Zheng ◽

Ming Li

Keyword(s):

Endothelial Dysfunction ◽

Endothelial Function ◽

Cell Function ◽

Diabetic Rats ◽

Pten Expression ◽

Endothelial Cell Function ◽

Differentially Expressed Mirnas ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Background and Aims Many studies have revealed that glucagon-like peptide-1 has vasoprotective effects. In this study, we investigated whether liraglutide suppressed endothelial dysfunction and explored the mechanism involved. Methods Experimental diabetes was induced through combined high-fat diet administration and intraperitoneal streptozotocin injections. Rats were randomly divided into the following four groups: control, diabetes, diabetes + a low liraglutide dose (0.2 mg/kg/d), and diabetes + a high liraglutide dose (0.4 mg/kg/d). Endothelial function and metabolic parameters were measured after 8 weeks of treatment. miRNA arrays were analyzed to identify the differentially expressed miRNAs. Results We found that liraglutide significantly improved aortic endothelial function in diabetic rats. Liraglutide inhibited miR-93-5p, miR-181a-5p and miR-34a-5p expression, and activated miR-26a-5p expression. miRNA mimic transfection experiments indicated negative relationships between miR-93-5p, miR-181a-5p, miR-34a-5p, and miR-26a-5p and Sirt1, Creb, Bcl-2, and Pten expression, respectively. Moreover, liraglutide increased Sirt1, Creb, and Bcl-2 expression levels and reduced Pten expression level. Conclusion Our results demonstrate the role of key miRNAs in the liraglutide-mediated regulation of endothelial cell function in diabetic rats.

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Simvastatin Improves Cardiac Hypertrophy in Diabetic Rats by Attenuation of Oxidative Stress and Inflammation Induced by Calpain-1-Mediated Activation of Nuclear Factor-κB (NF-κB)

Medical Science Monitor ◽

10.12659/msm.913244 ◽

2019 ◽

Vol 25 ◽

pp. 1232-1241 ◽

Cited By ~ 4

Author(s):

QianQian Han ◽

QianQian Liu ◽

Hui Zhang ◽

Meili Lu ◽

Hongxin Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Cardiac Hypertrophy ◽

Nuclear Factor Κb ◽

Diabetic Rats ◽

Nuclear Factor

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Effect of Glucagon-Like Peptide-1(7–36) and Exendin-4 on the Vascular Reactivity in Streptozotocin/Nicotinamide-Induced Diabetic Rats

Pharmacology ◽

10.1159/000084277 ◽

2005 ◽

Vol 74 (3) ◽

pp. 119-126 ◽

Cited By ~ 37

Author(s):

Sibel Özyazgan ◽

Nilüfer Kutluata ◽

Selim Afşar ◽

Şule Beyhan Özdaş ◽

Ahmet Gökhan Akkan

Keyword(s):

Vascular Reactivity ◽

Diabetic Rats ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

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Oxidative Stress-Dependent Impairment of Cardiac-Specific Transcription Factors in Experimental Diabetes

Endocrinology ◽

10.1210/en.2006-0728 ◽

2006 ◽

Vol 147 (12) ◽

pp. 5967-5974 ◽

Cited By ~ 73

Author(s):

Manuela Aragno ◽

Raffaella Mastrocola ◽

Claudio Medana ◽

Maria Graziella Catalano ◽

Ilenia Vercellinatto ◽

...

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Left Ventricle ◽

Nuclear Factor Κb ◽

Diabetic Rats ◽

Nuclear Factor ◽

Downstream Signaling ◽

Zdf Rats ◽

Myogenic Factors ◽

Age Receptors

Oxidative stress plays a key role in the pathogenesis of diabetic cardiomyopathy, which is characterized by myocyte loss and fibrosis, finally resulting in heart failure. The study looked at the downstream signaling whereby oxidative stress leads to reduced myocardial contractility in the left ventricle of diabetic rats and the effects of dehydroepiandrosterone (DHEA), which production is suppressed in the failing heart and prevents the oxidative damage induced by hyperglycemia in several experimental models. DHEA was given orally at a dose of 4 mg/rat per day for 21 d to rats with streptozotocin (STZ)-induced diabetes and genetic diabetic-fatty (ZDF) rats. Oxidative balance, advanced glycated end products (AGEs) and AGE receptors, cardiac myogenic factors, and myosin heavy-chain gene expression were determined in the left ventricle of treated and untreated STZ-diabetic rats and ZDF rats. Oxidative stress induced by chronic hyperglycemia increased AGE and AGE receptors and led to activation of the pleoitropic transcription factor nuclear factor-κB. Nuclear factor-κB activation triggered a cascade of signaling, which finally led to the switch in the cardiac myosin heavy-chain (MHC) gene expression from the α-MHC isoform to the β-MHC isoform. DHEA treatment, by preventing the activation of the oxidative pathways induced by hyperglycemia, counteracted the enhanced AGE receptor activation in the heart of STZ-diabetic rats and ZDF rats and normalized downstream signaling, thus avoiding impairment of the cardiac myogenic factors, heart autonomic nervous system and neural crest derivatives (HAND) and myogenic enhancer factor-2, and the switch in MHC gene expression, which are the early events in diabetic cardiomyopathy.

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