目的总结胰高血糖素样肽-1(GLP-1)类似物的研发进展。方法检索PubMed和Web of Science数据库自建库起至2024年2月20日的GLP-1类似物相关文献,从研发概况、单分子多靶点GLP-1受体激动剂(GLP-1RA)、除治疗糖尿病外的其他适应证及其药物研...目的总结胰高血糖素样肽-1(GLP-1)类似物的研发进展。方法检索PubMed和Web of Science数据库自建库起至2024年2月20日的GLP-1类似物相关文献,从研发概况、单分子多靶点GLP-1受体激动剂(GLP-1RA)、除治疗糖尿病外的其他适应证及其药物研发新趋势方面,总结GLP-1类似物的研发进展。结果与结论GLP-1类似物的研发经历了从短效到长效,从注射剂到口服剂,并扩展到多靶点治疗的过程。目前,多靶点GLP-1RA包括GLP-1R/葡萄糖依赖性促胰岛素释放多肽受体、GLP-1R/胰高血糖素受体(GCGR)、GLP-1R/GLP-2R、GLP-1R/胰淀素3受体(AMY3R)、GLP-1R/成纤维细胞生长因子21受体(FGF-21R)等双靶点激动剂,以及GLPR/GLP-1R/GCGR、GLP-1R/GCGR/FGF-21R等三靶点激动剂。GLP-1类似物展现了在2型糖尿病、超重、肥胖症、心血管疾病、多囊卵巢综合征、非酒精性脂肪性肝炎、慢性肾脏病等疾病治疗的巨大潜力,疗效优于单靶点的双靶点和三靶点GLP-1RA是近年来研发的重点。GLP-1类似物的重组腺相关病毒载体基因治疗为研发新趋势,其现阶段存在的安全性、依从性等问题和可供参考的解决方法也一并被提出。展开更多
Objective To explore the molecular mechanism of type 2 diabetes in intrauterine growth restricted adult rats through determination of blood glucose and expression of gluconeogenic enzymes in liver.Methods Male intraut...Objective To explore the molecular mechanism of type 2 diabetes in intrauterine growth restricted adult rats through determination of blood glucose and expression of gluconeogenic enzymes in liver.Methods Male intrauterine growth restriction(IUGR) offspring induced by maternal protein-malnutrition and normal controls were studied.The body weights of offspring rats were weighted from birth to 12 weeks of age.Fasting plasma glucose and insulin levels were determined by glucose oxidase method and enzyme-linked immunosorbent assay(ELISA) respectively at 1 week,8 weeks,and 12 weeks.Peroxisome proliferator-activated receptor-γ coactivator-1α(PGC-1α),phosphoenolpyruvate carboxykinase(PEPCK),and glucose-6-phosphatase(G6Pase) mRNA and protein levels in liver were measured by real time RT-PCR and Western blot in newborn rats(Week 1) and adult rats(Week 12).Results Birth weights of IUGR rats were significantly lower than those of controls until 4 weeks later,when IUGR rats caught up to controls.Between 8 and 12 weeks,the growth of IUGR rats surpassed that of controls.No significant differences were observed in blood glucose and insulin levels at newborn rats between the two groups.However,by the end of 8 weeks IUGR rats developed hyperinsulinemia and high insulin resistance index.At the age of 12 weeks,IUGR rats had mild fasting hyperglycemia.In addition,hepatic PGC-1α mRNA and protein levels as well as hepatic mRNA levels of PEPCK and G6Pase at Week 1 and Week 12 in IUGR rats were all significantly higher than those of controls(P<0.05).Conclusions As a result of intrauterine malnutrition,the expression of gluconeogenic genes is exaggerated in offspring.This change stays through adulthood and may contribute to the pathogenesis of type 2 diabetes.展开更多
To explore the effect of puerarin on insulin receptor （IR）, insulin receptor substrate-1 （IRS-1） and protein expression of protein kinase B （PKB） in the P13K pathway of the glucose consumption, transportation an...To explore the effect of puerarin on insulin receptor （IR）, insulin receptor substrate-1 （IRS-1） and protein expression of protein kinase B （PKB） in the P13K pathway of the glucose consumption, transportation and insulin signal transduction in 3T3-L1 adipoeytes with insulin resistance. The insulin resistance 3T3-L1 adipocytes model was established by free fatty acid induction. The model cells were managed with puerarin in different concentrations. Glucose consumption was detected with glucose oxidase method, glucose transportation rate was determined by 2-deoxy-^3H glucose ingesting method, and the IR, IRS-1 and PKB expression were determined by Western blot. Glucose consumption and transportation were significantly decreased in the model adipoeytes, but increased after treated with puerarin （P 〈 0. 01 ）. Moreover, the level of tyrosine phosphorylation of IR subunit β was higher in the puerarin treated groups, and that of IRS-1 was higher in the group treated with low dose puerarin than that in the model group. The 3T3-L1 adipocytes of insulin resistance model could be induced by free fatty acid successfully, puerarin could promote the glucose utilization in them to alleviate the in- sulin resistance, which may be related with the action in advancing the tyrosine phosphorylation of IR and IRS-1.展开更多
本文介绍2024年5月31日在《美国医学会杂志》发表的论文"Tirzepatide for weight reduction in Chinese adults with obesity:The SURMOUNT-CN randomized clinical trial"的设计、主要结果及其意义。该研究为替尔泊肽治疗肥...本文介绍2024年5月31日在《美国医学会杂志》发表的论文"Tirzepatide for weight reduction in Chinese adults with obesity:The SURMOUNT-CN randomized clinical trial"的设计、主要结果及其意义。该研究为替尔泊肽治疗肥胖的首项中国证据,为肥胖及其合并症的防治提供了强有力的治疗手段。展开更多
文摘目的总结胰高血糖素样肽-1(GLP-1)类似物的研发进展。方法检索PubMed和Web of Science数据库自建库起至2024年2月20日的GLP-1类似物相关文献,从研发概况、单分子多靶点GLP-1受体激动剂(GLP-1RA)、除治疗糖尿病外的其他适应证及其药物研发新趋势方面,总结GLP-1类似物的研发进展。结果与结论GLP-1类似物的研发经历了从短效到长效,从注射剂到口服剂,并扩展到多靶点治疗的过程。目前,多靶点GLP-1RA包括GLP-1R/葡萄糖依赖性促胰岛素释放多肽受体、GLP-1R/胰高血糖素受体(GCGR)、GLP-1R/GLP-2R、GLP-1R/胰淀素3受体(AMY3R)、GLP-1R/成纤维细胞生长因子21受体(FGF-21R)等双靶点激动剂,以及GLPR/GLP-1R/GCGR、GLP-1R/GCGR/FGF-21R等三靶点激动剂。GLP-1类似物展现了在2型糖尿病、超重、肥胖症、心血管疾病、多囊卵巢综合征、非酒精性脂肪性肝炎、慢性肾脏病等疾病治疗的巨大潜力,疗效优于单靶点的双靶点和三靶点GLP-1RA是近年来研发的重点。GLP-1类似物的重组腺相关病毒载体基因治疗为研发新趋势,其现阶段存在的安全性、依从性等问题和可供参考的解决方法也一并被提出。
基金Supported by the National Natural Science Foundation of China(30672237)
文摘Objective To explore the molecular mechanism of type 2 diabetes in intrauterine growth restricted adult rats through determination of blood glucose and expression of gluconeogenic enzymes in liver.Methods Male intrauterine growth restriction(IUGR) offspring induced by maternal protein-malnutrition and normal controls were studied.The body weights of offspring rats were weighted from birth to 12 weeks of age.Fasting plasma glucose and insulin levels were determined by glucose oxidase method and enzyme-linked immunosorbent assay(ELISA) respectively at 1 week,8 weeks,and 12 weeks.Peroxisome proliferator-activated receptor-γ coactivator-1α(PGC-1α),phosphoenolpyruvate carboxykinase(PEPCK),and glucose-6-phosphatase(G6Pase) mRNA and protein levels in liver were measured by real time RT-PCR and Western blot in newborn rats(Week 1) and adult rats(Week 12).Results Birth weights of IUGR rats were significantly lower than those of controls until 4 weeks later,when IUGR rats caught up to controls.Between 8 and 12 weeks,the growth of IUGR rats surpassed that of controls.No significant differences were observed in blood glucose and insulin levels at newborn rats between the two groups.However,by the end of 8 weeks IUGR rats developed hyperinsulinemia and high insulin resistance index.At the age of 12 weeks,IUGR rats had mild fasting hyperglycemia.In addition,hepatic PGC-1α mRNA and protein levels as well as hepatic mRNA levels of PEPCK and G6Pase at Week 1 and Week 12 in IUGR rats were all significantly higher than those of controls(P<0.05).Conclusions As a result of intrauterine malnutrition,the expression of gluconeogenic genes is exaggerated in offspring.This change stays through adulthood and may contribute to the pathogenesis of type 2 diabetes.
基金Sponsored by the Postdoctoral Fund of Heilongjiang Province
文摘To explore the effect of puerarin on insulin receptor （IR）, insulin receptor substrate-1 （IRS-1） and protein expression of protein kinase B （PKB） in the P13K pathway of the glucose consumption, transportation and insulin signal transduction in 3T3-L1 adipoeytes with insulin resistance. The insulin resistance 3T3-L1 adipocytes model was established by free fatty acid induction. The model cells were managed with puerarin in different concentrations. Glucose consumption was detected with glucose oxidase method, glucose transportation rate was determined by 2-deoxy-^3H glucose ingesting method, and the IR, IRS-1 and PKB expression were determined by Western blot. Glucose consumption and transportation were significantly decreased in the model adipoeytes, but increased after treated with puerarin （P 〈 0. 01 ）. Moreover, the level of tyrosine phosphorylation of IR subunit β was higher in the puerarin treated groups, and that of IRS-1 was higher in the group treated with low dose puerarin than that in the model group. The 3T3-L1 adipocytes of insulin resistance model could be induced by free fatty acid successfully, puerarin could promote the glucose utilization in them to alleviate the in- sulin resistance, which may be related with the action in advancing the tyrosine phosphorylation of IR and IRS-1.
文摘本文介绍2024年5月31日在《美国医学会杂志》发表的论文"Tirzepatide for weight reduction in Chinese adults with obesity:The SURMOUNT-CN randomized clinical trial"的设计、主要结果及其意义。该研究为替尔泊肽治疗肥胖的首项中国证据,为肥胖及其合并症的防治提供了强有力的治疗手段。
