To investigate the effect and underlying mechanism of Sijunzi Decoction in ameliorating insulin resistance (IR) within the pancreatic islets of rats with type 2 diabetes mellitus (T2DM).

A total of 40 Sprague-Dawley (SD) rats were randomly divided into control group (n=10, fed with normal diet) and high-sugar and high-fat group [n=30, fed with high-sugar and high-fat diet coupled with intraperitoneal injection of streptozotocin (STZ) to create a type 2 diabetes mellitus (T2DM) model]. The smoothly modeled SD rats were further randomly assigned into model group, positive control group (0.003 g·mL^-1) and experimental group (0.848 g·mL^-1). The normal group and model group were given distilled water by gavage, while the other two groups were administered the corresponding drugs by gavage for 4 consecutive weeks. Fasting blood glucose (FBG) was measured using a blood glucose meter. Serum levels of fasting insulin (FINS), total cholesterol (TC), total triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) in rats of each group were detected with commercial assay kits. The pancreatic index (PI) was calculated based on the detection of pancreatic tissue. Reverse transcription-polymerase chain reaction (RT-PCR) was employed to determine the mRNA expression levels of related proteins, and Western blotting was performed to ascertain the formulation standards of correlated total proteins.

The FBG, FINS, TC, TG, HDL-C, LDL-C and PI in the model group and experimental group were (13.60±0.61) mmol·L^-1 vs. (9.73±0.43) mmol·L^-1, (15.24±0.76) mIU·L^-1 vs. (12.39±1.13) mIU·L^-1, (5.42±0.41) mmol·L^-1 vs. (3.76±0.26) mmol·L^-1, (1.49±0.26) mmol·L^-1 vs. (0.65±0.05) mmol·L^-1, (0.82±0.06) mmol·L^-1 vs. (1.12±0.08) mmol·L^-1, (4.82±0.43) mmol·L^-1 vs. (3.02±0.42) mmol·L^-1, and (0.27±0.09)% vs. (0.34±0.02)%, respectively. The mRNA expression levels of INSR, IRS-1, PI3K, AKT, GLUT4, GSK-3β, and FOXO1 were 0.44±0.16 vs. 0.61±0.16, 0.48±0.13 vs. 0.72±0.16, 0.62±0.30 vs. 0.84±0.12, 0.74±0.20 vs. 0.92±0.02, 0.48±0.22 vs. 0.78±0.24, 1.90±0.16 vs. 1.56±0.25, and 1.83±0.16 vs. 1.60±0.21, respectively. The total protein expression levels of INSR, IRS-1, PI3K, AKT, GLUT4, GSK-3β, and FOXO1 were 0.59±0.29 vs. 0.82±0.18, 0.65±0.28 vs. 0.72±0.16, 0.49±0.14 vs. 0.74±0.15, 0.50±0.17 vs. 0.68±0.12, 0.65±0.28 vs. 0.86±0.14, 2.73±0.19 vs. 2.50±0.22, and 1.61±0.49 vs. 1.21±0.35, respectively. Compared with the model group, all the above indicators in the experimental group showed statistically significant differences (P<0.001, P<0.01, P<0.05).

Sijunzi Decoction can improve pancreatic insulin resistance (IR) in rats with type 2 diabetes mellitus (T2DM) by regulating the expression of 7 signaling factors in the upstream, middle and downstream of the PI3K/AKT signaling pathway.