Pharmacological characterization of mono-, dual- and tri-peptidic agonists at GIP and GLP-1 receptors
文献类型：期刊论文
| 作者 | Yuliantie, Elita2,3,4; Darbalaei, Sanaz2,3,4; Dai, Antao2,3; Zhao, Peishen5; Yang, Dehua2,3 ; Sexton, Patrick M.5; Wang, Ming-Wei1,2,3,4; Wootten, Denise5
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| 刊名 | BIOCHEMICAL PHARMACOLOGY
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| 出版日期 | 2020-07-01 |
| 卷号 | 177页码:13 |
| 关键词 | G protein-coupled receptor Glucose-dependent insulinotropic peptide receptor Glucagon-like peptide-1 receptor Biased agonist GPCR signaling |
| ISSN号 | 0006-2952 |
| DOI | 10.1016/j.bcp.2020.114001 |
| 通讯作者 | Sexton, Patrick M.(patrick.sexton@monash.edu) ; Wang, Ming-Wei(mwwang@simm.ac.cn) ; Wootten, Denise(denise.wootten@monash.edu) |
| 英文摘要 | Glucose-dependent insulinotropic peptide (GIP) is an incretin hormone with physiological roles in adipose tissue, the central nervous system and bone metabolism. While selective ligands for GIP receptor (GIPR) have not been advanced for disease treatment, dual and triple agonists of GIPR, in conjunction with that of glucagon-like peptide-1 (GLP-1) and glucagon receptors, are currently in clinical trials, with an expectation of enhanced efficacy beyond that of GLP-1 receptor (GLP-1R) agonist monotherapy for diabetic patients. Consequently, it is important to understand the pharmacological behavior of such drugs. In this study, we have explored signaling pathway specificity and the potential for biased agonism of mono-, dual- and tri-agonists of GIPR using human embryonic kidney 293 (HEK293) cells recombinantly expressing human GIPR or GLP-1R. Compared to GIP (1-42), the GIPR mono-agonists Pro3GIP and Lys3GIP are biased towards ERK1/2 phosphorylation (pERK1/2) relative to cAMP accumulation at GIPR, whereas the triple agonist at GLP-1R/GCGR/GIPR is biased towards pERK1/2 relative to beta-arrestin2 recruitment. Moreover, the dual GIPR/GLP-1R agonist, LY3298176, is biased towards pERK1/2 relative to cAMP accumulation at both GIPR and GLP-1R compared to their respective endogenous ligands. These data reveal novel pharmacological properties of potential therapeutic agents that may impact on diversity in clinical responses. |
| WOS关键词 | DEPENDENT INSULINOTROPIC POLYPEPTIDE ; GLUCAGON-LIKE PEPTIDE-1 ; ANTAGONIST ; SECRETION ; OBESITY ; BIAS ; ABNORMALITIES ; BINDING ; RAT |
| 资助项目 | National Natural Science Foundation of China[81872915] ; National Natural Science Foundation of China[81973373] ; National Natural Science Foundation of China[81773792] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09735-001] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09711002-002-005] ; National Key R&D Program of China[2018YFA0507000] ; Novo Nordisk-CAS Research Fund[NNCAS-2017-1-CC] ; National Health and Medical Research Council of Australia (NHMRC)[1184726] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000541248000063 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/291860]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Sexton, Patrick M.; Wang, Ming-Wei; Wootten, Denise |
| 作者单位 | 1.Fudan Univ, Shanghai Med Coll, Shanghai 200032, Peoples R China 2.Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, CAS Key Lab Receptor Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 5.Monash Univ, Monash Inst Pharmaceut Sci, Drug Discovery Biol Theme, Parkville, Vic 3052, Australia |
| 推荐引用方式 GB/T 7714 | Yuliantie, Elita,Darbalaei, Sanaz,Dai, Antao,et al. Pharmacological characterization of mono-, dual- and tri-peptidic agonists at GIP and GLP-1 receptors[J]. BIOCHEMICAL PHARMACOLOGY,2020,177:13. |
| APA | Yuliantie, Elita.,Darbalaei, Sanaz.,Dai, Antao.,Zhao, Peishen.,Yang, Dehua.,...&Wootten, Denise.(2020).Pharmacological characterization of mono-, dual- and tri-peptidic agonists at GIP and GLP-1 receptors.BIOCHEMICAL PHARMACOLOGY,177,13. |
| MLA | Yuliantie, Elita,et al."Pharmacological characterization of mono-, dual- and tri-peptidic agonists at GIP and GLP-1 receptors".BIOCHEMICAL PHARMACOLOGY 177(2020):13. |
入库方式： OAI收割
来源：上海药物研究所
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