Sulfated Fucogalactan From Laminaria Japonica Ameliorates β-Cell Failure by Attenuating Mitochondrial Dysfunction via SIRT1–PGC1-α Signaling Pathway Activation

Pancreatic β-cell dysfunction is a key factor in the development of type 2 diabetes. Pancreatic β-cell senescence accelerates abnormal glucose metabolism, which decreases insulin secretion and cell regeneration ability, eventually leading to diabetes. A cholesterol oxidation product, 7-ketocholesterol (7-KC) can affect pancreatic β-cell function. However, its role in pancreatic β-cell senescence has not been reported. We investigated the role of 7-KC in pancreatic β-cell senescence and its underlying molecular mechanism in MIN6 cells. MIN6 cells were treated with 25 μmol/L 7-KC for 24 h and the proportion of senescent cells was detected based on senescence-associated β-galactosidase (SA-β-gal) activity. The cell cycle, DNA damage, and the senescence-associate secretory phenotype (SASP) and protein expression were detected by flow cytometry, immunofluorescence, and western blotting, respectively. 7-KC can significantly increase SA-β-gal activity, promoted G0/G1 arrest, DNA damage, and interleukin-1β expression in MIN6 cells and significantly inhibited insulin synthesis. Further studies indicated that 7-KC induced β-cell senescence by inhibiting the SIRT1/CDK4–Rb – E2F1 signaling pathway.

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“…The results are in accordance with reports that IL-1β was increased in β-cells and was an independent predictor of diabetes. 21 , 43 , 44 …”

Section: Discussionmentioning

confidence: 99%

7-Ketocholesterol accelerates pancreatic β-cell senescence by inhibiting the SIRT1/CDK4–Rb–E2F1 signaling pathway

Zhu

Wang

et al. 2023

Islets

Self Cite

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“…Moreover, SIRT1 directly interacts with and deacetylates PGC-1α, forming a transcriptional complex to determine the expression of other metabolic genes [41,42]. PGC1-α is a transcriptional co-activator that regulates the activity of transcription factors known to play a crucial role in mitochondrial function [43].…”

Section: Discussionmentioning

confidence: 99%

Melatonin Modulates the SIRT1-Related Pathways via Transdermal Cryopass-Laser Administration in Prostate Tumor Xenograft

Bonomini,

Favero,

Petroni

et al. 2023

Cancers

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Melatonin displays antitumor activity in several types of malignancies; however, the best delivery route and the underlying mechanisms are still unclear. Alternative non-invasive delivery route based on transdermal administration of melatonin by cryopass-laser treatment demonstrated efficiency in reducing the progression of LNCaP prostate tumor cells xenografted into nude mice by impairing the biochemical pathways affecting redox balance. Here, we investigated the impact of transdermal melatonin on the tumor dimension, microenvironment structure, and SIRT1-modulated pathways. Two groups (vehicle cryopass-laser and melatonin cryopass-laser) were treated for 6 weeks (3 treatments per week), and the tumors collected were analyzed for hematoxylin eosin staining, sirius red, and SIRT1 modulated proteins such as PGC-1α, PPARγ, and NFkB. Melatonin in addition to simple laser treatment was able to boost the antitumor cancer activity impairing the tumor microenvironment, increasing the collagen structure around the tumor, and modulating the altered SIRT1 pathways. Transdermal application is effective, safe, and feasible in humans as well, and the significance of these findings necessitates further studies on the antitumor mechanisms exerted by melatonin.

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“…The circular RNA hsa_circ_0115355 prevented T2DM by enhancing pancreatic β -cell activity and controlling SIRT-1 expression by binding to microRNA, miR-145 [ 142 ]. The sulfated fucogalactan (SFG) protected β -cells from H 2 O 2 by likely attenuating mitochondrial dysfunction via the SIRT-1-PGC1 signalling pathway, establishing SFG as a mechanistic basis for SFG as a viable therapeutic target for pancreatic β -cell protection [ 143 ].…”

Section: Self-tolerance Safeguard: Hdacs Influence On Pancreatic ...mentioning

confidence: 99%

Exploring histone deacetylases in type 2 diabetes mellitus: pathophysiological insights and therapeutic avenues

Kumar,

Aburawi,

Ljubisavljevic

et al. 2024

Clin Epigenet

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Diabetes mellitus is a chronic disease that impairs metabolism, and its prevalence has reached an epidemic proportion globally. Most people affected are with type 2 diabetes mellitus (T2DM), which is caused by a decline in the numbers or functioning of pancreatic endocrine islet cells, specifically the β-cells that release insulin in sufficient quantity to overcome any insulin resistance of the metabolic tissues. Genetic and epigenetic factors have been implicated as the main contributors to the T2DM. Epigenetic modifiers, histone deacetylases (HDACs), are enzymes that remove acetyl groups from histones and play an important role in a variety of molecular processes, including pancreatic cell destiny, insulin release, insulin production, insulin signalling, and glucose metabolism. HDACs also govern other regulatory processes related to diabetes, such as oxidative stress, inflammation, apoptosis, and fibrosis, revealed by network and functional analysis. This review explains the current understanding of the function of HDACs in diabetic pathophysiology, the inhibitory role of various HDAC inhibitors (HDACi), and their functional importance as biomarkers and possible therapeutic targets for T2DM. While their role in T2DM is still emerging, a better understanding of the role of HDACi may be relevant in improving insulin sensitivity, protecting β-cells and reducing T2DM-associated complications, among others.

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Sulfated Fucogalactan From Laminaria Japonica Ameliorates β-Cell Failure by Attenuating Mitochondrial Dysfunction via SIRT1–PGC1-α Signaling Pathway Activation

Cited by 8 publications

References 51 publications

7-Ketocholesterol accelerates pancreatic β-cell senescence by inhibiting the SIRT1/CDK4–Rb–E2F1 signaling pathway

7-Ketocholesterol accelerates pancreatic β-cell senescence by inhibiting the SIRT1/CDK4–Rb–E2F1 signaling pathway

Melatonin Modulates the SIRT1-Related Pathways via Transdermal Cryopass-Laser Administration in Prostate Tumor Xenograft

Exploring histone deacetylases in type 2 diabetes mellitus: pathophysiological insights and therapeutic avenues

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