Plasma FGF21 concentrations are regulated by glucose independently of insulin and GLP-1 in lean, healthy humans
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Plasma FGF21 concentrations are regulated by glucose independently of insulin and GLP-1 in lean, healthy humans. / Solomon, Thomas P.J.; Carter, Steven; Haus, Jacob M.; Karstoft, Kristian; Von Holstein-Rathlou, Stephanie; Nielsen, Mette S.; Gillum, Matthew P.
In: PeerJ, Vol. 10, e12755, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Plasma FGF21 concentrations are regulated by glucose independently of insulin and GLP-1 in lean, healthy humans
AU - Solomon, Thomas P.J.
AU - Carter, Steven
AU - Haus, Jacob M.
AU - Karstoft, Kristian
AU - Von Holstein-Rathlou, Stephanie
AU - Nielsen, Mette S.
AU - Gillum, Matthew P.
N1 - Publisher Copyright: © 2022 PeerJ Inc.. All rights reserved.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Clamp methodology
KW - FGF21 secretion
KW - Fibroblast growth factor 21
KW - Incretin hormones
KW - Secretagogue
U2 - 10.7717/peerj.12755
DO - 10.7717/peerj.12755
M3 - Journal article
C2 - 35111398
AN - SCOPUS:85123114838
VL - 10
JO - PeerJ
JF - PeerJ
SN - 2167-8359
M1 - e12755
ER -
ID: 291123967