Liraglutide prevents β-cell apoptosis via inactivation of NOX2 and its related signaling pathway

Ding, Min; Fang, Qianhua; Cui, Yuantao; Shen, Qiling; Liu, Qian; Wang, Penghua; Yu, Di; Li, Chunjun

doi:10.1016/j.jdiacomp.2018.12.013

Cited by 30 publications

(24 citation statements)

References 44 publications

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“…As widely known, the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial, published in 2016, reported that liraglutide significantly decreased the composite of the occurrence of nonfatal myocardial infarction, nonfatal stroke or CV death as well as all-cause mortality and the composite outcome of retinal or renal events in T2DM patients [ 42 ]. Furthermore, liraglutide exerts anti-oxidative, anti-apoptotic and anti-inflammatory properties [ 43 , 44 ], and these effects could be mediated by its impact on miRNA levels [ 29 , 45 , 46 ] which is in accordance with our findings. Furthermore, it seems that liraglutide may protect the myocardium against ischemia/reperfusion injury, possibly through reducing cardiomyocyte apoptosis and oxidation [ 47 ].…”

Section: Discussionsupporting

confidence: 91%

Liraglutide Increases Serum Levels of MicroRNA-27b, -130a and -210 in Patients with Type 2 Diabetes Mellitus: A Novel Epigenetic Effect

et al. 2020

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Liraglutide has shown favourable effects on several cardiometabolic risk factors, beyond glucose control. MicroRNAs (miRNAs) regulate gene expression, resulting in post-transcriptional modifications of cell response and function. Specific miRNAs, including miRNA-27b, miRNA-130a, and miRNA-210, play a role in cardiometabolic disease. We aimed to determine the effect of liraglutide on the serum levels of miRNA-27b, miRNA-130a and miRNA-210. Twenty-five subjects with type-2 diabetes mellitus (T2DM), naïve to incretin-based therapy, were treated with liraglutide (1.2 mg/day as an add-on to metformin) for 4 months. miRNAs were quantified using real-time polymerase chain reaction. After liraglutide treatment, we found significant reductions in fasting glucose (from 9.8 ± 5.3 to 6.7 ± 1.6 mmol/L, p = 0.0042), glycosylated haemoglobin (HbA1c) (from 8.1 ± 0.8 to 6.6 ± 1.0%, p = 0.0008), total cholesterol (from 5.0 ± 1.0 to 4.0 ± 0.7 mmol/L, p = 0.0011), triglycerides (from 1.9 ± 1.0 to 1.5 ± 0.8 mmol/L, p = 0.0104) and low-density lipoprotein cholesterol (from 2.9 ± 1.2 to 2.2 ± 0.6 mmol/L, p = 0.0125), while the serum levels of miRNA-27b, miRNA-130a and miRNA-210a were significantly increased (median (interquartile range, IQR) changes: 1.73 (7.12) (p = 0.0401), 1.91 (3.64) (p = 0.0401) and 2.09 (11.0) (p = 0.0486), respectively). Since the changes in miRNAs were independent of changes in all the metabolic parameters investigated, liraglutide seems to exert a direct epigenetic effect in T2DM patients, regulating microRNAs involved in the maintenance of endothelial cell homeostasis. These changes might be implicated in liraglutide’s benefits and may represent useful targets for cardiometabolic management.

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Section: Discussionsupporting

confidence: 91%

Liraglutide Increases Serum Levels of MicroRNA-27b, -130a and -210 in Patients with Type 2 Diabetes Mellitus: A Novel Epigenetic Effect

et al. 2020

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“…Liraglutide protects against beta cell apoptosis, [ 11 , 12 ] suggesting its suitability for treating MODY 5 patients who show partial defects in pancreatic beta cells. Additionally, reduced HNF1B expression in the liver causes insulin resistance via impaired insulin signaling, accelerates gluconeogenesis, and increases dipeptidyl peptidase-4 level.…”

Section: Discussionmentioning

confidence: 99%

“…The current study describes the first case of MODY 5 treated with the GLP-1RA, liraglutide, which exerted protective effects against pancreatic beta cell dysfunction. [ 11 , 12 ]…”

Section: Introductionmentioning

confidence: 99%

Maturity-Onset diabetes of the young type 5 treated with the glucagon-like peptide-1 receptor agonist

et al. 2020

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Rationale: Maturity-onset diabetes of the young type 5 (MODY 5) is a form of monogenic diabetes that is often accompanied by pancreatic dysfunction. To date, no cases of MODY 5 treated with glucagon-like peptide-1 receptor agonist (GLP-1RA) have been reported. We present the first case of MODY 5 treated with GLP-1RA. Patient concerns: A 17-year-old woman, with a history of being operated for congenital ileal atresia at birth, was admitted to our hospital due to hyperglycemia. She had been clinically diagnosed with type 1 diabetes 1 month prior, and administered 14 units of insulin glargine 300 U/mL per day. Diagnosis: She had hypopotassemia, hypomagnesaemia, pancreatic body, and tail defects, multiple renal cysts, and a family history of diabetes, and urogenital anomaly. Genetic testing revealed heterozygous deletion of hepatocyte nuclear transcription factor-1 beta, leading to the diagnosis of MODY 5. Interventions: The patient was treated with multiple daily insulin injections for 9 days (22 units/d) before administration of GLP-1RA, and then liraglutide was initiated. Outcomes: Liraglutide treatment (0.6 mg/d) alone maintained the patient's glycated hemoglobin level below 7.0% for at least 12 months after discharge. A higher dose, 0.9 mg/d, of liraglutide was not tolerated by the patient due to nausea. Serum levels of C-peptide immunoreactivity were 1.15 ng/mL and 1.91 ng/mL, respectively, after 6 and 12 months of liraglutide therapy. Lessons: GLP-1RA might be effective at regulating glucose metabolism by utilizing residual pancreatic endocrine function in patients with MODY 5. Imaging and genetic screening were helpful in the diagnosis of MODY 5.

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“…Many pathways have been identified to play a role in the prevention of apoptosis that will not be described in detail here. Among those pathways recently identified are SAD-A mediated phosphorylation of Bad (S155) [220], upregulation of BiP and JunB [221], increased Akt signaling and increased SIRT1 and α-Klotho [222], restoration of Pdx-1 expression [223], AMPK/mTOR/p70 S6K [224], and activation of the NOX2 pathway [225]. Both GLP-1 and GIP have also been shown to act through K V 2.1 to enhance beta cell survival [226].…”

Section: D: Cell Viabilitymentioning

confidence: 99%

New Insights into Beta-Cell GLP-1 Receptor and cAMP Signaling

Tomás

Jones

Leech

2020

Journal of Molecular Biology

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Liraglutide prevents β-cell apoptosis via inactivation of NOX2 and its related signaling pathway

Cited by 30 publications

References 44 publications

Liraglutide Increases Serum Levels of MicroRNA-27b, -130a and -210 in Patients with Type 2 Diabetes Mellitus: A Novel Epigenetic Effect

Liraglutide Increases Serum Levels of MicroRNA-27b, -130a and -210 in Patients with Type 2 Diabetes Mellitus: A Novel Epigenetic Effect

Maturity-Onset diabetes of the young type 5 treated with the glucagon-like peptide-1 receptor agonist

New Insights into Beta-Cell GLP-1 Receptor and cAMP Signaling

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