{"doi":"10.1007/s00125-023-05947-y","title":"100 years of glucagon and 100 more","abstract":null,"journal":"Diabetologia","year":2023,"id":619520,"datarank":0.7050720548688626,"base_score":4.700480365792417,"endowment":4.700480365792417,"self_citation_contribution":0.7050720548688626,"citation_network_contribution":0.0,"self_endowment_contribution":0.7050720548688626,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":109,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":226898,"name":"Jens J. Holst","orcid":"0000-0001-6853-3805","position":1,"is_corresponding":false},{"id":120537,"name":"Alan D. Cherrington","orcid":null,"position":2,"is_corresponding":false},{"id":63184,"name":"Brian Finan","orcid":"0000-0002-6467-0447","position":3,"is_corresponding":false},{"id":18199,"name":"Lise Lotte Gluud","orcid":"0000-0002-9462-4468","position":4,"is_corresponding":false},{"id":343974,"name":"E. Danielle Dean","orcid":"0000-0002-7157-5683","position":5,"is_corresponding":false},{"id":986780,"name":"Jonathan E. Campbell","orcid":"0000-0001-8223-1600","position":6,"is_corresponding":false},{"id":772928,"name":"Stephen R. Bloom","orcid":"0000-0003-1542-2348","position":7,"is_corresponding":false},{"id":1598798,"name":"Tricia M.-M. Tan","orcid":null,"position":8,"is_corresponding":false},{"id":197426,"name":"Filip K. Knop","orcid":"0000-0002-2495-5034","position":9,"is_corresponding":false},{"id":63189,"name":"Timo D. Müller","orcid":"0000-0002-0624-9339","position":10,"is_corresponding":false},{"id":277538,"name":"Nicolai J. Wewer Albrechtsen","orcid":"0000-0003-4230-5753","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"100 years of glucagon and 100 more","abstract":"The peptide hormone glucagon, discovered in late 1922, is secreted from pancreatic alpha cells and is an essential regulator of metabolic homeostasis. This review summarises experiences since the discovery of glucagon regarding basic and clinical aspects of this hormone and speculations on the future directions for glucagon biology and glucagon-based therapies. The review was based on the international glucagon conference, entitled 'A hundred years with glucagon and a hundred more', held in Copenhagen, Denmark, in November 2022. The scientific and therapeutic focus of glucagon biology has mainly been related to its role in diabetes. In type 1 diabetes, the glucose-raising properties of glucagon have been leveraged to therapeutically restore hypoglycaemia. The hyperglucagonaemia evident in type 2 diabetes has been proposed to contribute to hyperglycaemia, raising questions regarding underlying mechanism and the importance of this in the pathogenesis of diabetes. Mimicry experiments of glucagon signalling have fuelled the development of several pharmacological compounds including glucagon receptor (GCGR) antagonists, GCGR agonists and, more recently, dual and triple receptor agonists combining glucagon and incretin hormone receptor agonism. From these studies and from earlier observations in extreme cases of either glucagon deficiency or excess secretion, the physiological role of glucagon has expanded to also involve hepatic protein and lipid metabolism. The interplay between the pancreas and the liver, known as the liver-alpha cell axis, reflects the importance of glucagon for glucose, amino acid and lipid metabolism. In individuals with diabetes and fatty liver diseases, glucagon's hepatic actions may be partly impaired resulting in elevated levels of glucagonotropic amino acids, dyslipidaemia and hyperglucagonaemia, reflecting a new, so far largely unexplored pathophysiological phenomenon termed 'glucagon resistance'. Importantly, the hyperglucagonaemia as part of glucagon resistance may result in increased hepatic glucose production and hyperglycaemia. Emerging glucagon-based therapies show a beneficial impact on weight loss and fatty liver diseases and this has sparked a renewed interest in glucagon biology to enable further pharmacological pursuits.","is_dataset_classified":null,"base_score":4.700480365792417,"endowment":4.700480365792417,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"37367959","pmcid":"PMC13288116","openalex_id":"https://openalex.org/W4382182595","authors":[],"funders":[{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"GRK 2816/1","title":null},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"SFB1123","title":null},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"TRR152","title":null},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"TRR296","title":null},{"funder_name":"Novo Nordisk Fonden","grant_id":"NNF21OC0072718","title":null},{"funder_name":"European Foundation for the Study of Diabetes","grant_id":"NNF21SA0072746","title":null},{"funder_name":"H2020 European Research Council","grant_id":"101044445","title":"CenTral and PeRipheral NervoUs SyStem acTion of GIPR in ObEsity and Diabetes"},{"funder_name":"Danmarks Frie Forskningsfond","grant_id":"1052-00003B","title":null},{"funder_name":"National Institute for Health and Care Research","grant_id":"R01DK132669","title":null},{"funder_name":"NNF Center for Basic Metabolic Research","grant_id":"Holst Group","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"P30 DK020593","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK123075","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK141090","title":null},{"funder_name":"Steno Diabetes Center Copenhagen (SDCC)","grant_id":"SDCC 3.F CMP","title":null},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"unidentified","title":"unidentified"},{"funder_name":"National Institutes of Health","grant_id":"5R01DK132669-04","title":"Arginine regulation of alpha cell proliferation and function"},{"funder_name":"National Institutes of Health","grant_id":"1R01DK117147-01A1","title":"Molecular Mechanisms of Postnatal Islet alpha-cell Proliferation"},{"funder_name":"Deutsche Diabetes Gesellschaft","grant_id":"","title":null}],"total_grants":18,"fwci":16.3517,"citation_percentile":0.99424048,"influential_citations":0,"citation_trend":[{"year":2023,"count":9},{"year":2024,"count":37},{"year":2025,"count":39},{"year":2026,"count":24}],"oa_status":"bronze","license":"Springer Nature TDM","oa_locations":[{"url":"https://link.springer.com/content/pdf/10.1007/s00125-023-05947-y.pdf","host_type":"journal"},{"url":"https://link.springer.com/content/pdf/10.1007/s00125-023-05947-y.pdf","host_type":"publisher"},{"url":"https://link.springer.com/article/10.1007/s00125-023-05947-y/fulltext.html","host_type":"publisher"},{"url":"https://doi.org/10.1007/s00125-023-05947-y","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/37367959","host_type":"repository"},{"url":"https://researchprofiles.ku.dk/da/publications/de2b3edb-61e7-4f18-8b58-fe154ef1a00c","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13288116/","host_type":"repository"},{"url":"https://push-zb.helmholtz-munich.de/frontdoor.php?source_opus=68468","host_type":"repository"},{"url":"https://curis.ku.dk/ws/files/374892980/s00125_023_05947_y.pdf","host_type":"repository"},{"url":"http://dx.doi.org/10.1007/s00125-023-05947-y","host_type":""},{"url":"https://doi.org/https://doi.org/10.1007/s00125-023-05947-y","host_type":""}],"fields_of_study":["Diabetes Treatment and Management","Diet and metabolism studies","Pancreatic function and diabetes","0303 health sciences","03 medical and health sciences"],"mesh_terms":["Amino Acids","Diabetes Mellitus, Type 2","Glucagon","Glucose","Humans","Hyperglycemia","Non-alcoholic Fatty Liver Disease"],"keywords":["Human physiology","Glucagon","Medicine","Internal medicine","Insulin","Amino acids","Review","Diabetes","gluconeogenesis","Nafld","Glucagon Receptor","Gcgr","Co-agonists","Glucose","Diabetes Mellitus, Type 2","Amino Acids ; Co-agonists ; Diabetes ; Gcgr ; Glucagon ; Glucagon Receptor ; Gluconeogenesis ; Nafld ; Review","Non-alcoholic Fatty Liver Disease","Hyperglycemia","Humans"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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