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Izadi A, Zarourati A, Boozarpour S, Ghalandar M, Lashkarboloki M, Momeni Moghaddam M et al . Metformin Increased Histone Deacetylases 1, 3, and 8 Expressions as Epigenetic Regulators in Type 2 Diabetic Patients. rbmb.net 2025; 14 (1) :85-94
URL: http://rbmb.net/article-1-1692-en.html
URL: http://rbmb.net/article-1-1692-en.html
Amin Izadi 
, Azam Zarourati , Sohrab Boozarpour * , Mohsen Ghalandar , Mina Lashkarboloki , Madjid Momeni Moghaddam , Masoud Fahimi
, Azam Zarourati , Sohrab Boozarpour * , Mohsen Ghalandar , Mina Lashkarboloki , Madjid Momeni Moghaddam , Masoud Fahimi
Department of Biology, Faculty of Basic Sciences, Gonbad Kavous University, Gonbad Kavous, Golestan, Iran.
Abstract: (688 Views)
Background: Type 2 diabetes is a complex disease resulting from interactions between genetic, epigenetic, and environmental factors. Histone deacetylases (HDAC) are essential epigenetic-regulatory enzymes that affect gene expression and, through metabolic homeostasis and beta-cell function regulation, play significant roles in the development and treatment of diabetes. In this study, we specifically focused on the effect of metformin, the first-line therapy for type 2 diabetes on the expression of class I HDAC genes.
Methods: A total of 60 patients were equally allocated into two groups: those receiving metformin treatment and those without treatment. Also, 60 subjects with normal glucose tolerance were divided into two groups: non-obese (n=30) and obese individuals (n=30). All biochemical and clinical factors were estimated using standard methods, and RT-qPCR was used to quantify the expression levels of the candidate genes in peripheral blood mononuclear cells of different groups.
Results: The metformin treatment group exhibited increased expression of HDAC1, HDAC3, and HDAC8 in comparison to the non-treatment group. Furthermore, the expression levels of HDAC 1, 2, and 3 were higher in the obese group than the non-obese. Interestingly, evaluation of biochemical and clinical factors revealed significant association between the expression of class I HDAC genes and several diabetes-related risk factors.
Conclusions: The current findings suggest that HDAC1, 3, and 8 genes expression are affected by metformin, and obesity has a substantial ability to increase the risk of diabetes. However, changes in HDAC expression may represent potential biomarkers and therapeutic targets for future clinical studies in diabetes, particularly in exploring combination therapies involving histone deacetylase inhibitors and metformin.
Methods: A total of 60 patients were equally allocated into two groups: those receiving metformin treatment and those without treatment. Also, 60 subjects with normal glucose tolerance were divided into two groups: non-obese (n=30) and obese individuals (n=30). All biochemical and clinical factors were estimated using standard methods, and RT-qPCR was used to quantify the expression levels of the candidate genes in peripheral blood mononuclear cells of different groups.
Results: The metformin treatment group exhibited increased expression of HDAC1, HDAC3, and HDAC8 in comparison to the non-treatment group. Furthermore, the expression levels of HDAC 1, 2, and 3 were higher in the obese group than the non-obese. Interestingly, evaluation of biochemical and clinical factors revealed significant association between the expression of class I HDAC genes and several diabetes-related risk factors.
Conclusions: The current findings suggest that HDAC1, 3, and 8 genes expression are affected by metformin, and obesity has a substantial ability to increase the risk of diabetes. However, changes in HDAC expression may represent potential biomarkers and therapeutic targets for future clinical studies in diabetes, particularly in exploring combination therapies involving histone deacetylase inhibitors and metformin.
Keywords: Body Mass Index, Diabetes Mellitus Type 2, Gene Expression, Histone Deacetylases, Metformin.
Type of Article: Original Article |
Subject:
Molecular Biology
Received: 2025/06/4 | Accepted: 2025/10/14 | Published: 2025/12/9
Received: 2025/06/4 | Accepted: 2025/10/14 | Published: 2025/12/9
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