| Objective:To evaluate the hypoglycemic effect of sitagliptin on newly diagnosed type 2 diabetes patients in the first affiliated hospital of xinjiang medical university.To explore the reasons for the difference in hypoglycemic efficacy of sitagliptin in the newly diagnosed type 2 diabetes,screen the differential genes and verify the differential genes by fluorescence quantitative PCR.Further,the mechanism of the hypoglycemic effect of sitagliptin was explored through the in vitro insulin resistance cell model to provide scientific basis for guiding rational and effective drug use in patients with diabetes.Methods:This is a randomized controlled study,from March 2016 to December 2018,232 newly diagnosed patients with type 2 diabetes in the department of endocrinology of the first affiliated hospital of xinjiang medical university and the physical examination center of the largest affiliated medical department of the XJ medical university were selected and divided into the sitagliptin treatment group and the metformin treatment group.The subjects' personal and past histories were collected measuring the corresponding weight information,height value,hip circumference value and other indicators,and their glucose metabolism,lipid metabolism,neck intima and fatty liver were tested.SPSS22.0 was used for data processing and statistical analysis.Continuous variables were described by mean ± standard deviation,the comparative analysis between different groups needs to complete the corresponding sample t test and control sample t-test was used for intra-group comparison.The classified variables were described by frequency and percentage,and the chi-square test or Fisher's exact probability method were used for statistical inference.Binomial logistics regression was used to analyze the influencing factors,and the model selection method was regressive method(LR).P<0.05 was considered statistically significant.To analyze the difference of general information and clinical indicators in patients with diabetes of different genders,and to compare the hypoglycemic effect of sitagliptin and metformin on newly diagnosed type 2 diabetes and related clinical indicators.Then in sitagliptin treatment group of 30 to 40 years old of age,gender,age matched in 8 patients with glycosylated hemoglobin after treatment by<0.4%poor groups,the curative effects by>0.9%for curative effect is distinct groups,each group of 4 cases(male 2 female)to transcriptome high-throughput gene sequencing found differences,poor curative effect after extraction,the curative effect is distinct group,a total of 40 patients with gender,age matched(20 cases in each group)according to the differences of high-throughput sequencing found gene RT-PCR verification.Again by establishing the cell model in vitro insulin resistance,by setting the different groups,to observe the insulin resistance cell model,SOCS3 silence,sitagliptin treatment group and SOCS3 silence + sitagliptin treatment group influence on glucose consumption and the content of glycogen,qRT PCR detection of SOCS3,AKT,GSK-3 beta gene expression level,WB SOCS3 and AKT,p-AKT,GSK-3 beta,p-GSK-3 beta protein expression levels,So as to explore the mechanism that affects the hypoglycemic effect of sitagliptin.Results:1.Analysis of the hypoglycemic effect of sitagliptinFor newly diagnosed type 2 diabetes,glycosylated hemoglobin,glycosylated serum protein,fasting blood glucose,2-h postprandial blood glucose,triglyceride and urea nitrogen were all lower after treatment than before treatment.After metformin treatment,hba1 c,fasting blood glucose,2h postprandial blood glucose,insulin,homaIR,triglyceride,direct bilirubin,indirect bilirubin,creatinine,and estimated glomerular filtration rate were all lower than before treatment,and high-density lipoprotein was higher than before treatment.After 3 months of monotherapy,the effect of sitagliptin group on 2h postprandial blood glucose control was better than that of metformin group,and the glycated hemoglobin,total bilirubin,indirect bilirubin and aspartic aminotransferase(U/L)in the sitagliptin group were all higher than that in the metformin group.Among patients with type 2 diabetes who had no difference in baseline hba1 c,there was an individual difference in hba1 c reduction 3 months after treatment with sitagliptin,characterized by a relatively significant decrease in hba1 c in patients with a lower bmi.It indicates that the hypoglycemic effect of siglitine is different in different diabetes patients.2.Transcriptome high-throughput sequencing and rt-pcr validation results of patients with different efficacy of sitagliptineThree months after treatment with sitagliptin,high-throughput sequencing of transcriptome revealed that there were different genes in the groups with significant hypoglycemic effect and those with poor efficacy: GHRL,IGF1 R,MAPK3,PIK3 CD and SOCS3.Rt-pcr verification: there was no difference in GHRL gene between the groups with significant and poor efficacy of sitagliptin.IGF1 R gene expression was significantly increased with a P value of 0.034,MAPK3 expression was significantly decreased with a P value of 0.002,and SOCS3 gene expression was significantly decreased with a P value of 0.000.The expression of PIK3 CD decreased,but there was no difference.3.In vitro insulin resistance cell model to analyze the mechanism of sitagliptin 's effect on diabetes through SOCS3/PI3K/AKT pathwayThe expression of SOCS3 gene was significantly increased in the insulin resistance model group and the insulin resistance model + sirna-nc group,and decreased after the intervention of the drug sitagliptin.In the model group,AKT was not significantly changed by qrt-pcr,while the expression of AKT,p-akt and p-gsk-3 protein was significantly decreased.After drug intervention or silencing of SOCS3,SOCS3 protein was significantly reduced,indicating that sitagliptin could improve insulin resistance and play a hypoglycemic role by down-regulating SOCS3 level.Conclusion:1.The effect of sitagliptin group on 2h postprandial blood glucose control was better than that of metformin group,and the glycated hemoglobin,total bilirubin,indirect bilirubin and aspartic aminotransferase in the sitagliptin group were all higher than that in the metformin group.Blood glucose and blood lipid levels in the sitagliptin group were lower after treatment than before treatment.Blood glucose,insulin resistance and blood lipid in metformin group improved after treatment.Among patients with type 2 diabetes who had no difference in baseline hba1 c,there was an individual difference in hba1 c reduction 3 months after treatment with sitagliptin,characterized by a relatively significant decrease in hba1 c in patients with a lower bmi.It indicates that the hypoglycemic effect of sitagliptin is different in different diabetes patients.2.IGF1 R gene expression was significantly increased,MAPK3 expression was significantly decreased and SOCS3 gene expression was significantly decreased in the sitagliptin treatment group.3.In vitro insulin resistance cell model,it was found that the expression of SOCS3 gene was significantly increased in the insulin resistance model group and the insulin resistance model + sirna-nc group,and decreased after the intervention of the drug sitagliptin.The expression of AKT,p-akt and p-gsk-3 beta proteins was significantly decreased in the model group.After intervention or silencing of SOCS3 by siglitine,SOCS3 protein was significantly reduced,indicating that sitagliptin could improve insulin resistance and play a hypoglycemic role by down-regulating SOCS3 level. |
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