| Objective To observe the effects of Wu-zi Hypoglycemic Formula on blood glucoseand insulin resistance (IR), and explore its action mechanism of IR improvement inT2DM rats.Method The type2diabetes model of rat was established by high-fat diet and smalldose intraperitoneal injections of streptozotocin. Model rats were randomly divided into5groups: the model group administrated with purified water, the Metformin group withmetformin suspension, Wu-zi Hypoglycemic Formula groups of low dose, middle doseand high dose with water extracts of different doses respectively for6weeks. Meanwhile,normal group was set treated with purified water. The interventions were administratedby ig for6weeks. The general conditions were observed, and the oral glucose tolerancetests were performed and analyzed before and after the drug administration. At the end ofthe sixth week, aortic blood was collected for the measurement of serum SOD, MDA,hsCRP. Homa-IR (CP) formula was used to evaluate IR index involving fast bloodglucose and C peptid. Rectus femoris muscle at the left hind limb and liver were quicklysampled, cleaned with saline rinse, and put in liquid nitrogen for cryopreservation.Western Blot was used for protein contents of p-IRS-1(Tyr895), IRS-1, PTP1B, and GLUT4in skeletal muscle. The liver was taken for the measurement of glycogen content throughglycogen measuring kit and protein expressions of p-AKT(ser473), AKT, p-GSK-3β(ser9)and GSK-3β by Western Blot.Results1Compared with normal group, rats’ general condition in model group weredepression, polydipsia, polyphagia, urorrhagia, diarrhea, dry and lackluster hair,decreased activity, slow in response; Compared with model group, the rats’ conditionabove were improved significantly in groups of Wu-zi Hypoglycemic Formula.2Compared with that in normal group, the levels of fasting blood glucose and2hpostprandial blood glucose, insulin resistance index were increased in model group; Wu-zi Hypoglycemic Formula could significantly reduce the blood glucose levels and lowerinsulin resistance index in T2DM rats, with significant differences in all of the itemsabove (P<0.05).3Compared with normal group, the levels of the serum MDA andhsCRP were increased, while the SOD levels were decreased in the rats of the modelgroup (P<0.05); the serum MDA level was decreased, while the SOD increased in Wu-ziHypoglycemic Formula groups (P<0.05). In addition, serum hsCRP level was decreasedobviously in Wu-zi Hypoglycemic Formula group of middle-dose (P<0.05).4Comparedwith normal group, p-IRS-1(Tyr895)protein expression was significantly lowered, andphosphorylation level of IRS-1at tyrosine significantly lowered, and PTP1B proteinexpression increased significantly, and GLUT4protein expression decreased in the modelgroup (P<0.05). Compared with model group, p-IRS-1(Tyr895)protein expression wasincreased significantly, and phosphorylation level of IRS-1at tyrosine increasedsignificantly, and PTP1B protein expression significantly decreased, and GLUT4proteinexpression increased in Wu-zi Hypoglycemic Formula groups (P<0.05).5Compared with normal group, the liver glycogen content was decreased, and the expression and itsphosphorylation of AKT were decreased, and the expression of GSK-3β increased but itsphosphorylation decreased in rats of the model group (P<0.05); Compared with modelgroup, the liver glycogen content was increased, and the expression of AKT and itsphosphorylation were increased and the expression of GSK-3β decreased while itsphosphorylation increased in rats of Wu-zi Hypoglycemic Formula groups (P<0.05).Conclusions1Wu-zi Hypoglycemic Formula can reduce the levels of fast bloodglucose and2h postprandial blood glucose, and improve the condition in oral glucosetolerance test in T2DM model rats.2Wu-zi Hypoglycemic Formula can improveoxidative stress state and regulate inflammation reaction and improve the condition ofinsulin resistance in T2DM model rats.3Wu-zi Hypoglycemic Formula can improve thecondition of insulin resistance in T2DM, which is related to the increasing of p-IRS-1(Tyr895)protein level and the decreasing of PTP1B protein level, the increasing of GLUT4protein level in skeleton muscle.4Wu-zi Hypoglycemic Formula can improve thecondition of insulin resistance in T2DM, which is related to the increasing of liverglycogen content, AKT and GSK-3β phosphorylation at serine473and serine9respectively in liver. |
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