Yiqi Huazhuo decoction attenuates insulin resistance by regulating liver lncRNA-PID1 in ZDF rats 

Abstract

Yiqi Huazhuo Decoction(YD), a traditional Chinese herbal formula, demonstrates notable therapeutic efficacy in the management of type2 diabetes mellitus(T2DM). This study aims to investigate the expression patterns of lncPID1, PID1, and downstream genes in T2DM rats subjected to YD treatment, elucidating the potential role of YD as an adjunctive therapy for T2DM. Two intervention groups, namely YD-lo(15 mg/kg/d) and YD-hi(30 mg/kg/d), were established. YD intervention resulted in decreased blood glucose, insulin resistance(IR), and lipid levels in rats. The relative expression of lncPID1, mRNA-PID1 and Foxo1 was reduced, while the expressions of IRS1 and p-Aktser473 were upregulated in the rat liver. Following YD treatment, expressions of lncPID1, PID1, and Foxo1 were downregulated in BRL-3A-IR cells, whereas IRS1 and Akt expressions were upregulated. Conversely, inhibiting lncPID1 demonstrated the opposite effect, indicating that YD modulates downstream target genes through lncPID-mediated regulation. The binding between lncPID1 and mRNA-PID1 was validated by RIP-PCR. It's posited that lncPID1 plays a pivotal role in the insulin receptor signaling pathway in the liver of ZDF rats. YD suppresses both lncPID1 and PID1, thereby enhancing the expression of IRS1 and Akt. This cascade effect further inhibits Foxo1 expression, promotes liver glycogen synthesis and mitigates insulin resistance in T2DM.