Influence of metformin on the expression of SESTRIN2, Nrf2, and TUG1 genes in the liver tissue of diabetic rats

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.