ABSTRACT
Objective:To explore the effect of recombinant human syntaxin-4(STX4) on lipopolysaccharide(LPS)-induced injury in islet β-cells(INS-1).Methods:Pancreatic islet β-cells(INS-1) were divided into Control (blank control), LPS (LPS treatment), LPS+ NC (transfection of negative control vector, LPS treatment), and LPS+ STX4 (transfection of pcDNA-STX4, LPS treatment) groups. RT-qPCR and Western blot were used to detect STX4 mRNA and protein expression, flow cytometry to detect apoptosis, DCFHDA method to detect reactive oxygen species(ROS) level, xanthine oxidation method to detect superoxide orgotein dismutase(SOD) level, colorimetric method to detect glutathione peroxidase(GSH-Px) level, ammonium molybdate colorimetric method to detect catalase(CAT) level, thiobarbituric acid method to detect malonaldehyde(MDA) level, ELISA method to detect the level of interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and insulin secretion levels under glucose conditions secreted by cells, Western blot method to detect Cleared Caspase-3, Bcl-2 Associated X Protein(Bax), p65 protein expression. After treatment with NF-κB signaling pathway activator, STX4 up-regulated islet β-cell INS-1 was given LPS stimulation, and the same method was used to measure apoptosis, ROS, SOD, GSH-Px, CAT, MDA levels and secreted IL-1β, TNF-α, insulin levels and Cleaved Caspase-3, Bax, p65 protein levels.Results:Compared with the Control group, the expression of STX4 mRNA and protein in islet β cells of the LPS group decreased, the apoptosis rate, ROS level, and MDA levels increased, and the levels of SOD, GSH-Px, and CAT decreased, the levels of IL-1β, TNF-α increased, the level of insulin secreted by the cells decreased, and the expression levels of Cleaved Caspase-3, Bax, and p65 also increased. NF-κB pathway activator treatment reversed the effect of up-regulated STX4 on islet β-cell apoptosis, ROS, SOD, GSH-Px, CAT, MDA levels and secreted IL-1β, TNF-α levels, and Cleaved Caspase-3 , Bax and p65 protein levels.Conclusion:Up-regulation of STX4 alleviated LPS-induced islet β cell oxidative damage, apoptosis and inflammatory factor release. The underlying mechanism might be related to the inhibition of activated NF-κB signaling pathway.
ABSTRACT
Objective To explore the relationship between fibroblast growth factor 21(FGF21) and islet β cell function in pregnant women with different glucose tolerance status.Methods A total of 441 pregnant women were selected in this study from our hospital.Their 50 g GCT at 24~28 gestational weeks were all positive.One week later,all the subjects were treated with 75 g OGTT,and divided into three groups according to their test results:GDM group (n=228),GIGT group (n=112) and GNGT group (n=91).Serum FGF21 level was tested by ELISA.Islet β cell function was evaluated by HOMA-IR,ISI-Matsuda,HOMA-IS,Stumvoll first,second phase secretion and ISSI.The correlation between FGF21 and islet β cell function was evaluated by Pearson correlation analysis.Results (1) BMI,0 h,1 h,2 h,3 hPG and 1 h,2 h,3 hIns were higher in GDM group and GIGT group than in GNGT group,and highest in GDM group (P0.05).(3)Pearson correlation analysis showed that FGF21 was positively correlated with HOMA-IR(r=0.255,P=0.030) and was negatively correlated with ISI-Matsuda,HOMA-β,Stumvoll first,second phase secretion and ISSI(r=-0.289,-0.256,-0.224,-0.230,-0.277,P=0.019,0.037,0.045,0.040,0.023).Conclusion Along with the worsening of glucose metabolic damage,the FGF21 level is increased gradually.FGF21 is related to islet β cell function,and may enroll in the occurrence and development of GDM.
ABSTRACT
Objective:To investigate the efficacy and safety of insulin glarsine combined with sitagliptin in elderly type 2 diabetic patients whose blood glucose levels were inadequately controlled by oral anti-diabetic drugs ( OAD) . Methods: In the open-labeled, randomized and parallel study, 98patients (≥60 years) were randomly divided into two groups: insulin glargine/sitagliptin combina-tion group (n=52, the observation group ) and insulin Aspart 30 injection group (n=46, the control group). The dose was adjusted according to the blood glucose. The fasting blood glucose (FBG), 2h postprandial blood glucose (2hPBG), glycosylated hemoglobin (HbA1c), the incidence of hypoglycemia and body mass index (BMI) after the 12-week treatment were compared between the two groups. Results:The fasting glucose and the incidence of hypoglycemia in the observation group were lower than those in the control group (P0. 05). Conclusion:The treatment of insulin glargine combined with sitagliptin is safe, effective and convenient in elderly type 2 diabetes patients with poor glycemic control. By diabetic education, the lower incidence of hypoglycemia treatment will be a better choice for elderly type 2 diabetic patients.