Combined administration of Gegen Yinlian decoctio n and metformin ameliorates liver metabolic disorder in rats by regulating miR 195 5p/IRS1/PI3K/AKT axis

Abstract

Purpose: To investigate the effect of Gegen Yinlian decoction (GYD), made from lobed kudzuvine root, baicalensis, huanglian and liquorice, and metformin on liver metabolism dysfunction in type 2 diabetes mellitus (T2DM) rats. Methods: Wistar rats were treated with high-fat diet and a single intraperitoneal streptozotocin (STZ) injection to establish T2DM model. Thereafter, the T2DM-rats were treated with GYD and metformin (GYD/metformin). Serum triglyceride (TG), TC, LDL, and HDL levels, as well as glucose and insulin tolerance of the rats were evaluated. Furthermore, the effects of GYD/metformin treatment on the expressions of the related genes were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunoblot assay. Results: After GYD-metformin treatment, the metabolic indicators in T2DM rats significantly improved (p < 0.05). However, there was decrease in t liver miR-1955p expressions. Silencing miR-195-5p improved glucose consumption and triglyceride levels of palmitate (PA)-induced pathological state in ALM12 cells (p < 0.05). Furthermore, miR-195-5p targeted insulin receptor substrate 1 (IRS1). Suppression of IRS1 partly annulled the impact of miR-195-5p silencing on ALM12 cell model. Moreover, IRS1 downregulation significantly mitigated the impact of the silencing on PI3K/AKT pathway activity (p < 0.05). Conclusion: Combination of GYD with metformin ameliorated dysfunctional liver metabolism via control of miR-195-5p/IRS1/PI3K/AKT axis.