IGF1R as a protective target in antidiabetic drug-mediated prevention of erectile dysfunction: Insights from genetics

IF 2.8 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology Pub Date : 2025-07-12 DOI:10.1016/j.reprotox.2025.108999

Yuqi Li, Juan Wang, Tao Zhou, Zhiyu Liu, Chunyang Meng, Qingfu Deng

{"title":"IGF1R as a protective target in antidiabetic drug-mediated prevention of erectile dysfunction: Insights from genetics","authors":"Yuqi Li, Juan Wang, Tao Zhou, Zhiyu Liu, Chunyang Meng, Qingfu Deng","doi":"10.1016/j.reprotox.2025.108999","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>In recent years, antidiabetic drugs have been increasingly repurposed for conditions beyond diabetes. However, their effects on erectile dysfunction (ED) remain inadequately understood. This study utilizes Mendelian randomization (MR) analysis to investigate the potential impact of antidiabetic drug targets on the risk of ED.</div></div><div><h3>Method</h3><div>We retrieved target gene information for eight classes of antidiabetic drugs from the DrugBank and GeneCards databases and subsequently identified instrumental variables for the corresponding genes using data from the eQTLGen consortium. Following data integration, we conducted MR, meta-analysis, and summary-data-based mendelian randomization (SMR) to systematically investigate the potential causal relationship between antidiabetic drug target genes and ED. Furthermore, we performed sensitivity analyses to assess the robustness and reliability of the observed associations.</div></div><div><h3>Result</h3><div>This study investigated the potential association between 24 antidiabetic drug target genes and ED, identifying 11 positive target genes and included in subsequent analyses. Using MR, meta-analysis, and summary-data-based MR, we observed a significant negative correlation between IGF1R and ED (OR 0.907, 95 % CI 0.859–0.959, P < 0.001). These findings suggest that IGF1R may exert a protective effect against ED, offering novel theoretical support for the potential repurposing of antidiabetic drugs in ED treatment.</div></div><div><h3>Conclusion</h3><div>Our findings indicate that elevated expression of IGF1R may be associated with a reduced risk of erectile dysfunction (ED). This observation implies that the rational application of insulin and its analogs could confer potential preventive benefits against ED, offering novel theoretical insights for the development of targeted therapeutic strategies.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 108999"},"PeriodicalIF":2.8000,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Reproductive toxicology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0890623825001704","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"REPRODUCTIVE BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

In recent years, antidiabetic drugs have been increasingly repurposed for conditions beyond diabetes. However, their effects on erectile dysfunction (ED) remain inadequately understood. This study utilizes Mendelian randomization (MR) analysis to investigate the potential impact of antidiabetic drug targets on the risk of ED.

Method

We retrieved target gene information for eight classes of antidiabetic drugs from the DrugBank and GeneCards databases and subsequently identified instrumental variables for the corresponding genes using data from the eQTLGen consortium. Following data integration, we conducted MR, meta-analysis, and summary-data-based mendelian randomization (SMR) to systematically investigate the potential causal relationship between antidiabetic drug target genes and ED. Furthermore, we performed sensitivity analyses to assess the robustness and reliability of the observed associations.

Result

This study investigated the potential association between 24 antidiabetic drug target genes and ED, identifying 11 positive target genes and included in subsequent analyses. Using MR, meta-analysis, and summary-data-based MR, we observed a significant negative correlation between IGF1R and ED (OR 0.907, 95 % CI 0.859–0.959, P < 0.001). These findings suggest that IGF1R may exert a protective effect against ED, offering novel theoretical support for the potential repurposing of antidiabetic drugs in ED treatment.

Conclusion

Our findings indicate that elevated expression of IGF1R may be associated with a reduced risk of erectile dysfunction (ED). This observation implies that the rational application of insulin and its analogs could confer potential preventive benefits against ED, offering novel theoretical insights for the development of targeted therapeutic strategies.

查看原文本刊更多论文

IGF1R作为抗糖尿病药物介导的勃起功能障碍预防的保护靶点：遗传学的见解。

背景：近年来，降糖药越来越多地用于糖尿病以外的疾病。然而，它们对勃起功能障碍（ED）的影响仍不充分了解。方法：从DrugBank和GeneCards数据库中检索8类降糖药的靶基因信息，随后利用eQTLGen联盟的数据确定相应基因的工具变量。在数据整合之后，我们进行了核磁共振、荟萃分析和基于汇总数据的孟德尔随机化（SMR），以系统地研究降糖药物靶基因与ED之间的潜在因果关系。此外，我们进行了敏感性分析，以评估观察到的关联的稳健性和可靠性。结果：本研究探讨了24个降糖药物靶基因与ED的潜在关联，鉴定出11个阳性靶基因并纳入后续分析。通过磁共振、荟萃分析和基于汇总数据的磁共振，我们观察到IGF1R和ED之间存在显著的负相关（OR 0.907, 95% CI 0.859-0.959, P < 0.001）。这些发现提示IGF1R可能对ED发挥保护作用，为ED治疗中抗糖尿病药物的潜在再利用提供了新的理论支持。结论：我们的研究结果表明，IGF1R的表达升高可能与勃起功能障碍（ED）的风险降低有关。这一观察结果表明，胰岛素及其类似物的合理应用可能对ED具有潜在的预防作用，为开发靶向治疗策略提供了新的理论见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Reproductive toxicology 生物-毒理学

CiteScore

6.50

自引率

3.00%

发文量

131

审稿时长

45 days

期刊介绍： Drawing from a large number of disciplines, Reproductive Toxicology publishes timely, original research on the influence of chemical and physical agents on reproduction. Written by and for obstetricians, pediatricians, embryologists, teratologists, geneticists, toxicologists, andrologists, and others interested in detecting potential reproductive hazards, the journal is a forum for communication among researchers and practitioners. Articles focus on the application of in vitro, animal and clinical research to the practice of clinical medicine. All aspects of reproduction are within the scope of Reproductive Toxicology, including the formation and maturation of male and female gametes, sexual function, the events surrounding the fusion of gametes and the development of the fertilized ovum, nourishment and transport of the conceptus within the genital tract, implantation, embryogenesis, intrauterine growth, placentation and placental function, parturition, lactation and neonatal survival. Adverse reproductive effects in males will be considered as significant as adverse effects occurring in females. To provide a balanced presentation of approaches, equal emphasis will be given to clinical and animal or in vitro work. Typical end points that will be studied by contributors include infertility, sexual dysfunction, spontaneous abortion, malformations, abnormal histogenesis, stillbirth, intrauterine growth retardation, prematurity, behavioral abnormalities, and perinatal mortality.