Mechanism Of Akkermansia Muciniphila Improving Skeletal Muscle Insulin Resistance In Obese Mice

Type 2 diabetes is complicated by genetic and environmental factors,making type 2 diabetes a major public health problem facing the world.The relationship between type 2 diabetes and obesity is based on insulin resistance caused by obesity[,].Skeletal muscle insulin resistance plays an important role in systemic insulin resistance.Under normal conditions,skeletal muscle is the most important organ for maintaining systemic glucose homeostasis.[2,3].Skeletal muscle is responsible for approximately 80%of the body's insulin-stimulated systemic glucose intake and consumption.[4,5].More importantly,skeletal muscle insulin resistance occurs much earlier than the clinical stage of type 2 diabetes caused by insulin resistance.Hyperglycemia and beta cell failure occur only after decades of skeletal muscle insulin resistance in the body[12].Therefore,early detection of skeletal muscle insulin resistance and intervention can play an important role in the prevention and treatment of type 2 diabetes.The researchers found that the mucus-decomposing bacteria Akk in the intestinal tract is closely related to insulin resistance.Akk was negatively correlated with fasting blood glucose in the subjects,and insulin resistance in mice treated with Akk was improved compared to the control group[12].So Akk has a positive effect on improving insulin resistance.At the same time,Akk can improve the function of the intestinal barrier,reduce the entry of LPS into the circulation,and alleviate the endotoxemia induced by high-fat diet.LPS can activate TLR4,and the activation of TLR4 is an important factor in the development of insulin resistance[12].Therefore,we hypothesize that Akk may alleviate insulin resistance in obese individuals by mitigating inflammatory responses in skeletal muscle,which provides a new approach to the prevention of type 2 diabetes.1.Objectives:1.1 To investigate whether Akk can improve obesity-induced insulin resistance.1.2 To explore the mechanism of Akk improving insulin resistance in skeletal muscle of obese mice.2.Methods2.1 animals and grouping40 C57BL/6 male mice were randomly divided into 4 groups,which were:high fat diet + Akk group,high fat diet + PBS group,normal diet + Akk group,normal diet +PBS group.In Akk group,givenl.4 × 109CFU/0.2ml/only/day dose of gavage,the control group given the same volume of PBS gavage.The entire experiment lasted 12 months.2.2 Fasting blood glucose and oral glucose tolerance test was measured in mice.2.3 Detection of the concentration of free fatty acids in the serum of mice.2.4 Detection of free fatty acid content in mouse muscle tissue.2.5 Detection of IL-6,IL-10 and TNF-a in muscle tissue of mice.3.Results:3.1 Akk is able to alleviate obesity-induced insulin resistance.3.2,Akk did not alleviate the weight gain of mice on a high-fat diet.3.3 Akk did not reduce the amount of free fatty acids in serum and muscle tissue.3.4 Akk can reduce the pro-inflammatory cytokine TNF-a in muscle tissue.4.Conclusion:4.1Akk relieves obesity-induced insulin resistance may not by weight loss.4.2 Akk may not be relieve skeletal muscle insulin resistance by lowering serum free fatty acids.4.3Akk is able to alleviate the inflammatory state of muscle tissue by reducing some of the pro-inflammatory cytokines.