Glucagon-Like Peptide-1 and Its Class B G Protein-Coupled Receptors: A Long March to Therapeutic Successes
文献类型：期刊论文
| 作者 | de Graaf, Chris1; Donnelly, Dan2; Wootten, Denise11,12; Lau, Jesper10; Sexton, Patrick M.11,12; Miller, Laurence J.9; Ahn, Jung-Mo8; Liao, Jiayu7; Fletcher, Madeleine M.11,12; Yang, Dehua5,6
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| 刊名 | PHARMACOLOGICAL REVIEWS
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| 出版日期 | 2016-10 |
| 卷号 | 68期号:4页码:954-1013 |
| ISSN号 | 0031-6997 |
| DOI | 10.1124/pr.115.011395 |
| 文献子类 | Review |
| 英文摘要 | The glucagon-like peptide (GLP)-1 receptor (GLP-1R) is a class B G protein-coupled receptor (GPCR) that mediates the action of GLP-1, a peptide hormone secreted from three major tissues in humans, enteroendocrine L cells in the distal intestine, a cells in the pancreas, and the central nervous system, which exerts important actions useful in the management of type 2 diabetes mellitus and obesity, including glucose homeostasis and regulation of gastric motility and food intake. Peptidic analogs of GLP-1 have been successfully developed with enhanced bioavailability and pharmacological activity. Physiologic and biochemical studies with truncated, chimeric, and mutated peptides and GLP-1R variants, together with ligand-bound crystal structures of the extracellular domain and the first three-dimensional structures of the 7-helical transmembrane domain of class B GPCRs, have provided the basis for a two-domain-binding mechanism of GLP-1 with its cognate receptor. Although efforts in discovering therapeutically viable nonpeptidic GLP-1R agonists have been hampered, small-molecule modulators offer complementary chemical tools to peptide analogs to investigate ligand-directed biased cellular signaling of GLP-1R. The integrated pharmacological and structural information of different GLP-1 analogs and homologous receptors give new insights into the molecular determinants of GLP-1R ligand selectivity and functional activity, thereby providing novel opportunities in the design and development of more efficacious agents to treat metabolic disorders. |
| WOS关键词 | PANCREATIC BETA-CELLS ; TYPE-2 DIABETES-MELLITUS ; DEPENDENT INSULINOTROPIC POLYPEPTIDE ; GASTRIC-INHIBITORY POLYPEPTIDE ; TERMINAL EXTRACELLULAR DOMAIN ; SMALL-MOLECULE AGONISTS ; GENE PROMOTER ACTIVITY ; PERFUSED RAT PANCREAS ; EVOLUTIONARILY CONSERVED RESIDUES ; VASOACTIVE-INTESTINAL-PEPTIDE |
| 资助项目 | National Health and Family Planning Commission of China[2012ZX09304-011] ; National Health and Family Planning Commission of China[2013ZX09401003-005] ; National Health and Family Planning Commission of China[2013ZX09507001] ; National Health and Family Planning Commission of China[2013ZX09507-002] ; Chinese Academy of Sciences[00000000] ; Shanghai Science and Technology Development Fund[15DZ2291600] ; Thousand Talents Program in China[00000000] ; National Natural Science Foundation of China[81373463] ; National Health and Medical Research Council of Australia (NHMRC) Principal Research Fellowship[00000000] ; NHMRC[1055134] ; NHMRC[1061044] ; NHMRC[1065410] ; CAS-Novo Nordisk Research Fund[00000000] ; Welch Foundation[AT-1595] ; Juvenile Diabetes Research Foundation[37-2011-20] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000390126100002 |
| 出版者 | AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/275870]  |
| 专题 | 国家新药筛选中心 |
| 通讯作者 | Wang, Ming-Wei |
| 作者单位 | 1.Vrije Univ Amsterdam, Fac Sci, Div Med Chem, Amsterdam, Netherlands; 2.Univ Leeds, Sch Biomed Sci, Leeds, W Yorkshire, England; 3.Fudan Univ, Sch Pharm, Zhangjiang High Tech Pk, Shanghai, Peoples R China 4.Heptares Therapeut, BioPk, Welwyn Garden City, Herts, England; 5.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai, Peoples R China; 6.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, 189 Guo Shou Jing Rd, Shanghai 201203, Peoples R China; 7.Univ Calif Riverside, Dept Bioengn, Bourns Coll Engn, Riverside, CA 92521 USA; 8.Univ Texas Dallas, Dept Chem & Biochem, Richardson, TX 75083 USA; 9.Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Scottsdale, AZ USA; 10.Novo Nordisk AS, Global Res, Prot & Peptide Chem, Malov, Denmark; |
| 推荐引用方式 GB/T 7714 | de Graaf, Chris,Donnelly, Dan,Wootten, Denise,et al. Glucagon-Like Peptide-1 and Its Class B G Protein-Coupled Receptors: A Long March to Therapeutic Successes[J]. PHARMACOLOGICAL REVIEWS,2016,68(4):954-1013. |
| APA | de Graaf, Chris.,Donnelly, Dan.,Wootten, Denise.,Lau, Jesper.,Sexton, Patrick M..,...&Wang, Ming-Wei.(2016).Glucagon-Like Peptide-1 and Its Class B G Protein-Coupled Receptors: A Long March to Therapeutic Successes.PHARMACOLOGICAL REVIEWS,68(4),954-1013. |
| MLA | de Graaf, Chris,et al."Glucagon-Like Peptide-1 and Its Class B G Protein-Coupled Receptors: A Long March to Therapeutic Successes".PHARMACOLOGICAL REVIEWS 68.4(2016):954-1013. |
入库方式： OAI收割
来源：上海药物研究所
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