{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:22:07Z","timestamp":1783488127366,"version":"3.55.0"},"reference-count":42,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T00:00:00Z","timestamp":1642550400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001648","name":"The European Foundation for the Study of Diabetes","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001648","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000041","name":"The American Diabetes Association","doi-asserted-by":"crossref","award":["JMH: 1-14-JF-32"],"award-info":[{"award-number":["JMH: 1-14-JF-32"]}],"id":[{"id":"10.13039\/100000041","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Danish Council for Independent Research"},{"name":"The Novo Nordisk Foundation Center for Basic Metabolic Research"},{"name":"The Novo Nordisk Foundation Center for Basic Metabolic Research"},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"crossref","award":["NNF18CC0034900"],"award-info":[{"award-number":["NNF18CC0034900"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n               <jats:title>Background<\/jats:title>\n               <jats:p>Fibroblast growth factor 21 (FGF21) treatment improves metabolic homeostasis in diverse species, including humans. Physiologically, plasma FGF21 levels increase modestly after glucose ingestion, but it is unclear whether this is mediated by glucose itself or due to a secondary effect of postprandial endocrine responses. A refined understanding of the mechanisms that control FGF21 release in humans may accelerate the development of small-molecule FGF21 secretagogues to treat metabolic disease. This study aimed to determine whether FGF21 secretion is stimulated by elevations in plasma glucose, insulin, or glucagon-like peptide-1 (GLP-1) in humans.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Methods<\/jats:title>\n               <jats:p>Three groups of ten healthy participants were included in a parallel-group observational study. Group A underwent a hyperglycemic infusion; Group B underwent a 40 mU\/m<jats:sup>2<\/jats:sup>\/min hyperinsulinemic euglycemic clamp; Group C underwent two pancreatic clamps (to suppress endogenous insulin secretion) with euglycemic and hyperglycemic stages with an infusion of either saline or 0.5 pmol\/kg\/min GLP-1. Plasma FGF21 concentrations were measured at baseline and during each clamp stage by ELISA.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Results<\/jats:title>\n               <jats:p>Plasma FGF21 was unaltered during hyperglycemic infusion and hyperinsulinemic euglycemic clamps, compared to baseline. FGF21 was, however, increased by hyperglycemia under pancreatic clamp conditions (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05), while GLP-1 infusion under pancreatic clamp conditions did not change circulating FGF21 levels.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Conclusion<\/jats:title>\n               <jats:p>Increases in plasma FGF21 are <jats:italic>likely<\/jats:italic> driven directly by changes in plasma glucose independent of changes in insulin or GLP-1 secretion. Ecologically valid postprandial investigations are now needed to confirm our observations from basic science infusion models.<\/jats:p>\n            <\/jats:sec>","DOI":"10.7717\/peerj.12755","type":"journal-article","created":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T10:17:32Z","timestamp":1642587452000},"page":"e12755","source":"Crossref","is-referenced-by-count":10,"title":["Plasma FGF21 concentrations are regulated by glucose independently of insulin and GLP-1 in lean, healthy humans"],"prefix":"10.7717","volume":"10","author":[{"given":"Thomas P.J.","family":"Solomon","sequence":"first","affiliation":[{"name":"School of Sport, Exercise and Rehabilitation Sciences, College of Life & Environmental Sciences, University of Birmingham, Edgbaston, United Kingdom"},{"name":"Institute of Metabolism and Systems Research, College of Medical & Dental Sciences, University of Birmingham, Edgbaston, United 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