Based On TLRS Signaling Pathway And Insulin Signaling Pathway, Explore The Therapeutic Effect Of Mulberry Leaf On T2DM And Its Mechanism

Background:Type 2 diabetes mellitus(T2DM)is a non-infectious disease characterized by disorders of glycolipid metabolism.Because of the diverse pathogenic factors and complex pathological mechanisms,T2DM has become one of the major diseases that plague and endanger mankind health.In recent years,with clinical and experimental research on diabetes,scholars believe that T2DM is a chronic inflammatory disease associated with metabolic disorders.Clinical practice has found that inflammatory factors are highly expressed in patients with T2DM,and experimental data also indicate that secretion of inflammatory factors is an important factor leading to T2DM.Clinical treatment of T2DM is mainly based on chemical drugs.Although the curative effect is significant and often accompanied by certain side effects,it is urgent to find new drugs for treating T2DM.More than 2000 years ago,Chinese traditional medicine(TCM)recorded the symptoms of diabetes-like diseases.TCM believes that T2DM belongs to the category of"thirst quenching" or "eliminating".Most of the patients become diabetic because of intemperate diet and high-calorie food.For different pathogenesis of diseases,Chinese medicine often uses different drugs to treat T2DM.The mulberry leaves,one of the heat-clearing drugs,is commonly used traditional Chinese medicines for treating T2DM.Pharmacological studies have shown that mulberry leaves contain various hypoglycemic substances,which can improve the body's glucose metabolism in many ways.Other studies have also found that mulberry leaves can inhibit the inflammatory response of various animal models,but there are few reports on whether mulberry leaves could treat T2DM by inhibiting inflammatory response.Therefore,this article will study whether mulberry leaves can improve T2DM symptoms through inflammatory pathways.which could provide ideas and basis for the development of new role of traditional Chinese medicine.Methods:In this experiment,SPF-class Wistar male rats were selected as experimental animals.After feeding for 10 weeks with high-sugar and high-fat diet,low-dose streptozotocin was intraperitoneally injected.Rats with fasting blood glucose ?12mmol/L were selected for the experiment,continued high-calorie feed,and administrated with water extract of mulberry leaves for 12 weeks.During the experiment,the basic pharmacodynamics index,body weight and water intake of the rats were measured weekly,and the fasting blood glucose of the rats was measured weekly.At the 11th week,the oral glucose tolerance test was measured in rats.The last week of the experiment,the insulin tolerance test(ITT)of the rats was measured.At the end of the experiment,the serum insulin content,TNF-±,IL-6 and CRP levels and blood lipid levels were determined.The above indicators were used to comprehensively evaluate the efficacy of mulberry leaves in T2DM rats.On this basis,Conduct a mechanism discussion.Rat liver and muscle tissues were selected for pathological examination.The expression of TLR7-9 mRNA in rat liver tissue and the expression of TLR1-2 mRNA in rat skeletal muscle and mRNA expression in insulin signaling pathway in rat adipose tissue were determined by PCR.the amount.Western-blot was used to determine the expression levels the downstream signaling proteins of the TLRs in the liver and muscle tissues,MyD88 TRAF6,NF-?B,and the expression of InsR,IRS1,PI3K and GLUT4 in adipose tissue.Results:Pharmacodynamic experiments showed that the fasting blood glucose of the mulberry-treated group was not significantly decreased in the early stage of the experiment,but the blood glucose was significantly decreased at the 8th week and the 10th,11th,and 12th week(p<0.01).OGTT showed that high dosage of mulberry leaves could decrease blood glucose and decrease AUC(p<0.01)in rats after glucose gavage.High dosage of mulberry leaves could improve insulin resistance and reduce HOMA-IR in rats,which was statistically significant.(p<0.01);Serum biochemical analyzer showed that the serum levels of TC and LDL-C in the high dosage group of mulberry leaves decreased significantly,which was statistically significant(p<0.05).And,mulberry leaves could reduce the levels of CRP and IL-6 of rats(p<0.01).However,the tendency of mulberry leaves to inhibit the weight loss of T2DM rats was not significantly,and there was no statistical significantly.After the mulberry leaves were given,the food intake and water consumption of T2DM rats only showed a decreasing trend,which was not statistically significant.In the mechanism study,mulberry leaves can improve the liver and muscle pathological structure of T2DM rats.PCR results show that mulberry leaves can significantly reduce the relative expression of TLR7-9 mRNA in liver of T2DM rats(p<0.01),and reduce rat muscle TLR1-2 mRNA expression(p<0.05);up-regulated the expression of InsR,IRS1,PI3K and GLUT4 mRNA in insulin signaling pathway in rat adipose tissue(p<0.05);Western-blot assay showed that mulberry leaves could decrease the expression of MyD88,TRAF6 and NF-?B in liver and muscle tissues of T2DM rats;up-regulate the expression of InsR,IRS1,PI3K and GLUT4 insulin signaling pathway proteins in rat adipose tissue(p<0.05 or p<0.01).Conclusion:Mulberry leaves can improve glucose metabolism in T2DM rats,improve glucose tolerance and improve insulin resistance in rats.Mulberry leaves can improve blood lipid metabolism in T2DM rats and inhibit the expression of inflammatory factors in serum.Mulberry leaves inhibit inflammatory factors.The expression is to inhibit the expression of TLRs and reduce the expression of downstream signaling pathway proteins;mulberry leaves can up-regulate the expression of insulin signaling pathway proteins and improve T2DM.In summary,mulberry leaves can improve insulin resistance and alleviate T2DM symptoms by improving inflammation.