Bai Fuyan, Zheng Liping, Tao Li, Wang Shikai, Li Yuchen, Hou Lijun
The Second Affiliated Hospital of Shandong First Medical University, Tai'an, Shandong, China.
The First People's Hospital of Ningyang, Ningyang, China.
BMJ Open Diabetes Res Care. 2025 Jan 21;13(1):e004509. doi: 10.1136/bmjdrc-2024-004509.
Type 2 diabetes (T2D) is a chronic condition characterized by high levels of blood glucose resulting from the inefficiency of insulin. This study aims to explore the mechanism of TGFB-induced factor homeobox 1 (TGIF1) in the glycolipid metabolism of mice with T2D.
Mice with T2D were induced by high-fat diet and low-dose streptozotocin (STZ) injection. After TGIF1 was overexpressed in mice with T2D, the weight was monitored. The levels of fasting plasma glucose, fasting serum insulin, triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were measured. Staining assays were performed to observe liver tissue pathology and lipid accumulation. Liver function and oxidative stress were measured. Palmitic acid (PA)-induced primary hepatocytes were used to establish cell models. After TGIF1 was overexpressed in the cells, cell viability, cellular glucose uptake and consumption, and intracellular glycogen content were detected. The expression of TGIF1, miR-106b-5p, and early growth response 2 (EGR2) was detected and their binding relationships were analyzed. Combined experiments were conducted to validate the mechanism.
TGIF1 was downregulated in mice with T2D. TGIF1 overexpression reduced hyperglycemia and hyperlipidemia, improved insulin resistance, increased liver glycogen content, and attenuated lipid accumulation and glycolipid metabolism disorders in mice with T2D. TGIF1 was enriched on the miR-106b-5p promoter and promoted miR-106b-5p expression. miR-106b-5p inhibited EGR2 expression. miR-106b-5p inhibition or EGR2 overexpression partially reversed the alleviative effect of TGIF1 overexpression on glycolipid metabolism disorders.
TGIF1 reduces glycolipid metabolism disorders in mice with T2D through the miR-106b-5p/EGR2 axis.
2型糖尿病（T2D）是一种慢性疾病，其特征是由于胰岛素效率低下导致血糖水平升高。本研究旨在探讨转化生长因子β诱导因子同源盒1（TGIF1）在T2D小鼠糖脂代谢中的作用机制。
通过高脂饮食和低剂量链脲佐菌素（STZ）注射诱导T2D小鼠。在T2D小鼠中过表达TGIF1后，监测体重。测量空腹血糖、空腹血清胰岛素、甘油三酯、总胆固醇、低密度脂蛋白胆固醇和高密度脂蛋白胆固醇水平。进行染色分析以观察肝组织病理学和脂质积累。检测肝功能和氧化应激。使用棕榈酸（PA）诱导的原代肝细胞建立细胞模型。在细胞中过表达TGIF1后，检测细胞活力、细胞葡萄糖摄取和消耗以及细胞内糖原含量。检测TGIF1、miR-106b-5p和早期生长反应2（EGR2）的表达并分析它们的结合关系。进行联合实验以验证该机制。
T2D小鼠中TGIF1表达下调。TGIF1过表达降低了高血糖和高血脂，改善了胰岛素抵抗，增加了肝糖原含量，并减轻了T2D小鼠的脂质积累和糖脂代谢紊乱。TGIF1在miR-106b-5p启动子上富集并促进miR-106b-5p表达。miR-106b-5p抑制EGR2表达。抑制miR-106b-5p或过表达EGR2部分逆转了TGIF1过表达对糖脂代谢紊乱的缓解作用。
TGIF1通过miR-106b-5p/EGR2轴减轻T2D小鼠的糖脂代谢紊乱。
