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M\u00f8ller og Hustru Chastine Mc-Kinney M\u00f8llers Fond til almene Formaal","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005747","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001734","name":"Copenhagen University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001734","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Diabetologia"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims\/hypothesis<\/jats:title>\n                    <jats:p>\n                      In healthy lean humans, endogenous glucose-dependent insulinotropic polypeptide (GIP) contributes significantly to the postprandial increase in arteria mesenterica superior blood flow. The vascular biology related to activation of the GIP receptor is markedly impaired in individuals with type 2 diabetes and is sometimes absent. In this population, we investigated the role of endogenous GIP on postprandial splanchnic blood flow by using the GIP receptor antagonist, GIP(3-30)NH\n                      <jats:sub>2<\/jats:sub>\n                      . The primary outcome of this study was the changes in blood flow in arteria mesenterica superior during oral glucose with or without GIP receptor antagonist infusion.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Ten participants with type 2 diabetes (age 20\u201380 years, BMI 20\u201335 kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      , and HbA\n                      <jats:sub>1c<\/jats:sub>\n                      &gt;48 mmol\/mol and &lt;75 mmol\/mol) were investigated in a randomised, placebo-controlled, crossover study. On four separate occasions, participants received the following treatment: oral glucose + i.v. GIP(3-30)NH\n                      <jats:sub>2<\/jats:sub>\n                      ; oral glucose + i.v. saline (154 mmol\/l NaCl); oral water + i.v. GIP(3-30)NH\n                      <jats:sub>2<\/jats:sub>\n                      ; oral water + i.v. saline. Participants were randomly assigned to intervention groups using (random.org). Participants were unaware of allocation, while investigators were aware. No additional allocation concealment procedures were used. During all four interventions, splanchnic blood flow was measured using phase-contrast MRI in the arteria mesenterica superior, truncus coeliacus and vena portae during oral glucose (75 g) or water ingestion. The study was conducted at Rigshospitalet, Copenhagen. Liver volume and oxygenation, as well as gallbladder volume, were assessed. Blood samples were collected and analysed for insulin, C-peptide, GIP, glucagon and glucose.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Oral glucose alone increased mean blood flow in arteria mesenterica superior by 57% (95% CI 26, 88) and this was 15% (95% CI \u22122, 32) lower during concomitant GIP receptor antagonist infusion,\n                      <jats:italic>p<\/jats:italic>\n                      =0.012. Infusion of GIP receptor antagonist during oral glucose treatment did also result in lower insulin secretion, C-peptide and C-peptide\/glucose ratio compared with saline infusion, whereas glucagon levels and plasma glucose were unaffected. Oral water did not affect any outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\/interpretation<\/jats:title>\n                    <jats:p>Endogenous GIP contributes to postprandially increased splanchnic blood flow in people with type 2 diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov NCT06426823<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Funding<\/jats:title>\n                    <jats:p>This work was supported by the Novo Nordisk Foundation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00125-026-06788-1","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T18:20:44Z","timestamp":1783016444000},"page":"2897-2910","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["GIP contributes to postprandial regulation of splanchnic blood supply in humans with type 2 diabetes: a randomised, single-blinded, placebo-controlled, crossover study"],"prefix":"10.1007","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5892-7859","authenticated-orcid":false,"given":"Rasmus S.","family":"Rasmussen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5934-038X","authenticated-orcid":false,"given":"Sophie W.","family":"Nielsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lotte","family":"Alstrup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanne S. 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Elkington, A. L. Heidelbach and M. K. Federspiel for excellent MRI technical and practical assistance at the Department of Clinical Physiology and Nuclear Medicine Rigshospitalet, as well as S. N. Alkaabi, J. B. Fredslund and V. H. W. Petersen for flow data acquisition at the Department of Clinical Physiology and Nuclear Medicine Rigshospitalet-Glostrup. Additional thanks for technical assistance with the analysis of blood samples go to L. Alb\u00e6k and A. Bjerregaard at the Department of Biomedical Sciences, University of Copenhagen.","order":1,"name":"Ethics","label":"Acknowledgements","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"The datasets generated during the current study are available from the corresponding author. Access will be granted to qualified researchers for non-commercial research purposes, subject to approval by the corresponding author and, where applicable, institutional or ethical guidelines. Requests should include a brief description of the proposed research and analysis plan. There are no time restrictions on availability, provided that data storage remains compliant with institutional policies. Data will not be shared if this would violate participant confidentiality or consent agreements. The software for calculating blood flow PCM techniques is available at\n                      \n                      . Liver and gallbladder volumes were determined using Total Segmentator (\n                      \n                      ). The MRI images are not publicly available due to privacy restrictions.","order":2,"name":"Ethics","label":"Data availability","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"This work was supported by Rigshospitalet-Glostrup, Capital Region of Denmark, Department of Biomedical Sciences, University of Copenhagen, Novo Nordisk Foundation grant NNF18SA0034956, The European Foundation for the Study of Diabetes, H\u00f8rslev Foundation, King Christian the 10th Foundation, A. P. M\u00f8ller Foundation (to LSG), Skibsreder Per Henriksen, R and Hustrus Foundation (to JJH), and The Danish Diabetes Association (to RSR).","order":3,"name":"Ethics","label":"Funding","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"JJH, MMR and LSG are founders of Antag Therapeutics. MMR, JJH and BHar are founders of Bainan Biotech. MMR and LSG are patent holders for GIP receptor antagonists and for dual GIP receptor\/GLP-2 receptor agonists. The authors declare that there are no other relationships or activities that might bias, or be perceived to bias, their work.","order":4,"name":"Ethics","label":"Authors\u2019 relationships and activities","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"RSR conducted the study, wrote the manuscript, conducted the statistical analyses and researched data. SWN, LA and TSWL conducted the study and reviewed and edited the manuscript. JKH and RPP generated data, and reviewed and edited the manuscript. MBV conducted the statistical analyses, developed the MRI analysis code, researched data and reviewed and edited the manuscript. BHar planned the study, analysed plasma samples and reviewed and edited the manuscript. HHJ researched data and reviewed and edited the manuscript. JJH initiated and supervised the study, generated data and reviewed and edited the manuscript. BHad conducted the study, planned the MRI analyses, researched data and reviewed and edited the manuscript. HBWL and MMR contributed to the interpretation of data, and critically reviewed and revised the manuscript for important intellectual content.\u00a0AA and UBA initiated and supervised the study and reviewed and edited the manuscript. LSG planned and supervised the study, acquired funding, wrote the manuscript and researched data. All authors approved the final version of the manuscript for publication. LSG is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.","order":5,"name":"Ethics","label":"Contribution statement","group":{"name":"EthicsHeading","label":"Ethics"}}]}}