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Here, we set out to identify novel triggers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We started with using metabolomics on plasma samples from meal tests in adults, where we identified sphinganine, a sphingolipid, as the strongest predictor of a high GLP-1 response. Sphinganine was next tested in vitro (in GLUTag and NCI-H716 cell lines and human intestinal organoids), ex vivo (in isolated rat intestinal and colon perfusion models) and in vivo (using both single acute administration and prolonged feeding in mice).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Sphinganine doubled GLP-1 secretion in vitro in multiple cell lines and human intestinal organoids, via G-protein-coupled receptor 40-mediated mechanisms. In isolated intestinal perfusion model in rats, sphinganine increased GLP-1 during luminal administration. However, this effect was only statistically significant in male rats. In vivo, oral administration of sphinganine to mice did not increase GLP-1 acutely or after prolonged feeding. In the prolonged-feeding model, however, it did reduce high-fat-diet-induced weight gain, without changing food intake.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\/interpretation<\/jats:title>\n                    <jats:p>Our data indicate beneficial metabolic effects of sphingolipids and points towards potential therapeutic effects to be explored.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00125-026-06877-1","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:16:45Z","timestamp":1790255805000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sphinganine as a novel stimulator of GLP-1 secretion"],"prefix":"10.1007","author":[{"given":"Mark M.","family":"Smits","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna K.","family":"Drzazga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarkko J.","family":"Lackman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Akhlef","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel A. 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Petersen (Department of Biomedical Sciences, University of Copenhagen) for technical help with the cell experiments and L. Alb\u00e6k (Department of Biomedical Sciences, University of Copenhagen) for laboratory assistance. This study was presented in abstract form at the 26th European Congress of Endocrinology (2024).","order":1,"name":"Ethics","label":"Acknowledgements","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"The data supporting the findings of this study are available upon request, by emailing the corresponding author with an outline of the intended use of the data. Data will be available from the date of publication and will remain available for the foreseeable future.","order":2,"name":"Ethics","label":"Data availability","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"This work was funded by the Lundbeck Foundation and EFSD. MMS received an Amsterdam Cardiovascular Sciences postdoc grant to cover salary for this project and a travel grant from BioScientifica Trust for training related to this project. Work in the Jensen group is supported by a grant from the Novo Nordisk Foundation (NNF23CC0084611). The Novo Nordisk Foundation Center for Stem Cell Medicine was supported by a Novo Nordisk Foundation grant (NNF21CC0073729). The study sponsors\/funders were not involved in the design of the study; the collection, analysis, and interpretation of data; writing the report; and did not impose any restrictions regarding the publication of the report.","order":3,"name":"Ethics","label":"Funding","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"MMS and JJH had advisory roles for Novo Nordisk. The other authors declare that there are no 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":"MMS and JJH conceived the study. The methodology was developed by MMS, AKD, VG, KBJ, TJG, MMR, JJH and OHN. The investigation was conducted by MMS, AKD, MA, JJL, SAJT, AMB, AL and SB. Resources were provided by OHN, VG, MMR and JJH. MMS, JJH and MMR prepared the original draft of the manuscript. MMS, AKD, MA, JJL, SAJT, AMB, KBJ, VG, AL, SB, TJG, OHN, MMR and JJH reviewed and edited the manuscript. MMS prepared the visualisations. MMR and JJH supervised the study. Funding was acquired by MMS, VG, MMR and JJH. All authors approved the final version of the manuscript for publication. MMS is responsible for the integrity of the work as a whole.","order":5,"name":"Ethics","label":"Contribution statement","group":{"name":"EthicsHeading","label":"Ethics"}}]}}