Endothelin-converting enzyme-1 regulates glucagon-like peptide-1 receptor signalling and resensitisation
文献类型：期刊论文
| 作者 | Lu, Jing1,2; Willars, Gary B.2; , |
| 刊名 | BIOCHEMICAL JOURNAL
 |
| 出版日期 | 2019 |
| 卷号 | 476页码:513-533 |
| ISSN号 | 0264-6021 |
| 关键词 | GLP-1 RECEPTOR BETA-ARRESTINS DIFFERENTIAL TRAFFICKING INSULIN-SECRETION SUBSTANCE-P PROTEIN PHOSPHORYLATION GLUCOSE DESENSITIZATION INTERNALIZATION |
| DOI | 10.1042/BCJ20180853 |
| 文献子类 | Article |
| 英文摘要 | Following nutrient ingestion, glucagon-like peptide 1 (GLP-1) is secreted from intestinal L-cells and mediates anti-diabetic effects, most notably stimulating glucose-dependent insulin release from pancreatic beta-cells but also inhibiting glucagon release, promoting satiety and weight reduction and potentially enhancing or preserving beta-cell mass. These effects are mediated by the GLP-1 receptor (GLP-1R), which is a therapeutic target in type 2 diabetes. Although agonism at the GLP-1R has been well studied, desensitisation and resensitisation are perhaps less well explored. An understanding of these events is important, particularly in the design and use of novel receptor ligands. Here, using either HEK293 cells expressing the recombinant human GLP-1R or the pancreatic beta-cell line, INS-1E with endogenous expressesion of the GLP-1R, we demonstrate GLP-1R desensitisation and subsequent resensitisation following removal of extracellular GLP-1 7-36 amide. Resensitisation is dependent on receptor internalisation, endosomal acidification and receptor recycling. Resensitisation is also regulated by endothelin-converting enzyme-1 (ECE-1) activity, most likely through proteolysis of GLP-1 in endosomes and the facilitation of GLP-1R dephosphorylation and recycling. Inhibition of ECE-1 activity also increases GLP-1-induced activation of extracellular signal-regulated kinase and generation of cAMP, suggesting processes dependent upon the lifetime of the internalised ligand-receptor complex. |
| 学科主题 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000462392000006 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/3556]  |
| 专题 | 生化所2019-2020年发文 |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China, 2.Univ Leicester, Dept Mol & Cell Biol, Univ Rd, Leicester LE1 9HN, Leics, England; |
| 推荐引用方式 GB/T 7714 | Lu, Jing,Willars, Gary B.,,. Endothelin-converting enzyme-1 regulates glucagon-like peptide-1 receptor signalling and resensitisation[J]. BIOCHEMICAL JOURNAL,2019,476:513-533. |
| APA | Lu, Jing,Willars, Gary B.,&,.(2019).Endothelin-converting enzyme-1 regulates glucagon-like peptide-1 receptor signalling and resensitisation.BIOCHEMICAL JOURNAL,476,513-533. |
| MLA | Lu, Jing,et al."Endothelin-converting enzyme-1 regulates glucagon-like peptide-1 receptor signalling and resensitisation".BIOCHEMICAL JOURNAL 476(2019):513-533. |
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