{"title":"Influence of metformin on the expression of SESTRIN2, Nrf2, and TUG1 genes in the liver tissue of diabetic rats","authors":"Roya Zanganeh , Hamed Fanaei , Anis saadatmand , Ali dashtkar , Mohsen Saravani","doi":"10.1016/j.humgen.2025.201434","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>This study, focusing on the role of metformin in reducing oxidative stress, examined the effects of this drug on the expression of stress-related genes SESTRIN2, Nrf2, and TUG1 in the liver of diabetic rats.</div></div><div><h3>Methods</h3><div>Animals (<em>n</em> = 30) were divided into four groups: a control group (C), a control group treated with metformin (400 mg/kg/day) (C + M), a diabetic group (D), and a diabetic group treated with metformin (D + M) (400 mg/kg/day). Streptozotocin (STZ) was injected to induce diabetes. Serum levels of fasting blood glucose (FBG), triglycerides (TG), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL<img>C), total cholesterol (TC), and insulin were measured. Gene expression was assessed using the RT-PCR technique.</div></div><div><h3>Results</h3><div>The expression levels of Nrf2 and SESTRIN2 were decreased in group D compared to groups C and C + M but were not statistically significant (<em>p</em> > 0.05). However, the expression of Nrf2 and SESTRIN2 was increased in group D + M compared to group D, but only for Nrf2 was it significant (<em>p</em> = 0.0164). In addition, the expression of Nrf2 was significantly increased in group D + M compared to group C (<em>p</em> = 0.0299). The expression of TUG1 was increased in group D compared to group C, while the D + M group (1.36 ± 0.43) showed a decrease in TUG1 expression compared to group D (3 ± 1.64), which was not statistically significant. In addition, MET reduced the insulin resistance index, FBG, and lipid profile in the D + M group compared to the D group.</div></div><div><h3>Discussion</h3><div>Metformin suppresses oxidative stress by activating antioxidant pathways through increasing NRF2 gene expression, thereby improving diabetes and playing a protective role in the liver.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"45 ","pages":"Article 201434"},"PeriodicalIF":0.7000,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Human Gene","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2773044125000609","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
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Abstract
Background
This study, focusing on the role of metformin in reducing oxidative stress, examined the effects of this drug on the expression of stress-related genes SESTRIN2, Nrf2, and TUG1 in the liver of diabetic rats.
Methods
Animals (n = 30) were divided into four groups: a control group (C), a control group treated with metformin (400 mg/kg/day) (C + M), a diabetic group (D), and a diabetic group treated with metformin (D + M) (400 mg/kg/day). Streptozotocin (STZ) was injected to induce diabetes. Serum levels of fasting blood glucose (FBG), triglycerides (TG), LDL-cholesterol (LDL-C), HDL-cholesterol (HDLC), total cholesterol (TC), and insulin were measured. Gene expression was assessed using the RT-PCR technique.
Results
The expression levels of Nrf2 and SESTRIN2 were decreased in group D compared to groups C and C + M but were not statistically significant (p > 0.05). However, the expression of Nrf2 and SESTRIN2 was increased in group D + M compared to group D, but only for Nrf2 was it significant (p = 0.0164). In addition, the expression of Nrf2 was significantly increased in group D + M compared to group C (p = 0.0299). The expression of TUG1 was increased in group D compared to group C, while the D + M group (1.36 ± 0.43) showed a decrease in TUG1 expression compared to group D (3 ± 1.64), which was not statistically significant. In addition, MET reduced the insulin resistance index, FBG, and lipid profile in the D + M group compared to the D group.
Discussion
Metformin suppresses oxidative stress by activating antioxidant pathways through increasing NRF2 gene expression, thereby improving diabetes and playing a protective role in the liver.