Introduction

Melatonin is a hormone known as having very strong anti-oxidant property. Senescence is a biological state characterized by the loss of cell replication and the changes consisting of a pro-inflammatory phenotype, leading to Senescence Associated Secretory Phenotype (SASP) which is now regarded as one of the fundamental processes of many degenerative diseases. Increased cell division count induces cell senescence via DNA damage in response to elevated Reactive Oxygen Species (ROS). We wanted to test whether melatonin could reduce apoptosis and stress induced premature pancreatic β-cell senescence induced by glucotoxicity and glucolipotoxicity.

Materials and method

Cultured rodent pancreatic β-cell line (INS-1 cell) was used. Glucotoxicity (HG: hyperglycemia) and glucolipotoxicity (HGP: hyperglycemia with palmitate) were induced by hyperglycemia and the addition of palmitate. The degrees of the senescence were measured by SA-β-Gal and P16^lnk4A staining along with the changes of cell viabilities, cell cycle-related protein and gene expressions, endogenous anti-oxidant defense enzymes, and Glucose Stimulated Insulin Secretion (GSIS), before and after melatonin treatment.

Results

Cultured INS-1 cells in HG and HGP conditions revealed accelerated senescence, increased apoptosis, cell cycle arrest, compromised endogenous anti-oxidant defense, and impaired glucose-stimulated insulin secretion. Melatonin decreased apoptosis and expressions of proteins related to senescence, increase the endogenous anti-oxidant defense, and improved glucose-stimulated insulin secretion.

Conclusion

Melatonin protected pancreatic β-cell from apoptosis, decreased expressions of the markers related to the accelerated senescence, and improved the biological deteriorations induced by glucotoxicity and glucolipotoxicity.

中文翻译：

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Melatonin 保护 INS-1 胰腺 β 细胞免受由糖毒性和糖脂毒性诱导的细胞凋亡和衰老。

介绍

褪黑激素是一种被称为具有很强抗氧化性能的激素。衰老是一种生物学状态，其特征在于细胞复制的丧失和由促炎表型组成的变化，导致衰老相关分泌表型 (SASP)，现在被认为是许多退行性疾病的基本过程之一。增加的细胞分裂计数通过响应升高的活性氧 (ROS) 的 DNA 损伤诱导细胞衰老。我们想测试褪黑激素是否可以减少由葡萄糖毒性和糖脂毒性诱导的细胞凋亡和应激诱导的胰腺 β 细胞过早衰老。

材料与方法

使用培养的啮齿动物胰腺 β 细胞系（INS-1 细胞）。葡萄糖毒性（HG：高血糖症）和糖脂毒性（HGP：棕榈酸酯的高血糖症）是由高血糖症和棕榈酸酯的添加引起的。通过SA-β-Gal和P16 ^lnk4A染色以及细胞活力、细胞周期相关蛋白和基因表达、内源性抗氧化防御酶和葡萄糖刺激胰岛素分泌（GSIS）的变化测量衰老程度，褪黑激素治疗前后。

结果

在 HG 和 HGP 条件下培养的 INS-1 细胞显示衰老加速、细胞凋亡增加、细胞周期停滞、内源性抗氧化防御受损和葡萄糖刺激的胰岛素分泌受损。褪黑激素减少细胞凋亡和衰老相关蛋白质的表达，增加内源性抗氧化防御，并改善葡萄糖刺激的胰岛素分泌。

结论

褪黑激素保护胰腺β细胞免于凋亡，降低与加速衰老相关的标志物的表达，并改善由糖毒性和糖脂毒性引起的生物学恶化。