{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T18:20:10Z","timestamp":1785522010675,"version":"3.56.0"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Hospital"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pituitary"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hypoglycaemia stimulates growth hormone (GH) secretion, whereas hyperglycaemia suppresses it. However, the underlying mechanisms are not fully understood, particularly the potential role of gut-derived hormones released in response to oral glucose.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To investigate whether GH suppression is modulated by the route of glucose administration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A two-day intervention study in healthy volunteers. GH, insulin, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) responses during a 2-h oral glucose tolerance test (OGTT) were compared with those during a 2-h isoglycaemic intravenous (IV) glucose infusion. GH levels were analyzed using paired t-test of GH concentrations at every blood sample time point. The effect of intervention on all measured hormones were also assessed by paired t-test of Area Under the Curve (AUC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>12 healthy volunteers (6 females, mean age 47.9\u2009\u00b1\u20095.4\u00a0years) were included. In 9 of the 12 subjects, IV glucose induced an early peak in plasma-GH followed by a decrease. At 20\u00a0min after glucose intake GH levels increased by 46% during IV glucose compared to a decrease of 17% during oral glucose. The biggest numerically difference in GH between oral vs IV glucose was seen at 45\u00a0min (median [range], 0.30 [0.05\u20131.13] vs. 0.46 [0.05\u20139.82] \u00b5g\/l, p\u2009=\u20090.072). There was no difference between AUC of GH levels (p\u2009=\u20090.381). During IV glucose, two subjects did not reach the threshold for excluding acromegaly. Oral glucose showed significant increases compared to IV glucose for insulin (p\u2009&lt;\u20090.001), GLP-1 (p\u2009=\u20090.002) and GIP (p\u2009&lt;\u20090.001) when using paired t-test of AUC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Route of glucose exposure might influence the suppressive effect of glucose on GH secretion. This finding suggests that stimulation of other hormone systems may play a contributing role on the regulation of GH. The potential mechanism behind remains elusive but changes in gut-derived hormones might be of importance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11102-025-01633-x","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T15:24:34Z","timestamp":1768231474000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Comparison of oral versus intravenous glucose exposure on plasma growth hormone levels: a crossover study in healthy volunteers"],"prefix":"10.1007","volume":"29","author":[{"given":"Anna Katarina","family":"Vinten","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanna Thurmann","family":"J\u00f8rgensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esben","family":"Budtz-J\u00f8rgensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Klose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikkel","family":"Andreassen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"issue":"3","key":"1633_CR1","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1159\/000497214","volume":"108","author":"M Hage","year":"2019","unstructured":"Hage M et al (2019) Growth hormone response to oral glucose load: from normal to pathological conditions. Neuroendocrinology 108(3):244\u2013255. https:\/\/doi.org\/10.1159\/000497214","journal-title":"Neuroendocrinology"},{"issue":"4","key":"1633_CR2","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1007\/s13300-023-01381-w","volume":"14","author":"K Heinla","year":"2023","unstructured":"Heinla K et al (2023) GLP-1 receptor agonists induce growth hormone secretion in healthy volunteers. Diabetes Ther 14(4):777\u2013786. https:\/\/doi.org\/10.1007\/s13300-023-01381-w","journal-title":"Diabetes Ther"},{"issue":"3","key":"1633_CR3","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1210\/clinem\/dgae583","volume":"110","author":"MH Jensen","year":"2025","unstructured":"Jensen MH et al (2025) GIP Receptor Antagonism Eliminates Paradoxical Growth Hormone Secretion in Some Patients With Acromegaly. J Clin Endocrinol Metab 110(3):715\u2013729. https:\/\/doi.org\/10.1210\/clinem\/dgae583","journal-title":"J Clin Endocrinol Metab"},{"issue":"7","key":"1633_CR4","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1111\/j.1365-2826.2011.02155.x","volume":"23","author":"G Occhi","year":"2011","unstructured":"Occhi G et al (2011) The glucose-dependent insulinotropic polypeptide receptor is overexpressed amongst GNAS1 mutation-negative somatotropinomas and drives growth hormone (GH)-promoter activity in GH3 cells. J Neuroendocrinol 23(7):641\u2013649. https:\/\/doi.org\/10.1111\/j.1365-2826.2011.02155.x","journal-title":"J Neuroendocrinol"},{"issue":"5","key":"1633_CR5","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1530\/EJE-16-0831","volume":"176","author":"D Regazzo","year":"2017","unstructured":"Regazzo D et al (2017) The GIP\/GIPR axis is functionally linked to GH-secretion increase in a significant proportion of Gsp\u2212 somatotropinomas. Eur J Endocrinol 176(5):543\u2013553. https:\/\/doi.org\/10.1530\/EJE-16-0831","journal-title":"Eur J Endocrinol"},{"issue":"1","key":"1633_CR6","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1007\/s11102-022-01297-x","volume":"26","author":"NT J\u00f8rgensen","year":"2023","unstructured":"J\u00f8rgensen NT et al (2023) Glucose metabolism, gut-brain hormones, and acromegaly treatment: an explorative single centre descriptive analysis. Pituitary 26(1):152\u2013163. https:\/\/doi.org\/10.1007\/s11102-022-01297-x","journal-title":"Pituitary"},{"issue":"1","key":"1633_CR7","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1210\/jcem-60-1-120","volume":"60","author":"T Krarup","year":"1985","unstructured":"Krarup T et al (1985) Immunoreactive gastric inhibitory polypeptide response to a meal during the first eighteen months after diagnosis of type 1 (Insulin Dependent) diabetes mellitus. J Clin Endocrinol Metab 60(1):120\u2013125. https:\/\/doi.org\/10.1210\/jcem-60-1-120","journal-title":"J Clin Endocrinol Metab"},{"issue":"8","key":"1633_CR8","doi-asserted-by":"publisher","first-page":"2519","DOI":"10.1210\/jc.2011-0266","volume":"96","author":"O Lindgren","year":"2011","unstructured":"Lindgren O et al (2011) Incretin hormone and insulin responses to oral versus intravenous lipid administration in humans. J Clin Endocrinol Metab 96(8):2519\u20132524. https:\/\/doi.org\/10.1210\/jc.2011-0266","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"1633_CR9","doi-asserted-by":"publisher","first-page":"202","DOI":"10.4183\/aeb.2015.202","volume":"11","author":"Aydin","year":"2015","unstructured":"Aydin et al (2015) Comparison of Growth Hormone Suppression Response after Oral and Intravenous Glucose Tolerance Tests in Healthy Adults. Acta Endo (Buc) 11(2):202\u2013207. https:\/\/doi.org\/10.4183\/aeb.2015.202","journal-title":"Acta Endo (Buc)"},{"issue":"3","key":"1633_CR10","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1042\/cs1030325","volume":"103","author":"E Nakagawa","year":"2002","unstructured":"Nakagawa E et al (2002) Hyperglycaemia suppresses the secretion of ghrelin, a novel growth-hormone-releasing peptide: responses to the intravenous and oral administration of glucose. Clin Sci 103(3):325\u2013328. https:\/\/doi.org\/10.1042\/cs1030325","journal-title":"Clin Sci"},{"issue":"3","key":"1633_CR11","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.yfrne.2013.07.005","volume":"34","author":"M Theodoropoulou","year":"2013","unstructured":"Theodoropoulou M, Stalla G\u00fcnterK (2013) Somatostatin receptors: from signaling to clinical practice. Front Neuroendocrinol 34(3):228\u2013252. https:\/\/doi.org\/10.1016\/j.yfrne.2013.07.005","journal-title":"Front Neuroendocrinol"},{"issue":"3","key":"1633_CR12","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.tem.2009.12.003","volume":"21","author":"A Ben-Shlomo","year":"2010","unstructured":"Ben-Shlomo A, Melmed S (2010) Pituitary somatostatin receptor signaling. Trends Endocrinol Metab 21(3):123\u2013133. https:\/\/doi.org\/10.1016\/j.tem.2009.12.003","journal-title":"Trends Endocrinol Metab"},{"issue":"4","key":"1633_CR13","doi-asserted-by":"publisher","first-page":"E412","DOI":"10.1152\/ajpendo.00104.2022","volume":"325","author":"BA Aulinger","year":"2023","unstructured":"Aulinger BA, D\u2019Alessio DA (2023) Assessment of the incretin effect in healthy subjects: concordance between clamp and OGTT methods. Am J Physiol Endocrinol Metab 325(4):E412\u2013E420. https:\/\/doi.org\/10.1152\/ajpendo.00104.2022","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"S3","key":"1633_CR14","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1111\/dom.14496","volume":"23","author":"MA Nauck","year":"2021","unstructured":"Nauck MA et al (2021) The evolving story of incretins (GIP and GLP-1) in metabolic and cardiovascular disease: a pathophysiological update. Diabetes Obes Metab 23(S3):5\u201329. https:\/\/doi.org\/10.1111\/dom.14496","journal-title":"Diabetes Obes Metab"},{"issue":"6","key":"1633_CR15","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1210\/jcem-60-6-1204","volume":"60","author":"GP Ceda","year":"1985","unstructured":"Ceda GP et al (1985) Regulation of growth-hormone release from cultured human pituitary-adenomas by somatomedins and insulin. J Clin Endocrinol Metab 60(6):1204\u20131209. https:\/\/doi.org\/10.1210\/jcem-60-6-1204","journal-title":"J Clin Endocrinol Metab"},{"issue":"7","key":"1633_CR16","doi-asserted-by":"publisher","first-page":"2239","DOI":"10.1210\/jcem.82.7.4071","volume":"82","author":"R Lanzi","year":"1997","unstructured":"Lanzi R et al (1997) Evidence for an inhibitory effect of physiological levels of insulin on the growth hormone (GH) response to GH-releasing hormone in healthy subjects. J Clin Endocrinol Metab 82(7):2239\u20132243. https:\/\/doi.org\/10.1210\/jcem.82.7.4071","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"1633_CR17","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.1159\/000493448","volume":"49","author":"MC V\u00e1zquez-Borrego","year":"2018","unstructured":"V\u00e1zquez-Borrego MC et al (2018) The pituitary gland is a novel major site of action of metformin in non-human primates: a potential path to expand and integrate its metabolic actions. Cell Physiol Biochem 49(4):1444\u20131459. https:\/\/doi.org\/10.1159\/000493448","journal-title":"Cell Physiol Biochem"},{"issue":"7","key":"1633_CR18","doi-asserted-by":"publisher","first-page":"2410","DOI":"10.1210\/en.2013-1261","volume":"154","author":"MD Gahete","year":"2013","unstructured":"Gahete MD et al (2013) Insulin and IGF-I inhibit GH synthesis and release in vitro and in vivo by separate mechanisms. Endocrinology 154(7):2410\u20132420. https:\/\/doi.org\/10.1210\/en.2013-1261","journal-title":"Endocrinology"},{"issue":"23","key":"1633_CR19","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232314899","volume":"23","author":"A Psilopanagioti","year":"2022","unstructured":"Psilopanagioti A et al (2022) Glucagon-like peptide-1 receptor in the human hypothalamus is associated with body mass index and colocalizes with the anorexigenic neuropeptide nucleobindin-2\/nesfatin-1. Int J Mol Sci 23(23):14899. https:\/\/doi.org\/10.3390\/ijms232314899","journal-title":"Int J Mol Sci"},{"issue":"12","key":"1633_CR20","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci11121647","volume":"11","author":"LN Deden","year":"2021","unstructured":"Deden LN et al (2021) Brain imaging of the GLP-1 receptor in obesity using 68Ga-NODAGA-Exendin-4 PET. Brain Sci 11(12):1647. https:\/\/doi.org\/10.3390\/brainsci11121647","journal-title":"Brain Sci"},{"issue":"6","key":"1633_CR21","doi-asserted-by":"publisher","first-page":"2131","DOI":"10.1053\/j.gastro.2007.03.054","volume":"132","author":"LL Baggio","year":"2007","unstructured":"Baggio LL, Drucker DJ (2007) Biology of incretins: GLP-1 and GIP. Gastroenterology 132(6):2131\u20132157. https:\/\/doi.org\/10.1053\/j.gastro.2007.03.054","journal-title":"Gastroenterology"},{"issue":"5","key":"1633_CR22","doi-asserted-by":"publisher","first-page":"1247","DOI":"10.1210\/en.2019-00074","volume":"160","author":"BK Mani","year":"2019","unstructured":"Mani BK et al (2019) Ghrelin\u2019s relationship to blood glucose. Endocrinology 160(5):1247\u20131261. https:\/\/doi.org\/10.1210\/en.2019-00074","journal-title":"Endocrinology"},{"issue":"11","key":"1633_CR23","doi-asserted-by":"publisher","first-page":"4255","DOI":"10.1210\/en.141.11.4255","volume":"141","author":"Y Date","year":"2000","unstructured":"Date Y et al (2000) Ghrelin, a Novel Growth Hormone-Releasing Acylated Peptide, Is Synthesized in a Distinct Endocrine Cell Type in the Gastrointestinal Tracts of Rats and Humans. Endocrinology (Philadelphia) 141(11):4255\u20134261. https:\/\/doi.org\/10.1210\/en.141.11.4255","journal-title":"Endocrinology (Philadelphia)"},{"issue":"1","key":"1633_CR24","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1146\/annurev-physiol-021115-105439","volume":"78","author":"FM Gribble","year":"2016","unstructured":"Gribble FM et al (2016) Enteroendocrine cells: chemosensors in the intestinal epithelium. Annu Rev Physiol 78(1):277\u2013299. https:\/\/doi.org\/10.1146\/annurev-physiol-021115-105439","journal-title":"Annu Rev Physiol"},{"issue":"1","key":"1633_CR25","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1210\/jcem.87.1.8129","volume":"87","author":"T Shiiya","year":"2002","unstructured":"Shiiya T et al (2002) Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metab 87(1):240\u2013244. https:\/\/doi.org\/10.1210\/jcem.87.1.8129","journal-title":"J Clin Endocrinol Metab"}],"container-title":["Pituitary"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11102-025-01633-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11102-025-01633-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11102-025-01633-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T17:38:22Z","timestamp":1773682702000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11102-025-01633-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,12]]},"references-count":25,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["1633"],"URL":"https:\/\/doi.org\/10.1007\/s11102-025-01633-x","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-7640938\/v1","asserted-by":"object"}]},"ISSN":["1386-341X","1573-7403"],"issn-type":[{"value":"1386-341X","type":"print"},{"value":"1573-7403","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,12]]},"assertion":[{"value":"17 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"28"}}