Liraglutide protects palmitate-induced INS-1 cell injury by enhancing autophagy mediated via FoxO1

Li, Xiudan; He, Shanshan; Wan, Tingting; Li, Yanbo

doi:10.3892/mmr.2020.11786

Cited by 19 publications

(20 citation statements)

References 42 publications

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“…Interestingly, the ST2, ST3, and ST4 chemotypes were able to similarly protect INS-1E beta cells from the lipotoxic action due to prolonged exposure to the saturated fatty acid, palmitate. Indeed, palmitate reduced cell viability by 20–40%, confirming previous work with this model [ 39 , 50 , 51 ]. However, the presence of ST2, ST3, and ST4 prevented palmitate-induced beta-cell damage in INS-1E beta cells.…”

Section: Discussionsupporting

confidence: 88%

“…The main markers of lipotoxicity are ER stress and mitochondrial dysfunction. Palmitate triggers ER stress, affecting ER folding capacity and inducing overload of misfolded protein, and increase ROS production, causing mitochondrial dysfunction [ 3 – 5 , 8 , 39 , 40 , 43 , 47 , 50 , 51 , 53 ]. Of interest, our proteomic results showed that the ST3 extract regulates the expression of proteins related to ER and mitochondria.…”

Section: Discussionmentioning

confidence: 99%

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Protective effects of Stevia rebaudiana extracts on beta cells in lipotoxic conditions

et al. 2021

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Aims Stevia rebaudiana Bertoni leaf extracts have gained increasing attention for their potential protection against type 2 diabetes. In this study, we have evaluated the possible beneficial effects of Stevia rebaudiana leaf extracts on beta-cells exposed to lipotoxicity and explored some of the possible mechanisms involved. Methods Extracts, deriving from six different chemotypes (ST1 to ST6), were characterized in terms of steviol glycosides, total phenols, flavonoids, and antioxidant activity. INS-1E beta cells and human pancreatic islets were incubated 24 h with 0.5 mM palmitate with or without varying concentrations of extracts. Beta-cell/islet cell features were analyzed by MTT assay, activated caspase 3/7 measurement, and/or nucleosome quantification. In addition, the proteome of INS-1E cells was assessed by bi-dimensional electrophoresis (2-DE). Results The extracts differed in terms of antioxidant activity and stevioside content. As expected, 24 h exposure to palmitate resulted in a significant decrease of INS-1E cell metabolic activity, which was counteracted by all the Stevia extracts at 200 μg/ml. However, varying stevioside only concentrations were not able to protect palmitate-exposed cells. ST3 extract was also tested with human islets, showing an anti-apoptotic effect. Proteome analysis showed several changes in INS-1E beta-cells exposed to ST3, mainly at the endoplasmic reticulum and mitochondrial levels. Conclusions Stevia rebaudiana leaf extracts have beneficial effects on beta cells exposed to lipotoxicity; this effect does not seem to be mediated by stevioside alone (suggesting a major role of the leaf phytocomplex as a whole) and might be due to actions on the endoplasmic reticulum and the mitochondrion.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Protective effects of Stevia rebaudiana extracts on beta cells in lipotoxic conditions

et al. 2021

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“…In glucolipotoxic beta-cells (clonal INS-1E cells and human islets) that showed increased apoptosis, the number of autophagosomes was shown to be increased, demonstrating a blockade of the autophagic flux [56]. Interestingly, treatment of beta-cells and/or animals with exendin-4 [56] or liraglutide [153,[185][186][187] rescued lysosomal function and autophagic flux in both lipotoxic and glucolipotoxic conditions leading to a protective effect on beta-cells, and suggesting that stimulation of the autophagic flux by GLP-1 is critical for its protective effects [188].…”

Section: Glp-1ra Alleviates Beta-cell Apoptosis Induced By Diabetogenic Conditions or In T2dmentioning

confidence: 99%

“…The mechanisms underlying the impact of GLP-1RA on both autophagy and lysosomal function are not yet elucidated, but several pathways have been explored. It has been recently reported in INS-1 cells that liraglutide ameliorated the injury triggered by lipotoxic conditions through the upregulation of autophagy mediated by FoxO1 [187], or throughout the upregulation of mesencephalic astrocyte derived neurotrophic factor (MANF) in MIN6 cells [189], thus protecting cells from ER stress. It has also been reported that GLP-1 may protect beta-cells from glucotoxicity through enhancing autophagy by AMPK inhibition in INS-1 cells [190].…”

Section: Glp-1ra Alleviates Beta-cell Apoptosis Induced By Diabetogenic Conditions or In T2dmentioning

confidence: 99%

Mechanisms of Beta-Cell Apoptosis in Type 2 Diabetes-Prone Situations and Potential Protection by GLP-1-Based Therapies

Costes

Bertrand

Ravier

2021

IJMS

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Type 2 diabetes (T2D) is characterized by chronic hyperglycemia secondary to the decline of functional beta-cells and is usually accompanied by a reduced sensitivity to insulin. Whereas altered beta-cell function plays a key role in T2D onset, a decreased beta-cell mass was also reported to contribute to the pathophysiology of this metabolic disease. The decreased beta-cell mass in T2D is, at least in part, attributed to beta-cell apoptosis that is triggered by diabetogenic situations such as amyloid deposits, lipotoxicity and glucotoxicity. In this review, we discussed the molecular mechanisms involved in pancreatic beta-cell apoptosis under such diabetes-prone situations. Finally, we considered the molecular signaling pathways recruited by glucagon-like peptide-1-based therapies to potentially protect beta-cells from death under diabetogenic situations.

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“…Type 2 diabetes mellitus (T2DM) is another metabolic-related disease progressing exponentially. The T2DM hallmark is the development of insulin resistance, due to impaired response to the hormone or its reduced production by pancreatic β-cells ( Boland et al, 2017 ; Li et al, 2021 ), thereby resulting in high glucose levels, increased general oxidative stress, vascular problems, and serious secondary perturbations in the physiology and the metabolism of the body ( Chatterjee et al, 2017 ; Galicia-Garcia et al, 2020 ). In diabetic patients, lipid metabolism is modified, and the liver may accumulate fatty acids (FAs), which facilitates the establishment of NAFLD ( Sanyal, 2019 ; Kuchay et al, 2020 ).…”

Section: Homeostatic Dysfunctions In Non-alcoholic Fatty Liver Diseasementioning

confidence: 99%

Drosophila melanogaster: A Powerful Tiny Animal Model for the Study of Metabolic Hepatic Diseases

Moraes

Montagne

2021

Front. Physiol.

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Animal experimentation is limited by unethical procedures, time-consuming protocols, and high cost. Thus, the development of innovative approaches for disease treatment based on alternative models in a fast, safe, and economic manner is an important, yet challenging goal. In this paradigm, the fruit-fly Drosophila melanogaster has become a powerful model for biomedical research, considering its short life cycle and low-cost maintenance. In addition, biological processes are conserved and homologs of ∼75% of human disease-related genes are found in the fruit-fly. Therefore, this model has been used in innovative approaches to evaluate and validate the functional activities of candidate molecules identified via in vitro large-scale analyses, as putative agents to treat or reverse pathological conditions. In this context, Drosophila offers a powerful alternative to investigate the molecular aspects of liver diseases, since no effective therapies are available for those pathologies. Non-alcoholic fatty liver disease is the most common form of chronic hepatic dysfunctions, which may progress to the development of chronic hepatitis and ultimately to cirrhosis, thereby increasing the risk for hepatocellular carcinoma (HCC). This deleterious situation reinforces the use of the Drosophila model to accelerate functional research aimed at deciphering the mechanisms that sustain the disease. In this short review, we illustrate the relevance of using the fruit-fly to address aspects of liver pathologies to contribute to the biomedical area.

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Liraglutide protects palmitate-induced INS-1 cell injury by enhancing autophagy mediated via FoxO1

Cited by 19 publications

References 42 publications

Protective effects of Stevia rebaudiana extracts on beta cells in lipotoxic conditions

Protective effects of Stevia rebaudiana extracts on beta cells in lipotoxic conditions

Mechanisms of Beta-Cell Apoptosis in Type 2 Diabetes-Prone Situations and Potential Protection by GLP-1-Based Therapies

Drosophila melanogaster: A Powerful Tiny Animal Model for the Study of Metabolic Hepatic Diseases

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