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We investigated the dose\u2010dependent effects of glucagon on glucose metabolism, \u03b2\u2010cell secretion and markers of hepatic metabolism in healthy adults.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      Fifteen healthy, lean adults underwent a 180\u2010min stepwise intravenous infusion of native human glucagon at six increasing doses (0.01, 0.1, 0.5, 1, 10 and 50\u2009ng\u2009\u00d7\u2009kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      \u2009\u00d7\u2009min\n                      <jats:sup>\u22121<\/jats:sup>\n                      ). Plasma glucose, insulin, C\u2010peptide, cyclic AMP (cAMP), non\u2010esterified fatty acids, triglycerides, total amino acids and urea were measured repeatedly throughout the study.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Plasma glucose increased in a dose\u2010dependent manner, with significant stepwise elevations observed from intermediate infusion rates and reaching peak levels at supraphysiological glucagon levels. Insulin and C\u2010peptide levels rose markedly, reflecting \u03b2\u2010cell activation. Plasma cAMP increased only during the highest glucagon infusion rate, despite earlier metabolic responses. Plasma non\u2010esterified fatty acids, triglycerides and total amino acids declined at higher glucagon doses, whilst plasma urea decreased gradually from the second infusion rate onward.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Infusion of glucagon results in dose\u2010dependent metabolic effects in healthy humans. The differential timing of glucose, lipid and amino acid responses relative to systemic cAMP elevations could be consistent with pathway\u2010specific activation thresholds rather than uniform signalling. These findings provide new insights into human glucagon physiology with potential relevance for metabolic diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70896","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T04:56:45Z","timestamp":1779425805000},"page":"6941-6949","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dose\u2013Response Effect of Glucagon on Glucose, Beta\u2010Cell Secretion and Metabolism in Healthy Individuals"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-7258-3017","authenticated-orcid":false,"given":"Sophie Betty","family":"Brock","sequence":"first","affiliation":[{"name":"Department of Clinical Biochemistry Copenhagen University Hospital Bispebjerg and Frederiksberg  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6528-5615","authenticated-orcid":false,"given":"Nina Lerberg","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry Copenhagen University Hospital Bispebjerg and Frederiksberg  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6031-1857","authenticated-orcid":false,"given":"Elvar M\u00e1r","family":"Sturlaugsson J\u00f3h\u00f6nnuson","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry Copenhagen University Hospital Bispebjerg and Frederiksberg  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasha Alexandra Sampson","family":"Kjeldsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry Copenhagen University Hospital Bispebjerg and Frederiksberg  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4230-5753","authenticated-orcid":false,"given":"Nicolai J.","family":"Wewer Albrechtsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry Copenhagen University Hospital Bispebjerg and Frederiksberg  Copenhagen Denmark"},{"name":"Copenhagen Center for Translational Research Copenhagen University Hospital Bispebjerg and Frederiksberg  Copenhagen Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen 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