典型文献
Signaling profiles in HEK 293T cells co-expressing GLP-1 and GIP receptors
文献摘要：
Glucagon-like peptide-1(GLP-1)and glucose-dependent insulinotropic polypeptide(GIP)are regarded as'incretins'working closely to regulate glucose homeostasis.Unimolecular dual and triple agonists of GLP-1R and GIPR have shown remarkable clinical benefits in treating type 2 diabetes.However,their pharmacological characterization is usually carried out in a single receptor-expressing system.In the present study we constructed a co-expression system of both GLP-1R and GIPR to study the signaling profiles elicited by mono,dual and triple agonists.We show that when the two receptors were co-expressed in HEK 293T cells with comparable receptor ratio to pancreatic cancer cells,GIP predominately induced cAMP accumulation while GLP-1 was biased towards β-arrrestin 2 recruitment.The presence of GIPR negatively impacted GLP-1 R-mediated cAMP and β-arrestin 2 responses.While sharing some common modulating features,dual agonists(peptide 19 and LY3298176)and a triple agonist displayed differentiated signaling profiles as well as negative impact on the heteromerization that may help interpret their superior clinical efficacies.
文献关键词：
中图分类号：
作者姓名：
Yu-zhe Wang;De-hua Yang;Ming-wei Wang
作者机构：
The National Center for Drug Screening,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China;University of Chinese Academy of Sciences,Beijing 100049,China;The CAS Key Laboratory of Receptor Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China;Department of Pharmacology,School of Basic Medical Sciences,Fudan University,Shanghai 200032,China
文献出处：
引用格式：
[1]Yu-zhe Wang;De-hua Yang;Ming-wei Wang-.Signaling profiles in HEK 293T cells co-expressing GLP-1 and GIP receptors)[J].中国药理学报（英文版）,2022(06):1453-1460
A类：
incretins,Unimolecular,GIPR,arrrestin,LY3298176,heteromerization
B类：
Signaling,profiles,HEK,293T,cells,expressing,GLP,receptors,Glucagon,like,glucose,dependent,insulinotropic,polypeptide,are,regarded,working,closely,regulate,homeostasis,dual,triple,agonists,1R,have,shown,remarkable,clinical,benefits,treating,type,diabetes,However,their,pharmacological,characterization,usually,carried,out,single,system,In,present,study,constructed,expression,both,signaling,elicited,by,mono,We,that,when,two,were,expressed,comparable,ratio,pancreatic,cancer,predominately,induced,cAMP,accumulation,while,was,biased,towards,recruitment,presence,negatively,impacted,mediated,arrestin,responses,While,sharing,some,common,modulating,features,displayed,differentiated,well,may,help,interpret,superior,efficacies
AB值：
0.552429
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