Peptide hormones act through its receptors to regulate a various of physiological processes,including energy metabolism,growth and sleep.The famous helical peptides with important role in maintaining energy metabolic ...Peptide hormones act through its receptors to regulate a various of physiological processes,including energy metabolism,growth and sleep.The famous helical peptides with important role in maintaining energy metabolic balance are glucagon(GCG)and glucagon-like peptide-1(GLP1),which bind to and activate their receptor the Gprotein-coupled receptors(GPCR)GCGR and GLP1R,respectively to regulate blood sugar,food intake and finally body weight.GCG is a gastrointestinal hormone produced in the pancreas,mainly acting opposite to insulin.In response to fasting or acute hypoglycemia,it increases blood glucose by stimulating hepatic gluconeogenesis and glycogen breakdown1.Meanwhile,GCG can affect the energy metabolism and thermogenesis processes of the body2.Studies have shown that exogenous administration of GCG can reduce hepatic triglyceride synthesis and promote hepatic lipolysis3.GLP1 is a hormone primarily produced by intestinal L cells,it binds to its receptor GLP1R expressed mainly on pancreas to enhance insulin secretion in a glucose concentration dependent manner,inhibiting glucagon secretion,and delaying gastric emptying and reduce food intake through central appetite suppression.Thereby,activation of GLP1-GLP1R achieves effects such as lowering blood sugar and weight loss4,5.展开更多
Sennoside A(SA) is a bioactive component of Chinese herbal medicines with an activity of irritant laxative, which is often used in the treatment of constipation and obesity. However, its activity remains unknown in th...Sennoside A(SA) is a bioactive component of Chinese herbal medicines with an activity of irritant laxative, which is often used in the treatment of constipation and obesity. However, its activity remains unknown in the regulation of insulin sensitivity. In this study, the impact of SA on insulin sensitivity was tested in high fat diet(HFD)-induced obese mice through dietary supplementation. At a dosage of 30 mg/kg/day, SA improved insulin sensitivity in the mice after 8-week treatment as indicated by HOMA-IR(homeostatic model assessment for insulin resistance) and glucose tolerance test(GTT). SA restored plasma level of glucagon-like peptide 1(GLP1) by 90% and mRNA expression of Glp1 by 80% in the large intestine of HFD mice. In the mechanism, SA restored the gut microbiota profile, short chain fatty acids(SCFAs), and mucosal structure in the colon. A mitochondrial stress was observed in the enterocytes of HFD mice with ATP elevation, structural damage, and complex dysfunction. The mitochondrial response was induced in enterocytes by the dietary fat as the same responses were induced by palmitic acid in the cell culture. The mitochondrial response was inhibited in HFD mice by SA treatment. These data suggest that SA may restore the function of microbiota–GLP1 axis to improve glucose metabolism in the obese mice.展开更多
文摘Peptide hormones act through its receptors to regulate a various of physiological processes,including energy metabolism,growth and sleep.The famous helical peptides with important role in maintaining energy metabolic balance are glucagon(GCG)and glucagon-like peptide-1(GLP1),which bind to and activate their receptor the Gprotein-coupled receptors(GPCR)GCGR and GLP1R,respectively to regulate blood sugar,food intake and finally body weight.GCG is a gastrointestinal hormone produced in the pancreas,mainly acting opposite to insulin.In response to fasting or acute hypoglycemia,it increases blood glucose by stimulating hepatic gluconeogenesis and glycogen breakdown1.Meanwhile,GCG can affect the energy metabolism and thermogenesis processes of the body2.Studies have shown that exogenous administration of GCG can reduce hepatic triglyceride synthesis and promote hepatic lipolysis3.GLP1 is a hormone primarily produced by intestinal L cells,it binds to its receptor GLP1R expressed mainly on pancreas to enhance insulin secretion in a glucose concentration dependent manner,inhibiting glucagon secretion,and delaying gastric emptying and reduce food intake through central appetite suppression.Thereby,activation of GLP1-GLP1R achieves effects such as lowering blood sugar and weight loss4,5.
基金supported by the National Natural Science Foundation of China(81874377)to Yongning Sunthe National Natural Science Foundation of China(81220108006)to Weiping Jia and Jianping Yesupported by the internal fund of the Shanghai Jiaotong University Affiliated Sixth People’s Hospital East(Shanghai,China)to Jianping Ye and Yongning Sun
文摘Sennoside A(SA) is a bioactive component of Chinese herbal medicines with an activity of irritant laxative, which is often used in the treatment of constipation and obesity. However, its activity remains unknown in the regulation of insulin sensitivity. In this study, the impact of SA on insulin sensitivity was tested in high fat diet(HFD)-induced obese mice through dietary supplementation. At a dosage of 30 mg/kg/day, SA improved insulin sensitivity in the mice after 8-week treatment as indicated by HOMA-IR(homeostatic model assessment for insulin resistance) and glucose tolerance test(GTT). SA restored plasma level of glucagon-like peptide 1(GLP1) by 90% and mRNA expression of Glp1 by 80% in the large intestine of HFD mice. In the mechanism, SA restored the gut microbiota profile, short chain fatty acids(SCFAs), and mucosal structure in the colon. A mitochondrial stress was observed in the enterocytes of HFD mice with ATP elevation, structural damage, and complex dysfunction. The mitochondrial response was induced in enterocytes by the dietary fat as the same responses were induced by palmitic acid in the cell culture. The mitochondrial response was inhibited in HFD mice by SA treatment. These data suggest that SA may restore the function of microbiota–GLP1 axis to improve glucose metabolism in the obese mice.
