OBJECTIVE To investigate the ameliorative effect of Sijunzi decoction(SJZD) on adipose insulin resistance in type 2 diabetes mellitus(T2DM) rats and its underlying mechanism.

METHODS The model was established in SD rats using a high-sugar, high-fat diet combined with streptozotocin intervention. Animals were randomly divided into: normal control group, model control group, metformin group, and SJZD group. Intragastric administration was performed once daily for 4 weeks. Changes in reaction sensitivity, spontaneous activity frequency, food intake, water intake, and body weight were measured in each group. Oral glucose tolerance test(OGTT), insulin tolerance test(ITT), fasting blood glucose(FBG), and fasting insulin(FINS) were measured in each group. Followed by the calculation of insulin resistance(HOMA-IR) and β-cell function(HOMA-β) using the homeostasis model assessment method. Liver index, serum levels of total cholesterol(TC), total triglycerides(TG), high-density lipoprotein cholesterol(HDL-C), and low-density lipoprotein cholesterol(LDL-C) were measured. Pathological changes in adipose tissue were observed using HE staining. Total mRNA and total protein expression levels of INSR, IRS-1, PI3K, AKT, GLUT4, GSK-3β, and FOX-O1 in the adipose tissue were detected using RT-qPCR and Western blotting.

RESULTS SJZD significantly improved the response sensitivity and spontaneous activity frequency in T2DM rats(P<0.01), ameliorated symptoms of polydipsia and polyphagia, and significantly increased body weight(P<0.01). It significantly reduced OGTT, ITT, FBG, and HOMA-IR(P<0.01), significantly decreased FINS levels(P<0.05), and significantly increased HOMA-β(P<0.01). SJZD significantly reduced serum TC content(P<0.01), significantly decreased TG and LDL-C content(P<0.05), and significantly increased HDL-C content(P<0.05). Adipose histopathological observation showed that SJZD improved the morphology, size, and degeneration of adipocytes in T2DM rats and reduced pathological conditions such as lipid droplet vacuoles. RT-qPCR and Western blotting results demonstrated that SJZD up-regulated the total mRNA expression of INSR, IRS-1, PI3K, AKT, and GLUT4(P<0.01 or P<0.05), and down-regulated the total mRNA expression of GSK-3β and FOX-O1(P<0.01 or P<0.05). SJZD up-regulated the total protein expression of INSR, IRS-1, and GLUT4 while down-regulating GSK-3β and FOX-O1(P<0.01 or P<0.05). It also up-regulated PI3K and AKT total protein expression, but the difference was not statistically significant.

CONCLUSION SJZD can ameliorate insulin resistance in the adipose tissue of T2DM rats by regulating the expression of seven signaling factors of the PI3K/AKT signaling pathway.