Yunpi Heluo decoction attenuates insulin resistance by regulating liver miR-29a-3p in Zucker diabetic fatty rats

• Published in: Journal of ethnopharmacology 2019-10, Vol.243, p.111966-111966, Article 111966
• Main Authors: Mao, Zhu-Jun, Weng, Si-Ying, Lin, Min, Chai, Ke-Fu
• Format: Article
• Language: English
• Subjects: Animals; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - pathology; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; Gene Expression Regulation - drug effects; Hep G2 Cells; Humans; Hypoglycemic Agents - pharmacology; Hypoglycemic Agents - therapeutic use; Insulin receptor signaling pathway; Insulin Receptor Substrate Proteins - genetics; Insulin Receptor Substrate Proteins - metabolism; Insulin resistance; Insulin Resistance - genetics; IRS1; Liver - drug effects; Liver - metabolism; Liver - pathology; Male; MicroRNAs - genetics; miRNA; Rats, Zucker; Yunpiheluo decoction
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2019.111966

Yunpiheluo (YPHL) decoction is a Chinese herbal formula with unique advantages for the treatment of type 2 diabetes mellitus (T2DM). The aim of the present study was to investigate changes in miRNA expression and downstream gene expression in Zucker diabetic fatty (ZDF) rats treated with YPHL to determine whether YPHL could be used as an adjuvant treatment of T2DM. Serum and liver total cholesterol (TC) and triglycerides (TG) levels, insulin resistance index (IR) and differentially expressed miRNAs were detected in a T2DM ZDF rat model. miRNA target prediction was based on bioinformatic algorithms and dual luciferase reporter assay. Protein expression of genes in the insulin receptor signaling pathway was detected by Western blot. The IR cell model was established and the effects of lyophilized YPHL powder on the protein expressions were observed by transfecting specific miRNA mimics and inhibitors. The miR-29a-3p expression level was significantly increased in the liver of ZDF rats. Insulin receptor substrate 1 (IRS1) was the target gene of miR-29a-3p. IRS1 mRNA and protein expressions of IRS1, IRS1 (phospho S307), protein kinase B (Akt), Akt (phosphor ser473) and pyruvate dehydrogenase lipoamide kinase isozyme 1 (PDK1) were decreased significantly. miR-29a-3p over-expression decrease IRS1 and the others protein expressions in the HepG2 IR cell model while anti-miR-29a-3p showed the opposite result. The miR-29a-3p level was decreased, and the expressions of IRS1 mRNA and the above proteins were all increased after YPHL treatment. miR-29a-3p played a functional role in insulin receptor signaling in the liver of ZDF rats. YPHL decoction attenuated IR in T2DM probably by down-regulating or maintaining the miR-29a-3p level, increasing the expression of IRS1 mRNA and its phosphorylated proteins, and regulating the expression of insulin receptor signaling-related proteins. YPHL may prove to be an alternative treatment for T2DM. [Display omitted]