The Mechanism Of Liraglutide Improving Insulin Resistance Of Skeletal Muscle Induced By High Fat

Objective:In this paper,high-fat induced mice were used as research objects,and their body weight,blood glucose,insulin,IL-1,IL-6,galanin and other indicators were measured to explore the role and mechanism of liraglutide in reducing insulin resistance in type 2 diabetes.(1)To explore the effects of liraglutide on the metabolism of insulin-resistant mice through animal model experiments.(2)To investigate the effect of liraglutide on skeletal muscle GLUT4 and its related signals in the periphery to improve skeletal muscle insulin sensitivity.(3)To explore the mechanism of liraglutide’s central role in improving insulin resistance by inhibiting galanin.Methods:Twenty-four healthy male mice aged 7-8 weeks(C57 BL/6 mice,purchased from the Comparative Medical Experiment Center of Yangzhou University)were randomly selected,and eight were randomly selected as normal control groups(NC group n=8)for standard feed feeding.The remaining mice were fed with high-fat diet for 12 weeks,and weighed at a fixed time every week.The mice with a weight of>35g were tested for glucose tolerance.The mice with abnormal glucose tolerance were selected as insulin resistant mice.The model mice were randomly divided into two groups,model control group(OC group n=8)and liraglutide group(Liraglutide group n=8).Liraglutide was added with 100ug physiological saline at 400ug/kg/d.In the model control group,physiological saline was injected intraperitoneally for 7 days.Monitor body weight and food intake every day during the experiment,monitor body weight and fat weight after the experiment,measure fasting blood glucose and glucose tolerance with a fast blood glucose meter,measure plasma insulin,IL-1,IL-6 and irisin by ELISA method;Western-blot test bone Expression of muscle GLUT4 and its related signal proteins;Real-Time PCR method was used to detect the expression of GAL and GALR1 mRNA in hypothalamus.Results:(1)Compared with the model control group,the liraglutide group had significantly lower body weight and fat weight(P<0.05),and the food intake of the mice was significantly reduced(P<0.01).In addition,compared with before the experiment After the liraglutide experiment,the body weight of the mice decreased significantly(P<0.01).It is suggested that liraglutide can reduce fat accumulation,suppress appetite and reduce body weight in insulin resistant mice.(2)Compared with the model control group,the liraglutide group had significantly lower blood glucose and insulin(P<0.01),and significantly increased glucose and insulin tolerance(P<0.01).In addition,compared with before the experiment,the blood glucose of mice after the liraglutide experiment was significantly reduced(P<0.01).It is suggested that liraglutide can improve systemic glucose metabolism and insulin sensitivity in insulin-resistant mice,inhibit insulin secretion and lower blood sugar in insulin-resistant mice.3)Compared with the model control group,the plasma IL-1 and IL-6 decreased significantly in the liraglutide group(P<0.01),and irisin increased significantly(P<0.05).It is suggested that liraglutide inhibits the secretion of inflammatory factors in insulin-resistant mice and increases the expression of muscle protective factors,thereby improving systemic glucose metabolism and insulin sensitivity.(4)Compared with the model control group,the liraglutide group’s skeletal muscle GLUT4,SIRT1 and PGC-1α protein levels were significantly increased(P<0.05).It is suggested that liraglutide mainly reduces insulin resistance by increasing the expression of GLUT4,SIRT1 and PGC-1α in skeletal muscle of insulin resistant mice.(5)Compared with the model control group,the liraglutide group had significantly lower levels of GAL and GlALR1mRNA in the hypothalamus(P<0.05).It is suggested that liraglutide mainly reduces insulin resistance by reducing the expression of GAL and G1ALR1 mRNA in the hypothalamus of insulin resistant mice.Conclusion:Liraglutide inhibits high-fat induced insulin resistance in mice with appetite,reduces fat accumulation,and reduces body weight.Liraglutide improves glucose metabolism in high-fat induced insulin-resistant mice and increases skeletal muscle insulin sensitivity.Liraglutide inhibits high-fat Induce secretion of inflammatory factors in mice with insulin resistance.Liraglutide may increase the insulin sensitivity of skeletal muscle by activating SIRT1/PGC-1a/GLUT4 signaling pathway and reducing central galanin expression.