Abstract：
BACKGROUND: It has been suggested that the anti-hyperglycemic effect of metformin could be associated with its impact on long non-coding RNA (lncRNA) expression levels. Accordingly, in the current study, we evaluated the effect of metformin on the expression of H19, MEG3, MALAT1, and GAS5 in in vitro and in vivo situations.
METHODS: The effect of hyperglycemia and metformin treatment on the lncRNAs expression level was evaluated in HepG2 cells. A total of 179 age- and sex-matched subjects, including 88 newly diagnosed patients with type 2 diabetes (T2D) and 91 healthy volunteers, were included in the case-control phase of the study. Moreover, 40 newly diagnosed patients participated in the study\'s open-labeled non-controlled clinical trial phase. The expression levels of lncRNA in HepG2 cells and whole blood samples were determined using QRT-PCR.
RESULTS: In vitro results showed that hyperglycemia induced H19 and MALAT1 and decreased GAS5 expression levels. Moreover, metformin decreased H19 and increased GAS5 expression in high glucose-treated cells. Case-control study findings revealed that the circulating levels of H19, MALAT1, and MEG3 were significantly elevated in T2D patients compared to the control subjects. Finally, results showed that the level of circulating H19 levels decreased while GAS5 increased in T2D patients after taking metformin for 2 months.
CONCLUSIONS: The results of the current study provided evidence that metformin could exert its effect in the treatment of T2D by altering the expression levels of H19 and GAS5.
METHODS: The effect of hyperglycemia and metformin treatment on the lncRNAs expression level was evaluated in HepG2 cells. A total of 179 age- and sex-matched subjects, including 88 newly diagnosed patients with type 2 diabetes (T2D) and 91 healthy volunteers, were included in the case-control phase of the study. Moreover, 40 newly diagnosed patients participated in the study\'s open-labeled non-controlled clinical trial phase. The expression levels of lncRNA in HepG2 cells and whole blood samples were determined using QRT-PCR.
RESULTS: In vitro results showed that hyperglycemia induced H19 and MALAT1 and decreased GAS5 expression levels. Moreover, metformin decreased H19 and increased GAS5 expression in high glucose-treated cells. Case-control study findings revealed that the circulating levels of H19, MALAT1, and MEG3 were significantly elevated in T2D patients compared to the control subjects. Finally, results showed that the level of circulating H19 levels decreased while GAS5 increased in T2D patients after taking metformin for 2 months.
CONCLUSIONS: The results of the current study provided evidence that metformin could exert its effect in the treatment of T2D by altering the expression levels of H19 and GAS5.
摘要：
背景：有人提出二甲双胍的抗高血糖作用可能与其对长非编码RNA（lncRNA）表达水平的影响有关。因此，在目前的研究中，我们在体外和体内情况下评估了二甲双胍对H19，MEG3，MALAT1和GAS5表达的影响。
方法：在HepG2细胞中评估高血糖和二甲双胍治疗对lncRNAs表达水平的影响。共有179名年龄和性别相匹配的受试者，包括88名新诊断的2型糖尿病（T2D）患者和91名健康志愿者，被纳入研究的病例对照阶段。此外，40名新诊断患者参加了本研究的开放标记非对照临床试验阶段。使用QRT-PCR测定HepG2细胞和全血样品中lncRNA的表达水平。
结果：体外结果显示高血糖诱导H19和MALAT1并降低GAS5表达水平。此外，二甲双胍在高糖处理的细胞中降低H19并增加GAS5表达。病例对照研究发现，与对照组相比，T2D患者的H19，MALAT1和MEG3的循环水平显着升高。最后,结果显示，服用二甲双胍2个月后，T2D患者的循环H19水平降低，而GAS5升高。
结论：本研究的结果提供了证据，证明二甲双胍可以通过改变H19和GAS5的表达水平在T2D的治疗中发挥作用。
方法：在HepG2细胞中评估高血糖和二甲双胍治疗对lncRNAs表达水平的影响。共有179名年龄和性别相匹配的受试者，包括88名新诊断的2型糖尿病（T2D）患者和91名健康志愿者，被纳入研究的病例对照阶段。此外，40名新诊断患者参加了本研究的开放标记非对照临床试验阶段。使用QRT-PCR测定HepG2细胞和全血样品中lncRNA的表达水平。
结果：体外结果显示高血糖诱导H19和MALAT1并降低GAS5表达水平。此外，二甲双胍在高糖处理的细胞中降低H19并增加GAS5表达。病例对照研究发现，与对照组相比，T2D患者的H19，MALAT1和MEG3的循环水平显着升高。最后,结果显示，服用二甲双胍2个月后，T2D患者的循环H19水平降低，而GAS5升高。
结论：本研究的结果提供了证据，证明二甲双胍可以通过改变H19和GAS5的表达水平在T2D的治疗中发挥作用。
