Effect Of Chitosan Oligosaccharide Guanidine On The Activity Of Related Signal Factors Involved In Glucose Metabolism In Type 2 Diabetic Rats

Type 2 diabetes mellitus(T2DM)is an endocrine disorder characterized by insulin resistance,which leads to disorders of glucose metabolism,leading to long-term hyperglycemia.Studies have shown that about 80% of the body by the insulin-mediated glucose transport and utilization is done by the skeletal muscle,therefore,to promote skeletal muscle cell glucose metabolism can enhance the body’s sensitivity to insulin and prevent the occurrence of metabolic diseases.Moreover,under the condition of hyperglycemia,abnormal glucose metabolism can promote the synthesis and accumulation of DAG,thereby activating the DAG-PKC pathway and accelerating the activation of PKC-β.The activation of PKC-β and its expression of the intracellular transforming growth factor(TGF-β)can increase the expression of extracellular matrix such as fibronectin(FN).In view of this,this paper takes COSG as the objectives,we further clarify the role of COSG in the regulation of GLUT4 in skeletal muscle of type 2 diabetic rats and its regulation on glucose metabolism and explore the effect of COSG on DAG/PKC signaling pathway.Firstly,chitosan oligosaccharide guanidine hydrochloride was prepared by chemical method with chitosan and dicyandiamide as raw materials with molecular weight of 1500 Da and 3000 Da respectively.The effects of molar ratio of reactants,reaction time and pH value on the degree of substitution were investigated.The basic structure of the product was determined by infrared spectroscopy and nuclear magnetic analysis.Secondly,a STZ-induced diabetic rat model was established,and the effects of COSG on fasting blood glucose(FBG),fasting serum insulin and muscle glycogen levels in T2 DM rats were investigated using methyl chitosan and chitosan oligosaccharide as control.Then,we detected the contents of p38 MAPK,P-p38 MAPK,P-IRS,Akt,P-Akt,GLUT4,GLUT4,PKC-β,TGF-β protein,phosphoenolp yruvate carbox ykinase(PEPCK)and glucose-6-phosphate dehydrogenase(G6P).And then we analyzed the key signaling pathways that play a key role.Experimental results show these: After treatment with COSG,the contents of P-p8 MAPK,G6P,PEPCK,DAG,PKC-β,TGF-β and FN in T2 DM rats decreased,and the contents of P-IRS1(Tyr),Akt,membrane GLUT4,and muscle glycogen increased.Analysis of the impact of signal factors on the level of signal,in skeletal muscle tissue,COSG improved the phosphorylation of IRS1 tyrosine site by inhibiting the activation of p38 MAPK,so that the phosphorylation rate of Akt increased.On the one hand,this could increase the membrane conversion ratio of GLUT4 and increase the glucose uptake of skeletal muscle cells,on the other hand,this could inhibit the expression of PEPCK and G6 P,and improve the peripheral insulin sensitivity,thereby inhibiting gluconeogenesis;Eventually,the blood glucose levels in skeletal muscle tissue decreased.In renal tissue,the treatment of COSG decreased the level of hyperglycemia,and then decreased the content of DAG.Furemore,the activity of DAG/PKC signaling pathway was inhibited,which reduced the expression of FN and alleviated the diabetic complications in the kidney.