Study On The Hypoglycemic Effect And Its Mechanism Of New Sweetener GAMG

Glycyrrhiza has a long history in China as a plant with homology of medicine and food.The main active ingredient of glycyrrhiza is glycyrrhizic acid.Glycyrrhizic acid can produce GAMG after glycyrrhiza removes a monomolecular glucuronic acid,and GAMG is more than 900 times sweeter than sucrose.In this study,the effects and mechanism of long-term exposure of GAMG and other sweeteners GA,stevioside,erythritol,sucralose and aspartame on glucose metabolism in mice were studied,and the function of GAMG in reducing fasting blood glucose and 2h-postprandial blood sugar was further explored.The inhibitory activity and mechanism of GAMG onα-glucosidase were studied.It is of great significance for the market application of GAMG,a novel natural high power sweetener withα-glucosidase inhibitory activity.C57 mice received 20mg/kg body weight GAMG and other sweeteners GA,stevioside,erythritol,sucralose and aspartame for 10 weeks.The results showed that GAMG significantly reduced fasting blood glucose,decreased postprandial blood glucose peak and area under curve,improved glucose tolerance,and increased insulin sensitivity（p<0.05）.Sucralose can increase fasting blood glucose and postprandial blood glucose peak（p<0.05）.All sweeteners had no significant effect on the levels of fasting insulin,serum inflammatory factors and serum lipid.The inhibitory rate of all sweeteners onα-glucosidase showed that only GAMG had a strong inhibitory effect onα-glucosidase at low concentration in a mix-type inhibition manner,with IC₅₀value of 0.733 mg/m L.GAMG quenched the intrinsic fluorescence intensity ofα-glucosidase by forming anα-glucosidase-GAMG complex,and the main forces driving the interaction were hydrogen bonding and hydrophobic interaction in the active sites of the enzyme.GAMG form conventional hydrogen bonds with Arg315 and Glu411,Alkyl interaction with Pro 312 and Tyr 158,and Vander Waals bonds with Ser304and Asp307.Therefore,GAMG is an effectiveα-glucosidase inhibitor that can reduce blood glucose levels.GAMG increased the contents of acetic acid,isobutyric acid and pentanoic acid in colon contents（p<0.05）,butyric acid content in cecum content（p<0.05）and up-regulated the m RNA expression of short-chain fatty acid receptor GPR43（p<0.05）,GAMG tended to promote the secretion of GLP-1（p=0.08）and up-regulate the m RNA expression of PYY（p=0.08）,which increased insulin sensitivity（p<0.05）.Sucralose up-regulated gene expression levels of glucose transporters SGLT-1 and GLUT-2 in intestinal（p<0.05）,thus leading to increased blood glucose.The expression levels of sweet receptor,PPARγand leptin were not significantly affected by all sweeteners.Long-term exposure to sweeteners changed the structure of gut microbiota.LEf Se analysis showed that the GAMG group was rich in three short-chain fatty acid producing bacteria Clostridium＿sensu＿stricto＿1,Ruminiclostridium and Odoribacter,thus increasing short-chain fatty acid content in intestinal contents.Correlation analysis showed that Clostridium＿sensu＿stricto＿1 was negatively correlated with fasting blood glucose levels and positively correlated with short chain fatty acid receptor GPR43 gene expression.In the sucralose group,OTU and Ace index decreased significantly,and the richness of intestinal flora decreased.The key species Adlercreutzia was positively correlated with fasting blood glucose level and insulin resistance index,while negatively correlated with short-chain fatty acid content and insulin sensitivity index.