Exendin-4 protects against high glucose-induced mitochondrial dysfunction and oxidative stress in SH-SY5Y neuroblastoma cells through GLP-1 receptor/Epac/Akt signaling

Pandey, Sudhir; Mangmool, Supachoke; Madreiter‐Sokolowski, Corina T.; Wichaiyo, Surasak; Luangmonkong, Theerut; Parichatikanond, Warisara

doi:10.1016/j.ejphar.2023.175896

Cited by 6 publications

(3 citation statements)

References 54 publications

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“…Taken together, these findings further supported the fact that GLP-1 receptor-mediated increases in beating rates occur by NO and cyclooxygenase products. Although previous studies have shown that GLP-1 receptor activation reduces the level of free radicals by increasing the SOD and CAT, [31][32][33] in this study, neither SOD nor CAT or SOD and CAT incubations altered the increases in beating rates induced by GLP-1 , GLP-1 (9-36) amide, exendin-4 (1-39), or sitagliptin. However, Green et al showed that GLP-1 causes significant concentration-dependent relaxation of isolated rat aorta through stimulation of cyclic adenosine monophosphate and subsequent opening of adenosine triphosphate-sensitive potassium channel (K ATP ) but not by NO, cyclooxygenase products, or hydrogen peroxide.…”

Section: Discussioncontrasting

confidence: 91%

Chronotropic Responses to GLP-1 Receptor Agonists and Sitagliptin in Atria from Diabetic Rats

Akcabag,

Aksoyalp,

Oner

et al. 2024

Journal of Cardiovascular Pharmacology

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Type 2 Diabetes Mellitus (T2DM) increases the risk of cardiovascular diseases. Therefore, elucidation of the cardiovascular effects of antidiabetics is crucial. Incretin-based therapies are increasingly used for T2DM treatment as monotherapy and in combination. We aimed to study the effects of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs) and sitagliptin on beating rates in isolated atria from diabetic rats. The chronotropic responses to GLP-1 RAs and sitagliptin as monotherapy and in combinations with metformin, pioglitazone, and glimepiride in isolated atria from control and diabetic rats were determined. GLP-1 (7-36), GLP-1 (9-36), and Exendin-4 (1-39) produced increases in beating rates in both control and diabetic rat atria. However, sitagliptin increased the beating frequency only in the diabetic group. Exendin (9-39), L-NAME, and indomethacin blocked responses to GLP-1 RAs but not the response to sitagliptin. Glibenclamide, 4-aminopyridine, apamin, charybdotoxin, superoxide dismutase, and catalase incubations did not change responses to GLP-1 RAs and sitagliptin. GLP-1 RAs increase beating rates in isolated rat atrium through GLP-1 receptor, nitric oxide, and cyclooxygenase pathways but not potassium channels and reactive oxygen radicals.

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Section: Discussioncontrasting

confidence: 91%

Chronotropic Responses to GLP-1 Receptor Agonists and Sitagliptin in Atria from Diabetic Rats

Akcabag,

Aksoyalp,

Oner

et al. 2024

Journal of Cardiovascular Pharmacology

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“…Pandey et al used high-glucose treatment in SH-SY5Y cells to mimic diabetic neuropathy and explored the effect of the GLP-1R agonist exendin-4 on diabetic neuropathy (48). The data showed that exendin-4 treatment elevated the levels of p-protein kinase B (Akt) and B-cell lymphoma 2 (Bcl-2) and suppressed the level of Bax, which indicated a lower level of cell apoptosis.…”

Section: In Vitro Evidencementioning

confidence: 99%

Glucagon-like peptide-1 receptor agonists for the management of diabetic peripheral neuropathy

Liu,

Wu,

Ren

2024

Front. Endocrinol.

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Diabetes mellitus is a prevalent chronic disease characterized by hyperglycemia. Diabetic peripheral neuropathy (DPN) is one of the complications of diabetes mellitus and is caused by neuron injury induced by hyperglycemic circumstances. The incidence of DPN varies among different countries and regions, ranging from nearly 20% to over 70%. Patients with DPN may encounter symmetric pain or discomfort of the extremes, leading to reduced quality of life and even amputation. The pharmacological management for painful DPN mainly includes antidepressants due to their analgesic effects. Nevertheless, effective therapies to impact the pathogenesis and progression of DPN are lacking. Glucagon-like peptide-1 receptor (GLP-1R) agonists show efficacy in controlling blood glucose and serve as a treatment modality for diabetes mellitus. In recent years, evidence has been proposed that GLP-1R agonists exert neuroprotective effects through modulating inflammation, oxidative stress, and mitochondrial dysfunction. On the other hand, clinical evidence on the potential of GLP-1R agonists for treating DPN is still controversial and limited. This narrative review summarizes the preclinical and clinical studies investigating the capacity of GLP-1R agonists as therapeutic agents for DPN.

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“…In this context, exendin-4 shielded SH-SY5Y neuroblastoma cells from mitochondrial dysfunction and oxidative stress triggered by high glucose levels. Consequently, it can be concluded that exendin-4 has the potential to serve as a therapeutic option for mitigating neuronal impairments and slowing down the development of diabetic neuropathies (Pandey et al, 2023). In addition, exendin-4 protected cultured rat hippocampal neurons against glutamate-triggered apoptosis and reversed excitotoxic neuronal damage (Perry et al, 2002).…”

Section: Neuroprotective Potential Of Exendin-4mentioning

confidence: 99%

Exendin‐4: A potential therapeutic strategy for Alzheimer's disease and Parkinson's disease

Verma,

Chaudhary,

Solanki

et al. 2023

Chem Biol Drug Des

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Neurodegenerative disorders, which affect millions worldwide, are marked by a steady decline of neurons that are selectively susceptible. Due to the complex pathological processes underlying neurodegeneration, at present, there is no viable therapy available for neurodegenerative disorders. Consequently, the establishment of a novel therapeutic approach for such conditions is a clinical void that remains. The potential significance of various peptides as neuroprotective interventions for neurodegenerative disorders is gaining increasing attention. In the past few years, there has been growing scientific interest in glucagon‐like peptide‐1 receptor agonists due to their claimed neuroprotective effects. Exendin‐4 is a glucagon‐like peptide‐1 receptor agonist that is known to possess anti‐diabetic effects and does not degrade for hours, making it a superior candidate for such disorders. Moreover, exendin‐4's neuroprotective effects have been reported in several preclinical studies. Exendin‐4's diverse therapeutic targets suggest its potential therapeutic uses in neurodegenerative ailments like Alzheimer's disease and Parkinson's disease and have garnered an increasing amount of attention. Given the substantial body of evidence supporting the neuroprotective potential of exendin‐4 in various research models, this article is dedicated to exploring the promising role of exendin‐4 as a therapeutic agent for the treatment and management of Alzheimer's disease and Parkinson's disease. This review draws insights from the findings of numerous preclinical and clinical studies to highlight the collective neuroprotective advantages of exendin‐4 and the potential mechanisms that underlie its neuroprotective effects.

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Exendin-4 protects against high glucose-induced mitochondrial dysfunction and oxidative stress in SH-SY5Y neuroblastoma cells through GLP-1 receptor/Epac/Akt signaling

Cited by 6 publications

References 54 publications

Chronotropic Responses to GLP-1 Receptor Agonists and Sitagliptin in Atria from Diabetic Rats

Chronotropic Responses to GLP-1 Receptor Agonists and Sitagliptin in Atria from Diabetic Rats

Glucagon-like peptide-1 receptor agonists for the management of diabetic peripheral neuropathy

Exendin‐4: A potential therapeutic strategy for Alzheimer's disease and Parkinson's disease

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