| Background:A large epidemiological data shows that the occurrence and the development of insulin resistance(IR) was closely related to those of type2diabetes, and so did it between insulin receptor substrate (IRS) and insulin resistance. IRS-1and IRS-2are two main kinds of insulin receptors of the substrate. Researches found that IRS-2/PI-3K signal was the main signal transduction pathway during the process of insulin effects on liver physiology. IRS-2signal turned to be abnormal especially for the defects of receptors and after the receptor level is closely related to the insulin resistance in liver. Insulin receptor and IRS-2are core molecules in liver insulin-signaling transmission. The change of any signal molecules on the signal network will lead liver insulin-signaling transmission ability to abate, and cause insulin resistance.Some researches have shown that astragalus polysaccharides(APS)can improve insulin resistance. But whether the APS can improve liver insulin resistance through its effects on InsR、IRS-2in the liver should be studied furtherly.Objectives:To establish obesity insulin resistance model in rat and to observe the influences of APS on protein expression of InsR, and IRS-2in the liver. Try to explore the mechanism of APS and to reduce insulin resistance in the type2diabetic model rat so as to provide evidence for the treatment.Methods:60healthy male Sprague-Dawley rats weighting about240-260g were housed in an environmentally controlled room and after accustomed for one week, they were randomly divided into two groups:the normal controlled group (NC group, n=10) and the high fat model group (HFM group, n=50). The NC group was fed on a standard diet and the high fat model group was given high fat diet. After feeding for6weeks, the rats’ weight in high fat group increased significantly and was20%heavier than those in normal controlled group. Six weeks later, high fat model group rats were injected with Streptozotocin(STZ,25mg/kg). The rats whose blood glucose was more than16.7mmol/l were identified as diabetes mellitus models after72h. We dtected the random blood glucose after intraperitoneal injection with STZ for two weeks, and excluded the rats with blood glucose under16.7mmol/l. Then the type2diabetic model rats were divided randomly into three groups:diabetic model controlled group(DMC group, n=13), pioglitazone group(Pio group, n=13), and APS group(APS group, n=13). Pioglitazone and APS were separately administrated. The normal group, and diabetic model controlled group were treated with saline. After intervention for four weeks, the blood sample was llected by cardiac puncture after given intraperitoneal anesthesia for the biochemical analysis. The rats’ liver tissue was collected to observe histological changes by HE and to determine the expression of InsR and IRS-2protein. Then analysed the correlation of these datas. All datas were reported by the way of "mean±standard deviation". SPSS16.0statistics software was adopted for analysis of these datas, and analysis of variance and linear correlation. P<0.05was considered statistically siginificant.Results:1. Compared with the normal controlled group, the weight of high fat model group increased20%heavier and showed obvious obesity at the sixth weekend(P<0.05). The random blood glucose of high fat model group rats was higher than that of NC group, but there was no statistic difference between the two groups(P>0.05). The random blood glucose level of high fat model group rats increased after injection of STZ (P<0.05).2. At the twelfth weekend, compared with normol controlled group, the level of fasting blood glucose, serum triglyceride, cholesterol, fasting insulin and VF/W in diabetic model controlled group, pioglitazone group and APS group were significantly increased(P<0.05) and insulin sensitivity index(ISI) decreased(P<0.05). Compared with the diabetic model controlled group, the levels of fasting blood glucose, Serum triglyceride, cholesterol, FINS and VF/W in pioglitazone group and APS group were significantly decreased(P<0.05) and ISI increased (P<0.05). The levels of these datas in APS group was higher than that of pioglitazone group, but there was no statistic difference between the two goups (P>0.05). Severe liver steatosis was observed microscopically in DMC group (P<0.05), the liver steatosis in pioglitazone group and APS group were milder than that in DMC group(P<0.05). Immunohistochemical detection:compared with normal controlled group, the ratio of the average optica of InsR and IRS-2in DMC, pioglitazone group and APS group were significantly decreased(P<0.05). Compared with the DMC group, the levels of InsR and IRS-2in pioglitazone group and APS group were significantly increased(P<0.05). Compared with pioglitazone group, the levels of InsR and IRS-2in APS group had no significant differences. The correlation analysis showed that the relationship between InsR and FINS, VF/W is negative(r=-0.463,P=0.001; r=-0.410,P=0.005). The relationship between InsR and ISI is positive(r=0.442,P=0.002). The relationship between IRS-2and FINS,VF/W is negaitive(r=-0.813,P=0.000; r=-0.745,P=0.000). The relationship between IRS-2and ISI is posiitive(r=0.550,P=0.000).Conclusions:1. APS can effectively decrease blood glucose and regulate abnormal blood lipid.2. APS can improve insulin resistance, and this may be related to the increasing of the level of InsR and IRS-2. |
PDF Full Text Request