The Mechanism Study Of Ameliorative Effect Of Semen Sojae Preparatum Extract On Insulin Resistance Rats In Type 2 Diabetes Mellitus

Objective: Semen Sojae Praeparatum is a traditional Chinese medicine that fermented with mulberry leaf and sweet wormwood herb from ripe beans, it has the effects of inducing diaphoresis, releasing restlessness and dispelling heat. Our earlier research shows that Semen Sojae Praeparatum has a therapeutic effect of decreasing blood glucose, in order to evaluate the ameliorative effect of Semen Sojae Preparatum extract on insulin resistance rats in type 2 diabetes mellitus further, in our research, we use the methods of feeding high glucose-lipoids animal feeds and injecting low dose streptozotocin intraperitoneally to set up the IR model, observe the effect of Semen Sojae Praeparatum extract on the expression of InsR mRNA and other relative biochemical indicators and investigate possible mechanism.Methods: The model of insulin resistance rats in type 2 diabetes mellitus were induced by feeding high glucose-lipoids animal feeds for 4 weeks and injecting low dose streptozotocin intraperitoneally. Meanwhile, put 10 rats into the control group, fed with normal diet and inject citric acid-citrate sodium buffer intraperitoneally. The fasting plasma glucose (FPG) was measured in rats of the model group, choose 40 rats whose FPG were more than 7.7 mmol·L-1 for the experiment, according to FPG divided them into four groups randomly (10 rats/group), model group, high dose of SSP group (20 g crude drug/kg), low dose of SSP group (10 g crude drug/kg) and Rosiglitazone group (1.8 mg/kg). Glucose tolerance test (GTT) of rats was measured after intervention respectively for 8 weeks, then the FPG, fasting serum insulin (FINS), glycosylated hemoglobin (GHb), tumor necrosis factor-α(TNF-α), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured, insulin sensitivity index (ISI) was calculated; morphology of pancreatic tissue was observed; the expression level of InsR mRNA of liver was determined by used reverse trascription polymerase chain reaction (RT-PCR). We recorded all the datas and analysised them with SPSS 11.5, the datas were expressed with mean standard deviation.Results:1 The effect of SSP extract on GTT of IR ratsThe blood glucose of each group already reached the peak at 0.5 hour. The value of BG and AUC in model group were apparently higher than those in normal group at 0, 0.5, 1, 2 hour respectively (P<0.01); Compared with the model group, the value of BG and AUC in SSP-H and RSG group were apparently lower at 0, 0.5, 1, 2 hour respectively (P<0.01), the value of BG and AUC in SSP-L group were also apparently lower at 0, 1, 2 hour respectively (P<0.05), but had no significant difference at 0.5 hour (P>0.05).2 The effect of SSP extract on FPG, GHb of IR ratsThe FPG and GHb in model group were obviously higher than those in normal group (P<0.01). Compared with the model group, FPG and GHb in both SSP-H and SSP-L groups were obviously lower (P<0.01), moreover, they had some dose-dependent relationships (P<0.05 or P<0.01), SSP-H group was better; the FPG and GHb in the RSG group were also obviously lower (P<0.01).3 The effect of SSP extract on FINS, ISI of IR ratsCompared with the normal group, FINS in model group was obviously higher (P<0.01); ISI was obviously lower (P<0.01). Compared with the model group, FINS in each medication administration group was obviously lower (P<0.01), ISI was obviously higher (P<0.01).4 The effect of SSP extract on TNF-αof IR ratsThe TNF-αin model group was obviously higher than those in normal group (P<0.01). Compared with the model group, TNF-αin each medication administration group was obviously lower (P<0.01).5 The effect of SSP extract on SOD, MDA of IR ratsCompared with the normal group, SOD in model group was obviously lower (P<0.01); MDA was obviously higher (P<0.01). Compared with the model group, SOD in both SSP-H and SSP-L group were obviously higher, MDA was obviously lower, moreover, they had some dose-dependent relationships (P<0.05 or P<0.01), SSP-H group was better; SOD in the RSG group was also obviously higher (P<0.01), MDA was also obviously lower (P<0.01).6 The effect of SSP extract on morphology of pancreatic tissue of IR ratsCompared with the normal group, the quantity of islet cells in model group was obviously lower, the volume of islet cells was decreased, the cytoplasm of some islet cells were vacuolar degenerative, the cell nucleus were pycnotic. Compared with the model group, the pancreatic tissue of the SSP-H, SSP-L and RSG group were more integral, the configuration of islets of langerhans was replete, the border was clear, the quantity of islet cells was obviously higher, the quantity of vacuoles of the cytoplasm were obviously lower, the volume of islet cells was almost normal, SSP-H and RSG group were better.7 The effect of SSP extract on the expression of InsR mRNA in liver of IR ratsThe expression of InsR mRNA in model group was obviously lower than the normal group (P<0.01). Compared with the model group, the expression of InsR mRNA in each medication administration group was obviously higher (P<0.01).Conclusion: SSP extract can increase GTT of insulin resistance rats in type 2 diabetes mellitus which are induced by feeding high glucose-lipoids animal feeds and injecting low dose streptozotocin intraperitoneally. SSP extract also can decrease the level of FPG, GHb and FINS, increase the numerical value of ISI, protect beta cell of islet, improve the sensitivity of insulin, ameliorate glycometabolism, ameliorate insulin resistance, the possible mechanism are:1 Up-regulate the expression of InsR mRNA in liver;2 Decrease the level of serum TNF-α;3 Heighten the level of serum SOD, decrease the level of serum MDA, confront oxidative stress.