{"title":"二甲双胍介导的2型糖尿病表观遗传调节因子：DNMT1、TET1、OGG1和AID基因差异表达的研究","authors":"Sadaf Moeez, Syeda Kiran Riaz, Tanveer Ahmed Qaiser, Juneda Sarfraz, Asif Naseer, Shafiul Haque","doi":"10.1007/s00210-025-04700-z","DOIUrl":null,"url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is a widespread medical condition characterized by high blood glucose and inadequate insulin action, ultimately leading to insulin resistance. Genetic, epigenetic, and non-genetic factors are known to influence the pathogenesis of T2DM. Epigenetic alterations, principally DNA methylation and demethylation dynamics, play an important role, yet, their molecular mechanisms remain poorly understood. The present study aimed to study the expression patterns of DNMT1, TET1, OGG1, and AID genes involved in epigenetic regulation and insulin resistance in T2DM patients, along with in vitro validation using HepG2 insulin-resistant cell models. Blood samples were collected from 160 T2DM patients, categorized as metformin responders and non-responders, along with 40 healthy controls. Insulin resistance was induced in HepG2 cells, which were then treated with metformin and sulfonylureas at various concentrations and time intervals. qPCR was performed to study the differential expression of DNMT1, TET1, OGG1, and AID genes, using GAPDH as an internal control. Statistical analysis was done using SPSS software. Our results indicate that the expression of DNMT1, TET1, OGG1, and AID was significantly higher in T2DM metformin non-responders compared to T2DM metformin responders (P < 0.0001). Furthermore, we found that metformin treatment led to the down-expression of these genes in insulin-resistant HepG2 cells thus proving their in the regulation of the epigenetics state. This study highlights the contribution of epigenetic mechanisms in the pathogenesis of T2DM and underscores the therapeutic role of metformin in modulating key epigenetic regulators, precisely by altering DNA methylation/demethylation pathways through the regulation of key gene. These findings suggest that DNMT1, TET1, OGG1, and AID may serve as potential biomarkers and therapeutic targets for the management of T2DM.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Metformin-mediated modulation of epigenetic regulators in type 2 diabetes: A study on differential expression of DNMT1, TET1, OGG1, and AID genes.\",\"authors\":\"Sadaf Moeez, Syeda Kiran Riaz, Tanveer Ahmed Qaiser, Juneda Sarfraz, Asif Naseer, Shafiul Haque\",\"doi\":\"10.1007/s00210-025-04700-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Type 2 diabetes mellitus (T2DM) is a widespread medical condition characterized by high blood glucose and inadequate insulin action, ultimately leading to insulin resistance. Genetic, epigenetic, and non-genetic factors are known to influence the pathogenesis of T2DM. Epigenetic alterations, principally DNA methylation and demethylation dynamics, play an important role, yet, their molecular mechanisms remain poorly understood. The present study aimed to study the expression patterns of DNMT1, TET1, OGG1, and AID genes involved in epigenetic regulation and insulin resistance in T2DM patients, along with in vitro validation using HepG2 insulin-resistant cell models. Blood samples were collected from 160 T2DM patients, categorized as metformin responders and non-responders, along with 40 healthy controls. Insulin resistance was induced in HepG2 cells, which were then treated with metformin and sulfonylureas at various concentrations and time intervals. qPCR was performed to study the differential expression of DNMT1, TET1, OGG1, and AID genes, using GAPDH as an internal control. Statistical analysis was done using SPSS software. Our results indicate that the expression of DNMT1, TET1, OGG1, and AID was significantly higher in T2DM metformin non-responders compared to T2DM metformin responders (P < 0.0001). Furthermore, we found that metformin treatment led to the down-expression of these genes in insulin-resistant HepG2 cells thus proving their in the regulation of the epigenetics state. This study highlights the contribution of epigenetic mechanisms in the pathogenesis of T2DM and underscores the therapeutic role of metformin in modulating key epigenetic regulators, precisely by altering DNA methylation/demethylation pathways through the regulation of key gene. These findings suggest that DNMT1, TET1, OGG1, and AID may serve as potential biomarkers and therapeutic targets for the management of T2DM.</p>\",\"PeriodicalId\":18876,\"journal\":{\"name\":\"Naunyn-Schmiedeberg's archives of pharmacology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2025-10-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Naunyn-Schmiedeberg's archives of pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00210-025-04700-z\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Naunyn-Schmiedeberg's archives of pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00210-025-04700-z","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Metformin-mediated modulation of epigenetic regulators in type 2 diabetes: A study on differential expression of DNMT1, TET1, OGG1, and AID genes.
Type 2 diabetes mellitus (T2DM) is a widespread medical condition characterized by high blood glucose and inadequate insulin action, ultimately leading to insulin resistance. Genetic, epigenetic, and non-genetic factors are known to influence the pathogenesis of T2DM. Epigenetic alterations, principally DNA methylation and demethylation dynamics, play an important role, yet, their molecular mechanisms remain poorly understood. The present study aimed to study the expression patterns of DNMT1, TET1, OGG1, and AID genes involved in epigenetic regulation and insulin resistance in T2DM patients, along with in vitro validation using HepG2 insulin-resistant cell models. Blood samples were collected from 160 T2DM patients, categorized as metformin responders and non-responders, along with 40 healthy controls. Insulin resistance was induced in HepG2 cells, which were then treated with metformin and sulfonylureas at various concentrations and time intervals. qPCR was performed to study the differential expression of DNMT1, TET1, OGG1, and AID genes, using GAPDH as an internal control. Statistical analysis was done using SPSS software. Our results indicate that the expression of DNMT1, TET1, OGG1, and AID was significantly higher in T2DM metformin non-responders compared to T2DM metformin responders (P < 0.0001). Furthermore, we found that metformin treatment led to the down-expression of these genes in insulin-resistant HepG2 cells thus proving their in the regulation of the epigenetics state. This study highlights the contribution of epigenetic mechanisms in the pathogenesis of T2DM and underscores the therapeutic role of metformin in modulating key epigenetic regulators, precisely by altering DNA methylation/demethylation pathways through the regulation of key gene. These findings suggest that DNMT1, TET1, OGG1, and AID may serve as potential biomarkers and therapeutic targets for the management of T2DM.
期刊介绍：
Naunyn-Schmiedeberg''s Archives of Pharmacology was founded in 1873 by B. Naunyn, O. Schmiedeberg and E. Klebs as Archiv für experimentelle Pathologie und Pharmakologie, is the offical journal of the German Society of Experimental and Clinical Pharmacology and Toxicology (Deutsche Gesellschaft für experimentelle und klinische Pharmakologie und Toxikologie, DGPT) and the Sphingolipid Club. The journal publishes invited reviews, original articles, short communications and meeting reports and appears monthly. Naunyn-Schmiedeberg''s Archives of Pharmacology welcomes manuscripts for consideration of publication that report new and significant information on drug action and toxicity of chemical compounds. Thus, its scope covers all fields of experimental and clinical pharmacology as well as toxicology and includes studies in the fields of neuropharmacology and cardiovascular pharmacology as well as those describing drug actions at the cellular, biochemical and molecular levels. Moreover, submission of clinical trials with healthy volunteers or patients is encouraged. Short communications provide a means for rapid publication of significant findings of current interest that represent a conceptual advance in the field.
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