Microwave-assisted Synthesis Of Chitooligosaccharide Biguanidine And Its Repairment Effect On Islet ? Cells Of T2DM Rats

Diabetes is a disorder of glucose and lipid metabolism caused by various causes,of which 90%-95% are type 2 diabetes(T2DM).It is characterized by insulin resistance in the peripheral tissues and stable homeostasis in glucose.Studies have shown that islet ?-cell damage and defects are leading to the development of diabetes.Therefore,repair damaged islet ? cells,is the key to the treatment of type 2 diabetes.By reference to the molecular structure of metformin(an oral hypoglycemic drug),chitooligosaccharide guanidine(COSG)and chitosan guanidine(CS)were synthesised by microwave irradiation.Then the insulin resistance model of HepG2 cells(IR-HepG2)was established.Compared with metformin,the effect of COSG and CS on cell viability and glucose consumption in IR-HepG2 cells was investigated.After cell experiments,the products that had no cytotoxicity and improved glucose consumption were screened out for subsequent animal experiments.Comparing with metformin and insulin,the recovery effect of these products on islet ? cells in T2 DM rats was studied.First of all,COSG and CSGH with different molecular weight and different degree of substitution(DS)were prepared from chitooligosaccharide(COS),chitosan(CS)and dicyandiamide under microwave irradiation.IR and NMR were employed to analyze the structure and molecular weight of the product.Results conformed that the guanidine group was introduced into chitosan main chains.In the second place,the IR HepG2 model was established.COSG and CSGH were used to intervene cells.In terms of overall effectiveness,COSG showed better results than CSGH.Therefore,COSG was selected for subsequent animal experimentsThen,diabetic rat model was established,taking metformin as a reference,the effect of COS and COSG on injury repairmen in islet ? cells of diabetic rats of was observed.The PI3K-Akt,an insulin signaling pathway,and expression level of its downstream signal factor were also researched.The results showed that COS and COSG had good repair effect on islet ? cells in T2 DM rats,and could reduce the blood glucose,urine glucose of diabetic rats,improve insulin secretion in diabetic rats,activate PI3K-Akt signaling pathway.On the one hand,COSG could promote the downstream FoxO1 nuclear output,and then activate PDX-1/GLUT2 / GCK signaling pathway,which is related to insulin secretion.On the other hand,COSG could inhibite GSK-3?/Caspase-3 pathway to prevent apoptosis,and repair cell dysfunction and injury.