Caveolin-1 deficiency protects pancreatic β cells against palmitate-induced dysfunction and apoptosis

Zeng, Wen; Tang, Jiansong; Li, Haicheng; Xu, Haixia; Lu, Hongyun; Peng, Hangya; Lin, Chuwen; Gao, Rili; Lin, Shuo; Kh, Lin; Liu, Kunying; Jiang, Yan; Weng, Jianping

doi:10.1016/j.cellsig.2018.03.013

Cited by 21 publications

(14 citation statements)

References 55 publications

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“…Similar results were also observed in PA‐induced GLUTag cells. PA, a toxic long‐chain saturated fatty acid, has been shown to promote cellular ROS generation and activate the MAPKs signaling pathways induced to induce β cells apoptosis (Zeng et al, 2018). Besides, in this study, a decrease in ROS after receiving SAL treatment was also detected in different cell models of HepG2 treated with glucosamine and GLUTag treated with PA.…”

Section: Discussionmentioning

confidence: 99%

Retracted : Salidroside from Rhodiola wallichiana var. cholaensis reverses insulin resistance and stimulates the GLP‐1 secretion by alleviating ROS‐mediated activation of MAPKs signaling pathway and mitigating apoptosis

Yan

Nian

et al. 2020

J. Food Biochem.

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The present study was aimed to investigate the mechanisms of salidroside (SAL) from Rhodiola wallichiana var. cholaensis on hypoglycemic and oxidative stress responses. The palmitate (PA)-induced GLUTag cells model and the glucosamine-induced insulin resistance model in HepG2 cells were built. SAL led to the up-regulation of the serum glucagon-like peptide 1 (GLP-1) level by facilitating the SCFAs production, the promotion of GLP-1 synthesis by improving p38 MAPK phosphorylation and regulating insulin resistance. Moreover, the production of reactive oxygen species (ROS) and the expression of MAPKs were down-regulated. Furthermore, SAL was found to be able to inhibit PA-induced apoptosis that down-regulates cleaved caspase-3 and Bax expressions, while up-regulating Bcl-2 expression and up-regulates the Bcl-2/ Bax ratio in glucosamine induced insulin resistance model. Besides, SAL can also upregulate the mTOR/p70S6k signaling pathway in the PA-induced GLUTag cells model. Our data demonstrated that SAL could reverse insulin resistance and stimulates the GLP-1 secretion by alleviating ROS-mediated activation of MAPKs signaling pathway and mitigating apoptosis. Practical applications Our data showed that SAL could increase the GLP-1 level by stimulating the SCFAs production and p38 phosphorylation and facilitate the IR and GLP-1 synthesis by alleviating ROS-mediated activation of MAPKs signaling pathway and mitigating apoptosis. Furthermore, the SAL has also stimulated the mTOR/p70S6k signaling pathway in PA-induced GLUTag cells model. The results provided a possibility to employ SAL for diabetes treatment.

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Section: Discussionmentioning

confidence: 99%

Retracted : Salidroside from Rhodiola wallichiana var. cholaensis reverses insulin resistance and stimulates the GLP‐1 secretion by alleviating ROS‐mediated activation of MAPKs signaling pathway and mitigating apoptosis

Yan

Nian

et al. 2020

J. Food Biochem.

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“…Recently, the mechanisms associated with CAV1 silencing and β-cell homeostasis, survival, and insulin secretion have been revealed. Zeng et al found that in pan-creatic β-cells, lipotoxicity is moderated when CAV1 is depleted due to the activation of AKT (RAC-alpha serine threonine protein kinase) and ERK1/2 (extracellular-signalregulated kinase) signaling pathways, which in turn downregulate the expression of cell cycle arrest proteins and upregulate the expression of cell cycle activators [20].…”

Section: Role Of Caveolin-1 In Insulin Secretion and Development Of Dmentioning

confidence: 99%

Role of Caveolin-1 in Diabetes and Its Complications

Haddad

Madhoun

Nizam

et al. 2020

Oxidative Medicine and Cellular Longevity

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It is estimated that in 2017 there were 451 million people with diabetes worldwide. These figures are expected to increase to 693 million by 2045; thus, innovative preventative programs and treatments are a necessity to fight this escalating pandemic disorder. Caveolin-1 (CAV1), an integral membrane protein, is the principal component of caveolae in membranes and is involved in multiple cellular functions such as endocytosis, cholesterol homeostasis, signal transduction, and mechanoprotection. Previous studies demonstrated that CAV1 is critical for insulin receptor-mediated signaling, insulin secretion, and potentially the development of insulin resistance. Here, we summarize the recent progress on the role of CAV1 in diabetes and diabetic complications.

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“…When ER stress is prolonged or excessive, apoptotic cell death is executed by C/EBP homologous protein (CHOP) and other components of the apoptotic machinery [7]. There is accumulating evidence that some of these ER stress markers including XBP-1, BiP, and CHOP were elevated not only in chronic palmitate (PA) treated β-cell lines but also in pancreatic islets of patients with T2DM [8–11].…”

Section: Introductionmentioning

confidence: 99%

Perilipin5 protects against lipotoxicity and alleviates endoplasmic reticulum stress in pancreatic β-cells

Zhu

Zhang

et al. 2019

Nutr Metab (Lond)

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Background Chronic exposure of pancreatic β-cells to excess free fatty acids is thought to contribute to type 2 diabetes pathogenesis in obesity by impairing β-cell function and even leading to apoptosis. In β-cells, lipid droplet-associated protein perilipin 5 (PLIN5) has been shown to enhance insulin secretion by regulating intracellular lipid metabolism; the roles of PLIN5 in response to lipotoxicity remain poorly understood. Methods INS-1 β-cells were transfected with PLIN5-overexpression adenovirus (Ad-PLIN5) and treated with palmitate. C57BL/6 J male mice were fed with high fat diet and tail intravenous injected with adeno-associated virus overexpressing PLIN5 (AAV-PLIN5) in β-cells. Results Our data showed that palmitate and PPAR agonists including WY14643 (PPARα), GW501516 (PPARβ/δ), rosiglitazone (PPARγ) in vitro all induced PLIN5 expression in INS-1 cells. Under palmitate overload, although upregulating PLIN5 promoted lipid droplet storage, it alleviated lipotoxicity in INS-1 β-cells with improved cell viability, cell apoptosis and β-cell function. The protection role of PLIN5 in β-cell function observed in cell experiments were further verified in in vivo study indicated by mitigated glucose intolerance in high fat diet fed mice with β-cell-specific overexpression of PLIN5. Mechanistic experiments revealed that enhanced FAO induced by elevation of PLIN5, followed by decreased ER stress may be a major mechanism responsible for alleviation of lipotoxicity observed in the present study. Conclusions Our finding substantiated the important role of PLIN5 in protection against lipotoxicity in β-cells. Electronic supplementary material The online version of this article (10.1186/s12986-019-0375-2) contains supplementary material, which is available to authorized users.

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Caveolin-1 deficiency protects pancreatic β cells against palmitate-induced dysfunction and apoptosis

Cited by 21 publications

References 55 publications

Retracted : Salidroside from Rhodiola wallichiana var. cholaensis reverses insulin resistance and stimulates the GLP‐1 secretion by alleviating ROS‐mediated activation of MAPKs signaling pathway and mitigating apoptosis

Retracted : Salidroside from Rhodiola wallichiana var. cholaensis reverses insulin resistance and stimulates the GLP‐1 secretion by alleviating ROS‐mediated activation of MAPKs signaling pathway and mitigating apoptosis

Role of Caveolin-1 in Diabetes and Its Complications

Perilipin5 protects against lipotoxicity and alleviates endoplasmic reticulum stress in pancreatic β-cells

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