Effect of serotonin 7 receptors and transcript variants on RIN-5F pancreatic beta cell line

IF 2.6 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro Pub Date : 2025-03-12 DOI:10.1016/j.tiv.2025.106050

Muhammed Yayla , Erdem Toktay , Bengul Ozdemir Sarikaya , Ugur Ermis , Sakir Akgun , Irfan Cinar

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引用次数: 0

Abstract

Purpose

The physiological effects of 5-HT7 receptors expressed in pancreatic beta cells have not yet been elucidated. We first aimed to investigate the effect of 5-HT7 receptor agonist (AS19) and antagonist (SB269970) application on insulin secretion in RIN-5F pancreatic beta cells. Subsequently, we aimed to investigate the effects of agonist and antagonist applications on cell damage induced by STZ.

Materials/Methods

Cell damage was caused by giving 5 mM STZ solution to the cells for 12 h. The protective effects of 5-HT7 receptor agonist and antagonist on this subsequent damage were investigated. IGF-1, TNF-α, TGF-B1, NF-KB, Bax, Caspase 3, Caspase 9, 5-HT7, 5HT7x2, 5HT7x3 mRNA expression levels were compared between groups.

Results

While agonist application stimulates insulin secretion, the effect of the antagonist varies.SB269970 reduced oxidative stress and downregulated TNF-a, TGF-B1 and NF-KB expression and also prevented apoptosis by decreasing Bax, caspase 3 and 9 levels against STZ-induced beta cell damage.

Conclusions

The effect of 5-HT7 receptors on insulin secretion and their effects against STZ damage will be guiding for more detailed studies in the treatment of diabetes and related diseases in the future.

Abstract Image

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血清素 7 受体和转录本变体对 RIN-5F 胰腺 beta 细胞系的影响

目的5-HT7受体在胰腺β细胞中表达的生理作用尚不清楚。我们首先旨在研究5-HT7受体激动剂（AS19）和拮抗剂（SB269970）应用对RIN-5F胰腺β细胞胰岛素分泌的影响。随后，我们旨在研究激动剂和拮抗剂应用对STZ诱导的细胞损伤的影响。材料/方法将5 mM STZ溶液作用于细胞12 h后，观察5- ht7受体激动剂和拮抗剂对细胞损伤的保护作用。比较各组间IGF-1、TNF-α、TGF-B1、NF-KB、Bax、Caspase 3、Caspase 9、5-HT7、5HT7x2、5HT7x3 mRNA表达水平。结果激动剂在刺激胰岛素分泌的同时，拮抗剂的作用各不相同。SB269970降低氧化应激，下调TNF-a、TGF-B1和NF-KB的表达，并通过降低Bax、caspase 3和9的水平来防止stz诱导的β细胞损伤。结论5-HT7受体对胰岛素分泌的影响及其对STZ损伤的作用将为今后更详细的研究糖尿病及相关疾病的治疗提供指导。

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来源期刊

Toxicology in Vitro 医学-毒理学

CiteScore

6.50

自引率

3.10%

发文量

181

审稿时长

65 days

期刊介绍： Toxicology in Vitro publishes original research papers and reviews on the application and use of in vitro systems for assessing or predicting the toxic effects of chemicals and elucidating their mechanisms of action. These in vitro techniques include utilizing cell or tissue cultures, isolated cells, tissue slices, subcellular fractions, transgenic cell cultures, and cells from transgenic organisms, as well as in silico modelling. The Journal will focus on investigations that involve the development and validation of new in vitro methods, e.g. for prediction of toxic effects based on traditional and in silico modelling; on the use of methods in high-throughput toxicology and pharmacology; elucidation of mechanisms of toxic action; the application of genomics, transcriptomics and proteomics in toxicology, as well as on comparative studies that characterise the relationship between in vitro and in vivo findings. The Journal strongly encourages the submission of manuscripts that focus on the development of in vitro methods, their practical applications and regulatory use (e.g. in the areas of food components cosmetics, pharmaceuticals, pesticides, and industrial chemicals). Toxicology in Vitro discourages papers that record reporting on toxicological effects from materials, such as plant extracts or herbal medicines, that have not been chemically characterized.