BACKGROUND Our previous study revealed that microRNA-125a-5p plays a crucial role in regulating hepatic glycolipid metabolism by targeting STAT3 in type 2 diabetes mellitus (T2DM). Dioscin, a major active ingredient in Dioscoreae nipponicae rhizomes, displays various pharmacological activities, but its role in T2DM has not been reported. PURPOSE The aim of this study was to investigate the effect of dioscin on T2DM and elucidate its potential mechanism. METHODS The effect of dioscin on glycolipid metabolic disorder in insulin-induced HepG2 cells, palmitic acid-induced AML12 cells, high-fat diet- and streptozotocin- induced T2DM rats, and spontaneous T2DM KK-Ay mice were evaluated. Then, the possible mechanisms of dioscin were comprehensively evaluated. RESULTS Dioscin markedly alleviated the dysregulation of glycolipid metabolism in T2DM by reducing hyperglycemia and hyperlipidemia, improving insulin resistance, increasing hepatic glycogen content, and attenuating lipid accumulation. When the mechanism was investigated, dioscin was found to markedly elevate miR-125a-5p level and decrease STAT3 expression. Consequently, dioscin increased phosphorylation levels of STAT3, PI3K, AKT, GSK-3β, and FoxO1 and decreased gene levels of PEPCK, G6Pase, SREBP-1c, FAS, ACC, and SCD1, leading to an increase in glycogen synthesis and a decrease in gluconeogenesis and lipogenesis. The effects of dioscin on regulating miR-125a-5p/STAT3 pathway were verified by miR-125a-5p overexpression and STAT3 overexpression. CONCLUSIONS Dioscin showed potent anti-T2DM activity by improving the inhibitory effect of miR-125a-5p on STAT3 signaling to alleviate glycolipid metabolic disorder of T2DM.

中文翻译：

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薯di皂甙对2型糖尿病患者代谢糖脂代谢紊乱的影响及其可能机制。

背景技术我们先前的研究表明，microRNA-125a-5p通过靶向2型糖尿病（T2DM）中的STAT3，在调节肝糖脂代谢中起关键作用。薯os是薯Di中的主要活性成分，具有多种药理活性，但尚未报道其在T2DM中的作用。目的本研究的目的是研究薯os皂素对T2DM的作用并阐明其潜在机制。方法评估薯di中薯os皂甙元对胰岛素诱导的HepG2细胞，棕榈酸诱导的AML12细胞，高脂饮食和链脲佐菌素诱导的T2DM大鼠以及自发性T2DM KK-Ay小鼠糖脂代谢异常的影响。然后，综合评估薯os皂甙的可能机制。结果薯os皂素通过降低高血糖和高脂血症，改善胰岛素抵抗，增加肝糖原含量和减少脂质蓄积，从而显着减轻了T2DM中糖脂代谢的失调。在研究机理时，发现薯di皂甙能显着提高miR-125a-5p水平并降低STAT3表达。因此，薯os皂素增加STAT3，PI3K，AKT，GSK-3β和FoxO1的磷酸化水平，并降低PEPCK，G6Pase，SREBP-1c，FAS，ACC和SCD1的基因水平，从而导致糖原合成增加和糖原合成减少糖异生和脂肪形成。miR-125a-5p的过度表达和STAT3的过量表达证明了薯os皂甙对miR-125a-5p / STAT3通路的调节作用。