Liraglutide and Semaglutide Attenuate Inflammatory Cytokines Interferon-Gamma, Tumor Necrosis Factor-Alpha, and Interleukin-6: Possible Mechanism of Decreasing Cardiovascular Risk in Diabetes Mellitus

Tan, Stanley Andrew; Tan, Linda G.

doi:10.1016/s0735-1097(19)32472-6

Cited by 4 publications

(4 citation statements)

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“…In the present study, co-treatment with either alogliptin or semaglutide ameliorated the coupled upregulation of NF-κB/TNF-α induced by DOX. These results are in accordance with other studies reporting the anti-inflammatory effects of GLP-1RA, semaglutide, in different models, such as obesity, multiple sclerosis, and diabetes ( Tan and Tan, 2019 ; Pan et al, 2023 ; Sadek et al, 2023 ), and the DPP-4 inhibitor, alogliptin, in lipopolysaccharide-induced neuroinflammation ( El-Sahar et al, 2021 ). It is also worth mentioning that alogliptin showed the protective effect against DOX-induced testicular dysfunction through decreasing oxidative stress, inflammation, and apoptosis ( Kabel, 2018 ).…”

Section: Discussionsupporting

confidence: 93%

Comparative effects of incretin-based therapy on doxorubicin-induced nephrotoxicity in rats: the role of SIRT1/Nrf2/NF-κB/TNF-α signaling pathways

Botros,

Matouk,

Amin

et al. 2024

Front. Pharmacol.

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Introduction: Nephrotoxicity represents a major complication of using doxorubicin (DOX) in the management of several types of cancers. Increased oxidative stress and the activation of inflammatory mediators play outstanding roles in the development of DOX-induced kidney damage. This study aimed to investigate whether the two pathways of incretin-based therapy, glucagon-like peptide-1 receptor agonist (presented as semaglutide, SEM) and dipeptidyl peptidase-4 inhibitor (presented as alogliptin, ALO), differentially protect against DOX-induced nephrotoxicity in rats and to clarify the underlying molecular mechanisms.Methods: Adult male rats were divided into six groups: control (received the vehicle), DOX (20 mg/kg, single I.P. on day 8), DOX + ALO (20 mg/kg/day, P.O. for 10 days), DOX + SEM (12 μg/kg/day, S.C. for 10 days), ALO-alone, and SEM-alone groups. At the end of the study, the animals were sacrificed and their kidney functions, oxidative stress, and inflammatory markers were assessed. Kidney sections were also subjected to histopathological examinations.Results: The co-treatment with either ALO or SEM manifested an improvement in the kidney functions, as evidenced by lower serum concentrations of creatinine, urea, and cystatin C compared to the DOX group. Lower levels of MDA, higher levels of GSH, and increased SOD activity were observed in either ALO- or SEM-treated groups than those observed in the DOX group. DOX administration resulted in decreased renal expressions of sirtuin 1 (SIRT1) and Nrf2 with increased NF-κB and TNF-α expressions, and these effects were ameliorated by treatment with either ALO or SEM.Discussion: Co-treatment with either ALO or SEM showed a renoprotective effect that was mediated by their antioxidant and anti-inflammatory effects via the SIRT1/Nrf2/NF-κB/TNF-α pathway. The fact that both pathways of the incretin-based therapy demonstrate an equally positive effect in alleviating DOX-induced renal damage is equally noteworthy.

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Section: Discussionsupporting

confidence: 93%

Comparative effects of incretin-based therapy on doxorubicin-induced nephrotoxicity in rats: the role of SIRT1/Nrf2/NF-κB/TNF-α signaling pathways

Botros,

Matouk,

Amin

et al. 2024

Front. Pharmacol.

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“…Microglia express receptors for GLP-1 [25], probably accounting for the anti-inflammatory effects of GLP-1 agonists: liraglutide caused significantly decreased levels of IFN-γ, TNF-α, and IL-6 [26]; and semaglutide led to reductions in CRP that were positively correlated with reductions in bodyweight, waist circumference, fasting plasma glucose, and fasting serum insulin [27,28].…”

Section: Glp-1 and Microgliamentioning

confidence: 99%

All GLP-1 Agonists Should, Theoretically, Cure Alzheimer’s Dementia but Dulaglutide Might Be More Effective Than the Others

Fessel

2024

JCM

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Addressing the dysfunctions of all brain cell types in Alzheimer’s disease (AD) should cure the dementia, an objective that might be achieved by GLP-1 agonist drugs, because receptors for GLP-1 are present in all of the main brain cell types, i.e., neurons, oligodendroglia, astroglia, microglia, endothelial cells and pericytes. This article describes the benefits provided to all of those brain cell types by GLP-1 agonist drugs. The article uses studies in humans, not rodents, to describe the effect of GLP-1 agonists upon cognition, because rodents’ brains differ from those of humans in so many ways that results from rodent studies may not be totally transferable to humans. Commercially available GLP-1 agonists have mostly shown either positive effects upon cognition or no effects. One important reason for no effects is a reduced rate of entering brain parenchyma. Dulaglutide has the greatest entry to brain, at 61.8%, among the available GLP-1 agonists, and seems to offer the best likelihood for cure of AD. Although there is only one study of cognition that used dulaglutide, it was randomized, placebo controlled, and very large; it involved 8828 participants and showed significant benefit to cognition. A clinical trial to test the hypothesis that dulaglutide may cure AD should have, as its primary outcome, a 30% greater cure rate of AD by dulaglutide than that achieved by an equipoise arm of, e.g., lithium plus memantine.

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“…29,37 Of particular interest, GLP-1R agonists have been shown to decrease inflammatory cytokines in animals 38 and humans. 37,39 Other medications for T2DM that have anti-inflammatory effects include dipeptidyl peptidase-4 (DPP-4) inhibitors which block the breakdown of GLP-1 and have been shown to regulate other coronaviruses, 40 and pioglitazone which is a thiazolidinedione. 23,41 We hypothesized that the use of GLP-1R agonists, DPP-4 inhibitors or pioglitazone within 6 months prior to the diagnosis of COVID-19 would reduce hospital admissions, respiratory complications, and mortality within 28 days following the diagnosis of COVID-19 in patients with T2DM.…”

Section: Introductionmentioning

confidence: 99%

“…GLP-1R agonists also have positive effects on body weight, BMI, blood pressure, and cholesterol ( 29 , 37 ). Of particular interest, GLP-1R agonists have been shown to decrease inflammatory cytokines in animals ( 38 ) and humans ( 37 , 39 ). Other medications for T2DM that have anti-inflammatory effects include DPP-4 inhibitors, which block the breakdown of GLP-1 and have been shown to regulate other coronaviruses ( 40 ), and pioglitazone, which is a TDZ ( 23 , 41 ).…”

Section: Introductionmentioning

confidence: 99%

Diabetes, Drug Treatment, and Mortality in COVID-19: A Multinational Retrospective Cohort Study

Nyland¹,

Raja-Khan²,

Bettermann³

et al. 2021

Diabetes

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Patients with type 2 diabetes mellitus (T2DM) are at increased risk of severe COVID-19 outcomes possibly due to dysregulated inflammatory responses. Glucose-regulating medications such as glucagon-like peptide-1 receptor (GLP-1R) agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and pioglitazone are known to have anti-inflammatory effects that may improve outcomes in patients with SARS-CoV-2 infection. In a multinational retrospective cohort study, we used the TriNetX COVID-19 Research Network of 56 large healthcare organizations to examine these medications in relation to the incidence of hospital admissions, respiratory complications, and mortality within 28 days following a COVID-19 diagnosis. After matching for age, sex, race, ethnicity, body mass index, and significant comorbidities, use of GLP-1R agonists and/or pioglitazone was associated with significant reductions in hospital admissions

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Liraglutide and Semaglutide Attenuate Inflammatory Cytokines Interferon-Gamma, Tumor Necrosis Factor-Alpha, and Interleukin-6: Possible Mechanism of Decreasing Cardiovascular Risk in Diabetes Mellitus

Cited by 4 publications

References 0 publications

Comparative effects of incretin-based therapy on doxorubicin-induced nephrotoxicity in rats: the role of SIRT1/Nrf2/NF-κB/TNF-α signaling pathways

Comparative effects of incretin-based therapy on doxorubicin-induced nephrotoxicity in rats: the role of SIRT1/Nrf2/NF-κB/TNF-α signaling pathways

All GLP-1 Agonists Should, Theoretically, Cure Alzheimer’s Dementia but Dulaglutide Might Be More Effective Than the Others

Diabetes, Drug Treatment, and Mortality in COVID-19: A Multinational Retrospective Cohort Study

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