Plasma FGF21 concentrations are regulated by glucose independently of insulin and GLP-1 in lean, healthy humans
Background 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 p...
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PeerJ Inc.
2022-01-01
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| author | Thomas P.J. Solomon Steven Carter Jacob M. Haus Kristian Karstoft Stephanie von Holstein-Rathlou Mette S. Nielsen Matthew P. Gillum |
| author_facet | Thomas P.J. Solomon Steven Carter Jacob M. Haus Kristian Karstoft Stephanie von Holstein-Rathlou Mette S. Nielsen Matthew P. Gillum |
| author_sort | Thomas P.J. Solomon |
| collection | DOAJ |
| description | Background 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. Methods 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/m2/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. Results Plasma FGF21 was unaltered during hyperglycemic infusion and hyperinsulinemic euglycemic clamps, compared to baseline. FGF21 was, however, increased by hyperglycemia under pancreatic clamp conditions (P < 0.05), while GLP-1 infusion under pancreatic clamp conditions did not change circulating FGF21 levels. Conclusion Increases in plasma FGF21 are likely 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. |
| first_indexed | 2024-03-09T08:18:25Z |
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| language | English |
| last_indexed | 2024-03-09T08:18:25Z |
| publishDate | 2022-01-01 |
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| spelling | doaj.art-40920c536f364215a5a520f8500fb7dc2023-12-02T21:54:58ZengPeerJ Inc.PeerJ2167-83592022-01-0110e1275510.7717/peerj.12755Plasma FGF21 concentrations are regulated by glucose independently of insulin and GLP-1 in lean, healthy humansThomas P.J. Solomon0Steven Carter1Jacob M. Haus2Kristian Karstoft3Stephanie von Holstein-Rathlou4Mette S. Nielsen5Matthew P. Gillum6School of Sport, Exercise and Rehabilitation Sciences, College of Life & Environmental Sciences, University of Birmingham, Edgbaston, United KingdomSchool of Sport, Exercise and Rehabilitation Sciences, College of Life & Environmental Sciences, University of Birmingham, Edgbaston, United KingdomSchool of Kinesiology, University of Michigan - Ann Arbor, Michigan, United States of AmericaCentre of Inflammation and Metabolism, Rigshospitalet, Copenhagen, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkBackground 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. Methods 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/m2/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. Results Plasma FGF21 was unaltered during hyperglycemic infusion and hyperinsulinemic euglycemic clamps, compared to baseline. FGF21 was, however, increased by hyperglycemia under pancreatic clamp conditions (P < 0.05), while GLP-1 infusion under pancreatic clamp conditions did not change circulating FGF21 levels. Conclusion Increases in plasma FGF21 are likely 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.https://peerj.com/articles/12755.pdfFibroblast growth factor 21SecretagogueIncretin hormonesClamp methodologyFGF21 secretion |
| spellingShingle | Thomas P.J. Solomon Steven Carter Jacob M. Haus Kristian Karstoft Stephanie von Holstein-Rathlou Mette S. Nielsen Matthew P. Gillum Plasma FGF21 concentrations are regulated by glucose independently of insulin and GLP-1 in lean, healthy humans PeerJ Fibroblast growth factor 21 Secretagogue Incretin hormones Clamp methodology FGF21 secretion |
| title | Plasma FGF21 concentrations are regulated by glucose independently of insulin and GLP-1 in lean, healthy humans |
| title_full | Plasma FGF21 concentrations are regulated by glucose independently of insulin and GLP-1 in lean, healthy humans |
| title_fullStr | Plasma FGF21 concentrations are regulated by glucose independently of insulin and GLP-1 in lean, healthy humans |
| title_full_unstemmed | Plasma FGF21 concentrations are regulated by glucose independently of insulin and GLP-1 in lean, healthy humans |
| title_short | Plasma FGF21 concentrations are regulated by glucose independently of insulin and GLP-1 in lean, healthy humans |
| title_sort | plasma fgf21 concentrations are regulated by glucose independently of insulin and glp 1 in lean healthy humans |
| topic | Fibroblast growth factor 21 Secretagogue Incretin hormones Clamp methodology FGF21 secretion |
| url | https://peerj.com/articles/12755.pdf |
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