To evaluate the effect of proteolytic enzymes on the absorption of insulin in the buccal mucosa, the trichloroacetic acid (TCA) method was used to estimate the degradation of insulin under different conditions in the ...To evaluate the effect of proteolytic enzymes on the absorption of insulin in the buccal mucosa, the trichloroacetic acid (TCA) method was used to estimate the degradation of insulin under different conditions in the buccal mucosal homogenates. In vivo experiments estimating the enhancement of hypoglycaemic effect by enzyme inhibitors were also conducted. The results showed that proteolytic enzymes in the buccal mucosa were less active than in the intestine. Bacitracin, aprotinin and sodium deoxycholate could inhibit the degradation of insulin in the buccal mucosal homogenates. The degradation of insulin in buccal mucosal homogenates of normal hamsters was smaller than that of diabetic hamsters. In vivo experiments of hypoglycaemia supported the in vitro results. When given buccally, bacitracin, aprotinin and sodium deoxycholate could increase the relative pharmacological bioavailability of insulin. When co-administered with aprotinin(0.1%), bacitracin(0.5%) and sodium deoxycholate(5%), the relative pharmacological bioavailabilities of insulin were 4.84%, 6.60% and 14.95% respectively. The in vitro and in vivo results suggest that proteolytic enzymes are present in the buccal mucosa, which limit absorption of insulin. Co-administration with some enzyme inhibitors can improve the bioavailability of insulin via buccal delivery and sodium deoxycholte is more efficient than some enzyme inhibitors used for improving buccal absorption.展开更多
Bile acid（BA） is de novo synthesized exclusively in the liver and has direct or indirect antimicrobial effects. On the other hand, the composition and size of the BA pool can be altered by intestinal microbiota via ...Bile acid（BA） is de novo synthesized exclusively in the liver and has direct or indirect antimicrobial effects. On the other hand, the composition and size of the BA pool can be altered by intestinal microbiota via the biotransformation of primary BAs to secondary BAs, and subsequently regulate the nuclear farnesoid X receptor（FXR; NR1H4）. The BA-activated FXR plays important roles in BA synthesis and metabolism, glucose and lipid metabolism, and even hepatic autophagy. BAs can also play a role in the interplays among intestinal microbes. In this review, we mainly discuss the interactions between BAs and intestinal microbiota and their roles in regulating host metabolism, and probably the autophagic signaling pathway.展开更多
Over the past decade,there has been increasing attention on the interaction between microbiota and bile acid metabolism.Bile acids are not only involved in the metabolism of nutrients,but are also important in signal ...Over the past decade,there has been increasing attention on the interaction between microbiota and bile acid metabolism.Bile acids are not only involved in the metabolism of nutrients,but are also important in signal transduction for the regulation of host physiological activities.Microbial-regulated bile acid metabolism has been proven to affect many diseases,but there have not been many studies of disease regulation by microbial receptor signaling pathways.This review considers findings of recent research on the core roles of farnesoid X receptor(FXR),G protein-coupled bile acid receptor(TGR5),and vitamin D receptor(VDR)signaling pathways in microbial–host interactions in health and disease.Studying the relationship between these pathways can help us understand the pathogenesis of human diseases,and lead to new solutions for their treatments.展开更多
Bile acids(BAs)are originally known as detergents essential for the digestion and absorption of lipids.In recent years,extensive research has unveiled new functions of BAs as gut hormones that modulate physiological a...Bile acids(BAs)are originally known as detergents essential for the digestion and absorption of lipids.In recent years,extensive research has unveiled new functions of BAs as gut hormones that modulate physiological and pathological processes,including glucose and lipid metabolism,energy expenditure,inflammation,tumorigenesis,cardiovascular disease,and even the central nervous system in addition to cholesterol homeostasis,enterohepatic protection and liver regeneration.BAs are closely linked with gut microbiota which might explain some of their crucial roles in organs.The signaling actions of BAs can also be mediated through specific nuclear receptors and membranebound G protein-coupled receptors.Several pharmacological agents or bariatric surgeries have demonstrated efficacious therapeutic effects on metabolic diseases through targeting BA signaling.In this mini-review,we summarize recent advances in bile-ology,focusing on its translational studies.展开更多
文摘To evaluate the effect of proteolytic enzymes on the absorption of insulin in the buccal mucosa, the trichloroacetic acid (TCA) method was used to estimate the degradation of insulin under different conditions in the buccal mucosal homogenates. In vivo experiments estimating the enhancement of hypoglycaemic effect by enzyme inhibitors were also conducted. The results showed that proteolytic enzymes in the buccal mucosa were less active than in the intestine. Bacitracin, aprotinin and sodium deoxycholate could inhibit the degradation of insulin in the buccal mucosal homogenates. The degradation of insulin in buccal mucosal homogenates of normal hamsters was smaller than that of diabetic hamsters. In vivo experiments of hypoglycaemia supported the in vitro results. When given buccally, bacitracin, aprotinin and sodium deoxycholate could increase the relative pharmacological bioavailability of insulin. When co-administered with aprotinin(0.1%), bacitracin(0.5%) and sodium deoxycholate(5%), the relative pharmacological bioavailabilities of insulin were 4.84%, 6.60% and 14.95% respectively. The in vitro and in vivo results suggest that proteolytic enzymes are present in the buccal mucosa, which limit absorption of insulin. Co-administration with some enzyme inhibitors can improve the bioavailability of insulin via buccal delivery and sodium deoxycholte is more efficient than some enzyme inhibitors used for improving buccal absorption.
基金Project supported by the National Natural Science Foundation of China(No.31322053)the Hubei Province Distinguished Young Scholar(No.2012FFA015)the Fundamental Research Funds for the Central Universities(Nos.2013PY056 and 2013JQ001),China
文摘Bile acid（BA） is de novo synthesized exclusively in the liver and has direct or indirect antimicrobial effects. On the other hand, the composition and size of the BA pool can be altered by intestinal microbiota via the biotransformation of primary BAs to secondary BAs, and subsequently regulate the nuclear farnesoid X receptor（FXR; NR1H4）. The BA-activated FXR plays important roles in BA synthesis and metabolism, glucose and lipid metabolism, and even hepatic autophagy. BAs can also play a role in the interplays among intestinal microbes. In this review, we mainly discuss the interactions between BAs and intestinal microbiota and their roles in regulating host metabolism, and probably the autophagic signaling pathway.
基金Project supported by the National Key Research and Development Program of China(No.2016YFA0501602)the National Natural Science Foundation of China(Nos.61801108 and 81801478)
文摘Over the past decade,there has been increasing attention on the interaction between microbiota and bile acid metabolism.Bile acids are not only involved in the metabolism of nutrients,but are also important in signal transduction for the regulation of host physiological activities.Microbial-regulated bile acid metabolism has been proven to affect many diseases,but there have not been many studies of disease regulation by microbial receptor signaling pathways.This review considers findings of recent research on the core roles of farnesoid X receptor(FXR),G protein-coupled bile acid receptor(TGR5),and vitamin D receptor(VDR)signaling pathways in microbial–host interactions in health and disease.Studying the relationship between these pathways can help us understand the pathogenesis of human diseases,and lead to new solutions for their treatments.
基金Project supported by the National Cancer Institute(No.2R01CA139158)John Hench Foundation to Wen-dong HUANGthe National Natural Science Foundation of China(Nos.81471084 and 81773793)to Li-hua JIN
文摘Bile acids(BAs)are originally known as detergents essential for the digestion and absorption of lipids.In recent years,extensive research has unveiled new functions of BAs as gut hormones that modulate physiological and pathological processes,including glucose and lipid metabolism,energy expenditure,inflammation,tumorigenesis,cardiovascular disease,and even the central nervous system in addition to cholesterol homeostasis,enterohepatic protection and liver regeneration.BAs are closely linked with gut microbiota which might explain some of their crucial roles in organs.The signaling actions of BAs can also be mediated through specific nuclear receptors and membranebound G protein-coupled receptors.Several pharmacological agents or bariatric surgeries have demonstrated efficacious therapeutic effects on metabolic diseases through targeting BA signaling.In this mini-review,we summarize recent advances in bile-ology,focusing on its translational studies.
