ABSTRACT
AIM To explore the antihyperglycemic mechanism of Polygonatum odoratum polysaccharides based on sweet taste receptor signaling pathway.METHODS After the successful diabetic modeling by high-fat and high-sugar diet combined with streptozotocin,the rats were randomly divided into the model group,the metformin group(200 mg/kg)and the low,medium and high dose P.odoratum polysaccharides groups(100,200 and 400 mg/kg),in contrast to the control group with 8 normal rats.The rats had measurement of their fasting blood glucose level from tail vein blood before the intervention and 2,4,6 and 8 weeks after the corresponding administration;detection of their serum GLP-1 and insulin levels by ELISA,and their oral glucose tolerance test after 7 weeks;detection of their blood lipid level,observation of their morphology of pancreas and liver,and detection of their mRNA expressions of T1R2,T1R3,α-gustducin,TRPM5,SGLT-1 and GLUT-2 in ileum by RT-qPCR after 8 weeks.HuTu-80 cells treated with P.odoratum polysaccharides solution had their the levels of cAMP and GLP-1 detected by ELISA;their fluorescence intensity of Ca2+ detected by laser confocal method;and the expression of sweet taste receptor mRNA detected by RT-qPCR.RESULTS The result of animal experiments showed that the groups intervened with middle or high dose of P.odoratum polysaccharides displayed decreased levels of fasting blood glucose,area under the time-blood glucose curve(AUC)and the levels of serum TG,TC and LDL-C(P<0.05),increased levels of serum GLP-1 and insulin and the mRNA expressions of T1R2 and TRPM5 in ileum(P<0.05),in contrast to the model group,in addition to the increased serum HDL-C level and mRNA expressions of T1R2,α-gustducin in ileum tissue in the high dose group.The result of cell experiment showed that P.odoratum polysaccharides increased the levels of cAMP,GLP-1 and Ca2+ in cells(P<0.05),and enhanced the mRNA expressions of sweet taste receptors T1R2 and T1R3(P<0.05).CONCLUSION P.odoratum polysaccharides may contribute antihyperglycemic effects through GLP-1 secretion promotion via activation of the sweet taste receptor signaling pathway due to its efficacy in up-regulating expression of molecules.