{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T21:32:39Z","timestamp":1783632759584,"version":"3.55.0"},"reference-count":45,"publisher":"The Endocrine Society","issue":"3","license":[{"start":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T00:00:00Z","timestamp":1724284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012774","name":"Innovation Fund Denmark","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012774","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Antag Therapeutics Aps"},{"DOI":"10.13039\/501100004954","name":"Augustinus Fonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004954","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008269","name":"L\u00e6ge Sofus Carl Emil Friis og hustru Olga Doris Friis\u2019 Legat","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>About 30% of patients with active acromegaly experience paradoxically increased growth hormone (GH) secretion during the diagnostic oral glucose tolerance test (OGTT). Endogenous glucose-dependent insulinotropic polypeptide (GIP) is implicated in this paradoxical secretion.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>We used the GIP receptor (GIPR) antagonist GIP(3-30)NH2 to test the hypothesis that GIP mediates this paradoxical response when GIPR is abundantly expressed in somatotropinomas.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A total of 25 treatment-naive patients with acromegaly were enrolled. Each patient underwent one OGTT during simultaneous placebo infusion and one OGTT during a GIP(3-30)NH2 infusion. Blood samples were drawn at baseline and regularly after infusions to measure GH. We assessed pituitary adenoma size by magnetic resonance imaging and GIPR expression by immunohistochemistry on resected somatotropinomas. For mechanistic confirmation, we applied in vitro and ex vivo approaches. The main outcome measure was the effect of GIP(3-30)NH2 on paradoxical GH secretion during OGTT as a measure of GIP involvement.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In 4 of 7 patients with paradoxical GH secretion, GIP(3-30)NH2 infusion completely abolished the paradoxical response (P = .0003). Somatotrophs were available from 3 of 4 of these patients, all showing abundant GIPR expression. Adenoma size did not differ between patients with and without paradoxical GH secretion.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Of 25 patients with acromegaly, 7 had paradoxical GH secretion during OGTT, and pharmaceutical GIPR blockade abolished this secretion in 4. Corresponding somatotroph adenomas abundantly expressed GIPR, suggesting a therapeutic target in this subpopulation of patients. In vitro and ex vivo analyses confirmed the role of GIP and the effects of the antagonist.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgae583","type":"journal-article","created":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T23:28:36Z","timestamp":1724369316000},"page":"715-729","source":"Crossref","is-referenced-by-count":12,"title":["GIP Receptor Antagonism Eliminates Paradoxical Growth Hormone Secretion in Some Patients With Acromegaly"],"prefix":"10.1210","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8591-9814","authenticated-orcid":false,"given":"Mette H","family":"Jensen","sequence":"first","affiliation":[{"name":"Antag Therapeutics Aps , 2200 Copenhagen ,","place":["Denmark"]},{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen , 2200 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7880-8515","authenticated-orcid":false,"given":"L\u00e6rke S","family":"Gasbjerg","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen , 2200 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsa","family":"Skov-Jeppesen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen , 2200 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens C B","family":"Jacobsen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen , 2200 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steen S","family":"Poulsen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen , 2200 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuiqi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Pituitary Center, Department of Medicine, Cedars-Sinai Medical Center , Los Angeles, CA 90048 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruta","family":"Jakubauskaite","sequence":"additional","affiliation":[{"name":"Department of Radiology, Copenhagen University Hospital Rigshospitalet , 2100 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frantz R","family":"Poulsen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Odense University Hospital , 5000 Odense ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Bonde","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Odense University Hospital , 5000 Odense ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud","family":"Albarazi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Internal Medicine, Aarhus University Hospital , 8200 Aarhus ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Halle","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Odense University Hospital , 5000 Odense ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte B","family":"Christiansen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen , 2200 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samra J","family":"Sanni","sequence":"additional","affiliation":[{"name":"Antag Therapeutics Aps , 2200 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Byberg","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen , 2200 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1625-3558","authenticated-orcid":false,"given":"Bj\u00f8rn","family":"Hoe","sequence":"additional","affiliation":[{"name":"Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen , 2900 Hellerup ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens J","family":"Holst","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen , 2200 Copenhagen ,","place":["Denmark"]},{"name":"Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen , 2200 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9970-9535","authenticated-orcid":false,"given":"Flemming","family":"Dela","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen , 2200 Copenhagen ,","place":["Denmark"]},{"name":"Department of Human Physiology and Biochemistry, Riga Stradi\u0146\u0161 University , Riga LV-1007 ,","place":["Latvia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aase K","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Copenhagen University Hospital Rigshospitalet , 2100 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filip K","family":"Knop","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 ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai C","family":"Arlien-S\u00f8borg","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Internal Medicine, Aarhus University Hospital , 8200 Aarhus ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2355-3447","authenticated-orcid":false,"given":"Shlomo","family":"Melmed","sequence":"additional","affiliation":[{"name":"Pituitary Center, Department of Medicine, Cedars-Sinai Medical Center , Los Angeles, CA 90048 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens Otto L","family":"J\u00f8rgensen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Internal Medicine, Aarhus University Hospital , 8200 Aarhus ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne S","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Odense University Hospital , 5000 Odense ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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 ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne C","family":"Klose","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Copenhagen University Hospital Rigshospitalet , 2100 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5903-3355","authenticated-orcid":false,"given":"Ulla","family":"Feldt-Rasmussen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Copenhagen University Hospital Rigshospitalet , 2100 Copenhagen ,","place":["Denmark"]},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen , 2200 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander H","family":"Sparre-Ulrich","sequence":"additional","affiliation":[{"name":"Antag Therapeutics Aps , 2200 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9600-3254","authenticated-orcid":false,"given":"Mette M","family":"Rosenkilde","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen , 2200 Copenhagen 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