Purpose: Patients with type 1 diabetes (T1D) are associated with a high risk of multiple complications, so the development of T1D treatment is urgently needed. This study was set out to explore the molecular mechanism of metformin in the treatment of T1D insulin resistance.
Patients and Methods: Subcutaneous adipose tissues were collected from 68 T1D patients and 51 healthy controls. Insulin resistance model rats and cells were constructed and treated with metformin respectively. Western blot was used to detect p53 and RAP2A protein levels, and qPCR was utilized to measure p53 and RAP2A mRNA levels. SiRNA and RAP2A siRNA vectors were constructed to observe their effects on insulin resistance model cells.
Results: In T1D, p53 was up-regulated, while RAP2A was down-regulated. Metformin could effectively improve insulin resistance and inflammatory response while down-regulating p53 and up-regulating RAP2A. P53 induced insulin resistance and inflammatory response by inhibiting RAP2A and promoted apoptosis.
Conclusion: Metformin improves T1D insulin resistance and inflammatory response through p53/RAP2A pathway, and the regulation of p53/RAP2A pathway is conducive to improving the efficacy of metformin in the treatment of insulin resistance.

Keywords: type 1 diabetes, p53, RAP2A, insulin resistance, metformin


中文翻译：

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二甲双胍通过在体外和体内调节 p53 和 RAP2A 降低 1 型糖尿病的胰岛素抵抗。

目的： 1型糖尿病（T1D）患者发生多种并发症的风险很高，因此迫切需要开发T1D治疗。本研究旨在探讨二甲双胍治疗T1D胰岛素抵抗的分子机制。
患者和方法：收集了 68 名 T1D 患者和 51 名健康对照者的皮下脂肪组织。构建胰岛素抵抗模型大鼠和细胞，分别用二甲双胍处理。Western印迹用于检测p53和RAP2A蛋白水平，qPCR用于测量p53和RAP2A mRNA水平。构建siRNA和RAP2A siRNA载体以观察它们对胰岛素抵抗模型细胞的影响。
结果：在 T1D 中，p53 上调，而 RAP2A 下调。二甲双胍可有效改善胰岛素抵抗和炎症反应，同时下调p53和上调RAP2A。P53通过抑制RAP2A诱导胰岛素抵抗和炎症反应并促进细胞凋亡。
结论：二甲双胍通过p53/RAP2A通路改善T1D胰岛素抵抗和炎症反应，调控p53/RAP2A通路有利于提高二甲双胍治疗胰岛素抵抗的疗效。

关键词： 1型糖尿病，p53，RAP2A，胰岛素抵抗，二甲双胍