| Objective:This study was to determine the effects of Zhengqing Recipe (ZQR) on hepatic glucose metabolism in STZ induced type 2 diabetic rats fed high-fructose and high-fat diet, and to investigate the underlying molecular mechanism of the effects.Methods:After one week feeding with regular rodent chow, male Wistar rats were fed with high energy diet for one month. The diabetic rats were established by intravenously injection of low dose of streptozotocin(STZ). The diabetic rats were randomly divided into three groups: model group, ZQR group and Metformin group, the ZQR group was given zhenqing recipe extract (26g/kg/d) and the metformin group was given metformin water solution(150mg/kg/d), while the model group was given equal volume distilled water. Rats in normal control group were fed with regular rodent chow, and lavaged with equal volume distilled water. Treated for 8 wk.1.Body weight, the levels of fasting blood glucose(FBG), fasting serum insulin(FINs). Insulin sensitivity index(ISI) was calculated.2. OGTT of every group were detected.3.The expressions of liver Forkhead box (Fox)O1, Phosphoenolpyruvate carboxykinase(PEPCK), Glucose-6-phosphatase(G6Pase) and Glucokinase(GK)mRNA were detected by RT-PCR.4. The expression of FoxO1 protein was detected by Western blot.Results:1. Body weight: after 4 weeks of administration, body weight in model group was increased compared with the normal control group(P<0.01). Body weight in ZQR group and metformin group rats were reduced compared with the model group (P<0.05). After 8 weeks, body weight in model group was significantly increased compared with the normal control group(P<0.01). Body weight in the two treatment group were decreased (P<0.05).2.The levels of fasting blood glucose(FBG), fasting serum insulin(FINs) and ISI: After 4 weeks of administration, rats in ZQR group and metformin group showed significantly decreased FBG and FINs levels(P<0.01). ISI was significantly increased(P<0.01). After 8 weeks of administration, ZQR and metformin were significantly reduced FBG and FINs levels(P<0.01), and increased ISI levels(P<0.01). Compared with 4 weeks administration, FBG in the two treatment groups were significantly decreased(P<0.01); FINs and ISI levels significantly increased (P<0.01 or P<0.05).3. OGTT: after 8 weeks, blood glucose levels at different times in diabetic rats were significantly increased compared with the mordel rats(P<0.01). The highest blood glucose levels were achieved at 60min. After 120 min, blood glucose levels in the two treatment groups were significantly decreased compared with 60min(P<0.01).4.The expressions of FoxO1, PEPCK, G6Pase and GK mRNA levels in liver: compared with the normal control group, a significant elevated in the expression levels of FoxO1, PEPCK and G6Pase mRNAs was detected in untreated diabetic rats(P<0.01); in contrast, GK mRNA was decreased(P<0.01). Compared with the model group, animals treated with ZQR and Metformin resulted in significant reduction in the relative levels of FoxO1, PEPCK and G6Pase mRNAs, and augmentation in GK mRNA(P<0.01).5.The expression of FoxO1 protein in liver: protein expression of FoxO1 in the model group was markedly increased compared with controls(P<0.01). Consistent with the data of FoxO1 mRNA, reduction in hepatic FoxO1 protein content was detected in the ZQR and Metformin treated rats(P<0.01).Conclusion:High glucose and high fat induce the expression of FoxO1 and its target genes in 2 type diabetic Rats. ZQR treatment reduced FBG and FINs levels, increased insulin levels in STZ induced type 2 diatetic rats fed with high-fructose and high-fat diet.The underlying molecular mech-anism of the effects was associated with down-regul ation of FoxO1, PEPCK and G6Pase expressions leading to reduced hepatic gluconeogenesis, and up-regulation of GK expression resulting in increased hepatic glucose utilization. |
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