{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:02:55Z","timestamp":1790751775184,"version":"4.1.0"},"reference-count":79,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004070","name":"Khalifa University of Science, Technology and Research","doi-asserted-by":"publisher","award":["FSU\u20102023\u201018"],"award-info":[{"award-number":["FSU\u20102023\u201018"]}],"id":[{"id":"10.13039\/501100004070","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004070","name":"Khalifa University of Science, Technology and Research","doi-asserted-by":"publisher","award":["RIG\u20102024\u2010004"],"award-info":[{"award-number":["RIG\u20102024\u2010004"]}],"id":[{"id":"10.13039\/501100004070","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004070","name":"Khalifa University of Science, Technology and Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004070","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006013","name":"United Arab Emirates University","doi-asserted-by":"publisher","award":["Start\u2010Up 12S244"],"award-info":[{"award-number":["Start\u2010Up 12S244"]}],"id":[{"id":"10.13039\/501100006013","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Haemorphins are known to target G protein\u2010coupled receptors and their reduced serum levels were associated with diabetes and obesity. This is consistent with inhibitory action on dipeptidyl peptidase IV, controlling GLP\u20101 levels. The modulation of the GLP\u20101 receptor by haemorphins as a mechanism for regulating glucose homeostasis was investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>The effect of LVV\u2010haemorphin 7 (LVV\u2010H7) on GLP\u20101 receptor was assessed in human embryonic kidney (HEK293) and rat insulinoma (INS\u20101 832\/3) cells using bioluminescence resonance energy transfer, downstream signalling, cell viability, insulin synthesis experimental and computational ligand binding analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      LVV\u2010H7 has positive action on GLP\u20101 receptor occurring with GLP\u20101 but not orforglipron (LY3502970), indicating a peptide\u2013peptide interaction, causing a left shift in GLP\u20101's dose responses. LVV\u2010H7 also potentiated GLP\u20101\u2010induced insulin expression and its protective effect against glucose\u2010induced cytotoxicity. Moreover, LVV\u2010H7 slightly reduced the GLP\u20101's association kinetics with no impact on its binding properties. Molecular docking supported by functional analysis showed the existence of a putative \u2018allosteric\u2019 binding site at the junction between the helical and the extracellular domains (ECDs) and highlighted the critical role of Trp6 of LVV\u2010H7 and Ser31\n                      <jats:sup>ECD<\/jats:sup>\n                      \/Glu34\n                      <jats:sup>ECD<\/jats:sup>\n                      \/Arg299\n                      <jats:sup>ECL2<\/jats:sup>\n                      \/Asp372\n                      <jats:sup>ECL3<\/jats:sup>\n                      \/Arg380\n                      <jats:sup>ECL3\/<\/jats:sup>\n                      \u2122\n                      <jats:sup>7<\/jats:sup>\n                      of GLP\u20101 receptor. This also demonstrated that active GLP\u20101\/GLP\u20101 receptor complex is required for the positive action of LVV\u2010H7.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>LVV\u2010H7 is active on the GLP\u20101 receptor\u2010mediated metabolic pathways in pancreatic \u03b2\u2010cells. This is consistent with reduced serum haemorphin levels in diabetes\/obesity, suggesting implications in glucose homeostasis. This constitutes the first Class B GPCR modulated by haemorphins, illustrating the role of haemorphin\u2010GPCR axis in physiology\/pathophysiology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70677","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:40:02Z","timestamp":1790750402000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Positive modulation of glucagon\u2010like peptide 1 (GLP\u20101) receptor by endogenous haemorphins with implications in glucose metabolism and diabetes"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9030-4152","authenticated-orcid":false,"given":"Farheen Badrealam","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, College of Medicine and Health Sciences Khalifa University  Abu Dhabi The United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9880-8991","authenticated-orcid":false,"given":"Rwdah Mohamed","family":"Alameri","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Medicine and Health Sciences Khalifa University  Abu Dhabi The United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasir S.","family":"Raouf","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science The United Arab Emirates University  Al Ain The United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1281-0871","authenticated-orcid":false,"given":"Damien","family":"Maurel","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9nomique Fonctionnelle Universit\u00e9 de Montpellier, CNRS, INSERM  Montpellier Cedex 5 France"},{"name":"ARPEGE Pharmacology Screening Interactome Platform Facility, Institut de G\u00e9nomique Fonctionnelle Universit\u00e9 de Montpellier, CNRS, INSERM  Montpellier Cedex 05 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1150-1794","authenticated-orcid":false,"given":"Naiem Ahmad","family":"Wani","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Engineering and Physical Sciences Khalifa University  Abu Dhabi The United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7198-7920","authenticated-orcid":false,"given":"Anatoliy","family":"Shmygol","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine and Health Sciences The United Arab Emirates University  Al Ain The United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3034-6881","authenticated-orcid":false,"given":"Irfa","family":"Anwar","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science The United Arab Emirates University  Al Ain The United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng B.","family":"See","sequence":"additional","affiliation":[{"name":"Molecular Endocrinology and Pharmacology, Harry Perkins Institute of Medical Research and Centre for Medical Research The University of Western Australia  Nedlands Western Australia Australia"},{"name":"Australian Research Council Centre for Personalised Therapeutics Technologies  Perth Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7990-371X","authenticated-orcid":false,"given":"Elizabeth K. M.","family":"Johnstone","sequence":"additional","affiliation":[{"name":"Molecular Endocrinology and Pharmacology, Harry Perkins Institute of Medical Research and Centre for Medical Research The University of Western Australia  Nedlands Western Australia Australia"},{"name":"Australian Research Council Centre for Personalised Therapeutics Technologies  Perth Western Australia Australia"},{"name":"School of Biomedical Science, Pharmacology and Toxicology The University of Western Australia  Nedlands Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8113-0957","authenticated-orcid":false,"given":"Elodie","family":"Dupuis","sequence":"additional","affiliation":[{"name":"Life Sciences Reagents Cisbio Bioassays, a company affiliated with Revvity Health Sciences Inc.  Codolet France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1205-686X","authenticated-orcid":false,"given":"Eric","family":"Trinquet","sequence":"additional","affiliation":[{"name":"Life Sciences Reagents Cisbio Bioassays, a company affiliated with Revvity Health Sciences Inc.  Codolet France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8261-9189","authenticated-orcid":false,"given":"Kevin D. G.","family":"Pfleger","sequence":"additional","affiliation":[{"name":"Molecular Endocrinology and Pharmacology, Harry Perkins Institute of Medical Research and Centre for Medical Research The University of Western Australia  Nedlands Western Australia Australia"},{"name":"Australian Research Council Centre for Personalised Therapeutics Technologies  Perth Western Australia Australia"},{"name":"Dimerix Limited  Fitzroy Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0228-6394","authenticated-orcid":false,"given":"Emilia","family":"Oueis","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Engineering and Physical Sciences Khalifa University  Abu Dhabi The United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0022-578X","authenticated-orcid":false,"given":"Mohammed Akli","family":"Ayoub","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Medicine and Health Sciences Khalifa University  Abu Dhabi The United Arab Emirates"},{"name":"Food Security and Technology Center Khalifa University of Science and Technology  Abu Dhabi United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.70230"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.70234"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.70233"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.70229"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22010209"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.01258"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.2253"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25053059"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph14030225"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.382481"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2012.08.003"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-020-0589-7"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adp7040"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2012.03.019"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cccn.2003.07.011"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28789-5"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.17441"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-022-00962-y"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.109.198309"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20150253"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adn4128"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2008.11.004"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2010.02.019"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm0306430"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm051256o"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.8.2480"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2013.427"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-023-00889-6"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)31150-X"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2021.101040"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci800324m"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm030644s"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c01589"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32261-X"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6446(05)03370-2"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1612917"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature22800"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-45680-7"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03941-2"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2017.08.011"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2014879117"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-010-2028-x"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12735"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-023-01734-8"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705177"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.2431"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(89)90368-3"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI92172"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/oby.20280"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1603827"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41366-024-01473-y"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26133879"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4MD00383G"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28248107"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2023.175896"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2024.116552"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.02.139"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-09808-8"},{"key":"e_1_2_12_61_1","first-page":"22","article-title":"LVV\u2010hemorphin\u20103 affects secretion and plasma concentrations of insulin and glucagon in streptozotocin\u2010induced diabetic rats","volume":"55","author":"Sarukhanyan F.","year":"2015","journal-title":"Medical Science of Armenia"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.26450"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0710402105"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2023.09.029"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-16590-0"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.4397"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28020751"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-010919-023301"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.05.023"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16158"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00239-025-10237-9"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2006.10.001"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2024.116632"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.09.020"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2021.04.008"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature22394"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbcM116.726620"},{"key":"e_1_2_12_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01931-z"},{"key":"e_1_2_12_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2025.03.003"},{"key":"e_1_2_12_80_1","doi-asserted-by":"publisher","DOI":"10.1177\/1087057110384611"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.70677","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bph.70677","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.70677","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:40:04Z","timestamp":1790750404000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.70677"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,29]]},"references-count":79,"alternative-id":["10.1111\/bph.70677"],"URL":"https:\/\/doi.org\/10.1111\/bph.70677","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,29]]},"assertion":[{"value":"2025-09-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"bph.70677"}}