{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T12:29:16Z","timestamp":1793104156504,"version":"4.5.0"},"reference-count":64,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T00:00:00Z","timestamp":1705363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Obesity is a risk factor for cardiometabolic diseases. Nutrients stimulate GLP-1 release; however, GLP-1 has a short half-life (&lt;2 min), and only &lt;10\u201315% reaches the systemic circulation. Human L-cells are localized in the distal ileum and colon, while most nutrients are absorbed in the proximal intestine. We hypothesized that combinations of amino acids and fatty acids potentiate GLP-1 release via different L-cell receptors. GLP-1 secretion was studied in the mouse enteroendocrine STC-1 cells. Cells were pre-incubated with buffer for 1 h and treated with nutrients: alpha-linolenic acid (\u03b1LA), phenylalanine (Phe), tryptophan (Trp), and their combinations \u03b1LA+Phe and \u03b1LA+Trp with dipeptidyl peptidase-4 (DPP4) inhibitor. After 1 h GLP-1 in supernatants was measured and cell lysates taken for qPCR. \u03b1LA (12.5 \u00b5M) significantly stimulated GLP-1 secretion compared with the control. Phe (6.25\u201325 mM) and Trp (2.5\u201310 mM) showed a clear dose response for GLP-1 secretion. The combination of \u03b1LA (6.25 \u00b5M) and either Phe (12.5 mM) or Trp (5 mM) significantly increased GLP-1 secretion compared with \u03b1LA, Phe, or Trp individually. The combination of \u03b1LA and Trp upregulated GPR120 expression and potentiated GLP-1 secretion. These nutrient combinations could be used in sustained-delivery formulations to the colon to prolong GLP-1 release for diminishing appetite and preventing obesity.<\/jats:p>","DOI":"10.3390\/ijms25021087","type":"journal-article","created":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T04:03:30Z","timestamp":1705377810000},"page":"1087","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Nutrient Combinations Sensed by L-Cell Receptors Potentiate GLP-1 Secretion"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3970-6417","authenticated-orcid":false,"given":"Nalini","family":"Sodum","sequence":"first","affiliation":[{"name":"Research Unit of Biomedicine and Internal Medicine, Biocentre of Oulu, Medical Research Center, University of Oulu, Oulu University Hospital, Aapistie 5, 90220 Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orvokki","family":"Mattila","sequence":"additional","affiliation":[{"name":"Research Unit of Biomedicine and Internal Medicine, Biocentre of Oulu, Medical Research Center, University of Oulu, Oulu University Hospital, Aapistie 5, 90220 Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravikant","family":"Sharma","sequence":"additional","affiliation":[{"name":"Research Unit of Biomedicine and Internal Medicine, Biocentre of Oulu, Medical Research Center, University of Oulu, Oulu University Hospital, Aapistie 5, 90220 Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remi","family":"Kamakura","sequence":"additional","affiliation":[{"name":"Research Unit of Biomedicine and Internal Medicine, Biocentre of Oulu, Medical Research Center, University of Oulu, Oulu University Hospital, Aapistie 5, 90220 Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8153-1070","authenticated-orcid":false,"given":"Vesa-Pekka","family":"Lehto","sequence":"additional","affiliation":[{"name":"Department of Technical Physics, Faculty of Science, Forestry and Technology, University of Eastern Finland, 70210 Kuopio, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5813-5707","authenticated-orcid":false,"given":"Jaroslaw","family":"Walkowiak","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, 60572 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4460-2604","authenticated-orcid":false,"given":"Karl-Heinz","family":"Herzig","sequence":"additional","affiliation":[{"name":"Research Unit of Biomedicine and Internal Medicine, Biocentre of Oulu, Medical Research Center, University of Oulu, Oulu University Hospital, Aapistie 5, 90220 Oulu, Finland"},{"name":"Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, 60572 Pozna\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4590-456X","authenticated-orcid":false,"given":"Ghulam Shere","family":"Raza","sequence":"additional","affiliation":[{"name":"Research Unit of Biomedicine and Internal Medicine, Biocentre of Oulu, Medical Research Center, University of Oulu, Oulu University Hospital, Aapistie 5, 90220 Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.cmet.2021.12.012","article-title":"Why Does Obesity Cause Diabetes?","volume":"34","author":"Klein","year":"2022","journal-title":"Cell Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1161\/CIRCRESAHA.115.306883","article-title":"Obesity and Cardiovascular Disease","volume":"118","author":"Ortega","year":"2016","journal-title":"Circ. 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