RESUMO
Objective:To explore the effect of Shenqi compound on islet β-cell function in type 2 diabetic GK rats. The whole genome expression profile chip technology is used to explore the molecular mechanism of Shenqi compound regulating pancreatic islet cell function and provide theoretical basis for the prevention and treatment of type 2 diabetes with traditional Chinese medicine. Method:GK rats were fed with high-fat diet daily for 4 weeks. Rats were randomly selected from GK rats to detect random blood glucose and verified the success of type 2 diabetes model. Rats were divided into 4 groups， Wistar group， model group， Shenqi compound（1.44 g∙kg-1） group and west glenn（16 mg∙kg-1） group. After 8 weeks of gavage， the serum insulin（INS） levels were detected by enzyme-linked immunosorbent assay（ELISA）. The apoptosis of islet β cells was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling（TUNEL）fluorescence method. Differential gene detection uses whole-genome expression profiling chip technology in each group of rat pancreatic tissues， the mRNA transcription level of key differential genes is detected by Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）. Result:Compared with blank group， before gavage， 4 weeks， 8 weeks， GK rats have higher blood sugar in each group （P<0.01）.Gavage for 4 weeks and gavage for 8 weeks， compared with model group， the blood sugar of rats in each drug intervention group was lower （P<0.01）. Gavage for 8 weeks， compared with blank group， the INS level of model group was lower （P<0.01）. Compared with model group， the Shenqi compound group had a higher INS level， and the sitagliptin group had a higher INS level （P<0.01）. After gavage for 8 weeks， compared with the blank group， the number of pancreatic islet β-cell apoptosis in the model group was higher （P<0.05）. Compared with model group， the number of pancreatic islet β cell apoptosis in the Shenqi compound group and sitagliptin group was lower （P<0.05，P<0.01）. Gene chip and Real-time PCR tests both showed that phosphatidylinositol 3-kinase receptor 1（PIK3R1） was up-regulated in the Shenqi compound group/model group， and down-regulated in the sitagliptin group/model group， model group/blank group. Protein kinase B1（Akt1） was expressed in the Shenqi compound group/model The expression was up-regulated in the group， sitagliptin group/model group， and down-regulated in the model group/blank group. Conclusion:Shenqi compound which has the function of supplenmenting Qi and Yin and promoting the blood circulation， can inhibit the islet β cell apoptosis， improve islet β cell function， regulate insulin secretion， and prevent T2DM by up-regulating the expression of genes PIK3R1 and Akt1.
RESUMO
Objective To observe the influence of epalrestat combined with insulin therapy on islet beta cell function in newly diagnosed type 2 diabetic patients.Methods 45 newly diagnosed type 2 diabetic patients were randomly treated with 4 times of subcutaneous insulin therapy(RI group) or epalrestat plus 4 times of subcutaneous insulin therapy(RI + EP group).Patients were followed up for 3 months.The fasting blood-glucose (FPG),the 2 hour postprandial blood glucose (2 h PG),fasting insulin (FINS),the 2 hour postprandial blood insulin (2 h INS),glycated hemoglobin (HbA1 C),superoxide dismutase (SOD),malondialdehyde (MDA),insulin resistance index (HOMA-IR) and insulin release index(HOMA-β) were observed at 3th month after the initiation of therapy.Results Follow-up evaluation of 22 cases in RI group,23 cases in group RI + EP were completed 3 months of treatment.After treatment,FPG,2 h PG,HbA1 C,MDA and HOMA-IR in the two groups were decreased than those before treatment,the serum FINS,2 h INS,SOD and HOMA-β were higher than those before treatment,the differences were statistically significant (all P ＜0.05).After treatment,FINS,2 h INS,SOD and HOMA-β of RI + EP group were higher than those in RI group,MDA was lower than that of RI group,the differences were statistically significant (t =3.228,2.536,3.021,2.343,2.122,all P ＜ 0.05).FPG,2 h PG,HbA1 C,HOMA-IR between the two groups had no significant differences (all P ＞ 0.05).Linear regression analysis showed that HOMA-β was positively correlated with SOD level (r =0.888,r2 =0.783,all P ＜ 0.01).Conclusion The results suggest that epalrestat combined with insulin therapy can inhibit oxidative stress,and improve islet beta cell function in newly diagnosed type 2 diabetic patients,and its clinical effect is better than monotherapy with insulin.