{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T05:59:11Z","timestamp":1768456751291,"version":"3.49.0"},"reference-count":37,"publisher":"The Endocrine Society","issue":"2","license":[{"start":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T00:00:00Z","timestamp":1766534400000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007028","name":"Leona M. and Harry B. Helmsley Charitable Trust","doi-asserted-by":"publisher","award":["1912-03551"],"award-info":[{"award-number":["1912-03551"]}],"id":[{"id":"10.13039\/100007028","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"publisher","award":["NNF235A0084103"],"award-info":[{"award-number":["NNF235A0084103"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Despite evidence of possible glucagonotropic effects, the role of the gut hormone glucagon-like peptide 2 (GLP-2) in glucose metabolism is unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This work aimed to evaluate the effect of exogenous GLP-2 on plasma glucagon levels during hypoglycemia, euglycemia, and hyperglycemia in healthy male volunteers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A randomized, double-blind, placebo-controlled, crossover study was conducted with supportive ex vivo human islet experiments. Participants included 10 lean, healthy men, median (interquartile range) aged 22 (21-23) years, with body mass index of 23.5 (23.3-23.8) and glycated hemoglobin A1c of 4.8 (4.6-5.1)% (29 (26.5-32.5) mmol\/mol). During 6 separate study days, GLP-2 (6\u2005pmol\/kg\/min for 10\u2005minutes and 2 pmol\/kg\/min for the following 90 minutes) and placebo (saline), respectively, were infused intravenously during insulin-induced hypoglycemia (\u223c2.5\u2005mmol\/L), euglycemia (\u223c5\u2005mmol\/L), or hyperglycemia (\u223c10 mmol\/L). Primary outcome was baseline-subtracted area under the curve for plasma glucagon, and secondary outcomes were serum insulin and C-peptide concentrations. Exploratory outcomes included norepinephrine, growth hormone, and bone homeostatic markers carboxy-terminal collagen crosslinks (CTX) and procollagen type I amino-terminal propeptide (PINP).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>During GLP-2 infusions, steady-state plasma GLP-2 concentrations were 50-fold higher than during placebo. Compared to placebo, GLP-2 increased glucagon secretion slightly during euglycemia, and not during insulin-induced hypoglycemia or hyperglycemia. Ex vivo, GLP-2 did not affect glucagon secretion from isolated human islets. GLP-2 did not affect circulating concentrations of insulin, C-peptide, growth hormone, norepinephrine, or CTX during hypoglycemia, euglycemia, or hyperglycemia. GLP-2 decreased PINP during euglycemia and hyperglycemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Exogenous GLP-2 increased glucagon secretion slightly during euglycemia and not during insulin-induced hypoglycemia or hyperglycemia in healthy young men.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/jendso\/bvaf215","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T12:59:48Z","timestamp":1766149188000},"source":"Crossref","is-referenced-by-count":0,"title":["Glucose-Dependent Effects of Exogenous Glucagon-Like Peptide-2 on Circulating Glucagon Levels in Healthy Men"],"prefix":"10.1210","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0764-8452","authenticated-orcid":false,"given":"Nikolaj E","family":"S\u00f8rum","sequence":"first","affiliation":[{"name":"Center for Clinical Metabolic Research, Gentofte 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,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6853-3805","authenticated-orcid":false,"given":"Jens J","family":"Holst","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen , 2200 Copenhagen N ,","place":["Denmark"]},{"name":"Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen , 2200 Copenhagen N ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8509-2036","authenticated-orcid":false,"given":"Bolette","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen , 2200 Copenhagen N ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8932-5933","authenticated-orcid":false,"given":"Kristine","family":"Henriksen","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Copenhagen , Translational Type 1 Diabetes Research, 2730 Herlev ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7529-4264","authenticated-orcid":false,"given":"Joachim","family":"St\u00f8rling","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen , 2200 Copenhagen N ,","place":["Denmark"]},{"name":"Steno Diabetes Center Copenhagen , Translational Type 1 Diabetes Research, 2730 Herlev ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3525-3772","authenticated-orcid":false,"given":"Jens","family":"Faber","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen , 2200 Copenhagen N ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8774-1797","authenticated-orcid":false,"given":"Mikkel B","family":"Christensen","sequence":"additional","affiliation":[{"name":"Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen , 2900 Hellerup ,","place":["Denmark"]},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen , 2200 Copenhagen N ,","place":["Denmark"]},{"name":"Department of Clinical Pharmacology, Copenhagen University Hospital\u2013Bispebjerg and Frederiksberg , 2400 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