RESUMO
Objective:To investigate the role of stress-inducible protein Sestrin2 (Sesn2) in the improvement of insulin resistance in rat L6 skeletal muscle cells treated with liraglutide.Methods:The establishment of insulin resistance model of rat L6 skeletal muscle cells was induced by palmitate. The experimental cells were divided into control group(Con group), palmitate 0.6 mmol/L treatment group(PA group), palmitate 0.6 mmol/L+ liraglutide 10 nmol/L treatment group(PA+ Lir10 group), palmitate 0.6 mmol/L+ liraglutide 100 nmol/L treatment group(PA+ Lir100 group), and palmitate 0.6 mmol/L+ liraglutide 1 000 nmol/L treatment group(PA+ Lir1000 group). The cell counting kit 8(CCK8) method was used to detect the cell activity in each group. Western blotting was used to detect the expression levels of glucose transporter 4(GLUT4), protein kinase B(Akt), phosphorylated protein kinase B(p-Akt), and Sesn2 protein in L6 cells. L6 cells were transfected with siRNA to inhibit the expression of Sesn2. The cells were treated with palmitate and liraglutide. Western blotting was used to detect the expression levels of Sesn2, Akt, p-Akt, and GLUT4 protein in L6 cells.Results:Compared with Con group, the cell survival rate, p-Akt/Akt ratio, Sesn2, and GLUT4 protein expression in PA group decreased significantly( P<0.05). After liraglutide intervention, the cell activity, p-Akt/Akt ratio, Sesn2, and GLUT4 protein expression of PA+ Lir100 and PA+ Lir1000 groups was increased( P<0.05). After inhibiting the expression of Sesn2, p-Akt/Akt ratio and GLUT4 protein in transfected si-Sesn2 and treated with 0.6 mmol/L palmitate group(PA+ si-Sesn2 group) and transfected si-Sesn2 and treated with 0.6 mmol/L palmitate+ liraglutide 100 nmol/L group (Lir100+ PA+ si-Sesn2 group) were significantly lower than those in transfection negative group (si-Con group; P<0.05). Even after liraglutide intervention, compared with PA+ si-Sesn2 group, p-Akt/Akt ratio and GLUT4 protein expression level were not significantly increased in Lir100+ PA+ si-Sesn2 group ( P>0.05). Conclusions:Palmitate could induce the decrease of p-Akt/Akt ratio and GLUT4 protein expression in L6 cells. Liraglutide upregulates the expression of Sesn2, which leads to the increase of p-Akt/Akt ratio and GLUT4 protein expression and contributes to the improvement of insulin resistance.
RESUMO
Objective:To explore the characteristics of intestinal flora in female patients with type 2 diabetes mellitus (T2DM) with comorbid coronary heart disease.Methods:Female patients with T2DM from September 2019 to November 2020 were enrolled in this study and divided into 2 groups stratified by coronary heart disease: 22 patients with coronary heart disease(T2DM+ CHD group) and 49 patients with simple T2DM group(T2DM group). Thirty-one healthy females were selected as the normal control group(NC group). The abundance of intestinal flora, the difference in intestinal flora and its relationship with indicators such as glycosylated hemoglobin and fasting blood glucose was analyzed by the real-time fluorescent quantitative PCR detection technology in the three groups.Results:The abundance of Prevotella in the T2DM group was lower, and Roseburia inulinivorans and Faecalibacterium prausnitzii in the T2DM+ CHD group were lower, while Bacteroides and Enterococcus spp in the T2DM+ CHD group were higher compared with NC group, respectively( P<0.05). The abundance of Bacteroides and Enterococcus spp in the T2DM+ CHD group was lower than that in the T2DM group( P<0.05). Spearman correlation analysis showed that the abundance of Faecalibacterium prausnitzii and Eubacterium rectale was negatively correlated with obesity while abundance of Bacteroides and Enterococcus spp was positively correlated with HbA 1C and fasting blood glucose. The abundance of Bacteroides was positively correlated with TCH and TG(all P<0.05). Logistic regression analysis showed that Bacteroides and Enterococcus spp were independent influencing factor of the development of female patients with T2DM and CHD. Conclusion:Female T2DM and T2DM with CHD had intestinal flora imbalance, which was related to a variety of glucose and lipid metabolism indicators, and might be closely related to the occurrence of T2DM and CHD. Bacteroides and Enterococcus spp were independent influencing factors of the development of female patients with T2DM and CHD. Regulating the intestinal flora can provide ideas for the prevention and treatment of T2DM with CHD in female.