FGF21 Is an Insulin-Dependent Postprandial Hormone in Adult Humans
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Context: Fibroblast growth factor 21 (FGF21) secretion has been shown to respond directly to carbohydrate consumption, with glucose, fructose, and sucrose all reported to increase plasma levels of FGF21 in rodents and humans. However, carbohydrate consumption also results in secretion of insulin. Objective: The aim of this study was to examine the combined and independent effects of hyperglycemia and hyperinsulinemia on total and bioactive FGF21 in the postprandial period in humans, and determine whether this effect is attenuated in conditions of altered insulin secretion and action. Methods: Circulating glucose, insulin, total and bioactive FGF21, and fibroblast activation protein were measured in adults with and without type 2 diabetes (T2D) following an oral glucose tolerance test (OGTT), and under a series of insulin and glucose clamp conditions and following high-fat diet in healthy adults. Results: Circulating total and bioactive FGF21 levels responded acutely to OGTT, and their ratio was attenuated in T2D patients with reduced postprandial insulin response. The clamp studies revealed that insulin but not glucose accounts for the postprandial rise in FGF21. Finally, there was an attenuated rise in FGF21 in response to a high-fat dietary intervention that is known to alter insulin-stimulated substrate utilization in metabolically active tissues. Conclusions: Insulin rather than glucose per se increases total and bioactive FGF21 in the postprandial period in adult humans. Understanding the impact of T2D on bioactive FGF21 will have a significant effect upon the efficacy of therapeutic agents designed to target the FGF21 pathway.
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Plasma FGF21 levels are induced by increases in both glucose and insulin levels in humans.
“In addition, in humans, plasma FGF21 levels have been shown to be induced by increases in both glucose and insulin levels (31, 84, 110, 133), supporting a role during refeeding.”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [110]
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The Regulation of Circulating Hepatokines by Fructose Ingestion in Humans
Richter, M. M., & Plomgaard, P. (2021) · Journal of the Endocrine Society · doi:10.1210/jendso/bvab121 · Cited by 7 · see citing works
Li, X., Zheng, K., Gu, W., Hou, X., Guan, Y., Liu, L., Hou, L., Geng, J., & Song, G. (2023) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s410457 · Cited by 7 · see citing works
Taniguchi, H., Nirengi, S., Ishihara, K., & Sakane, N. (2022) · PLoS ONE · doi:10.1371/journal.pone.0263774 · Cited by 7 · see citing works
Research Progress of Fibroblast Growth Factor 21 in Fibrotic Diseases
Jia, M.-Q., Guan, C., Tao, J., & Zhou, Y. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/5042762 · Cited by 7 · see citing works
Hazebroek, M. K., & Keipert, S. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.909621 · Cited by 6 · see citing works
Effects of central FGF21 infusion on the glucose homeostasis in rats (brain–pancreas axis)
Tanbek, K., Yılmaz, Ü., Gül, M., Koç, A., & Sandal, S. (2023) · Archives of Physiology and Biochemistry · doi:10.1080/13813455.2023.2166964 · Cited by 6 · see citing works
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The Relation Between Fibroblast Growth Factor 21 and Insulin Resistance in hyperlipidemia Patients
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FGF21 Levels in Pheochromocytoma/Functional Paraganglioma
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The Influence of Hyperglycemia on Liver Triglyceride Deposition in Partially Pancreatectomized Rats
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Early Hepatic Signals of Fat Overload
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The value of fibroblast growth factor 21 in health and pathology
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Tissue origins of the plasma proteomic response to glucose ingestion in humans
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For Weight Loss: Why Do GLP-1 Agonists Work, and How Can We Make Them Work Better?
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- Authors
- Samms, R. J., Lewis, J. E., Norton, L., Stephens, F. B., Gaffney, C. J., Butterfield, T., Smith, D. P., Cheng, C. C., Perfield, J. W., Adams, A. C., Ebling, F. J. P., & Tsintzas, K.
- Affiliations
- University of Nottingham (GB)
- The University of Texas at San Antonio Health Science Center (US)
- University of Exeter (GB)
- Eli Lilly (United States) (US)
- Corresponding author
- Tsintzas, Kostas
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2017-08-04
- Volume
- 102
- Issue
- 10
- Pages
- 3806-3813
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC5630254
- OpenAlex
- W2745100419
- Cited by
- 65
- References
- 40
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 9 · 2022: 10 · 2021: 11 · 2020: 5 · 2019: 15 · 2018: 6 · 2017: 1
- FWCI
- 3.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Open Research Exeter (University of Exeter) (acceptedVersion)
- Lancaster EPrints (Lancaster University) (submittedVersion)
- Nottingham ePrints (University of Nottingham) (submittedVersion, cc-by)
- Figshare (submittedVersion)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
- Funders
- Biotechnology and Biological Sciences Research Council (BB/M001555/1, BB/M021629/1)
- Diabetes UK (13/0004659)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Rheumatology › GDF15 and Related Biomarkers
- Keywords
- FGF21, insulin, postprandial hormone secretion, hyperglycemia, hyperinsulinemia, type 2 diabetes, oral glucose tolerance test, insulin clamp, high-fat diet, fibroblast activation protein, carbohydrate metabolism
- MeSH terms
- Adult, Blood Glucose, Diabetes Mellitus, Type 2, Female, Fibroblast Growth Factors, Glucose, Glucose Tolerance Test, Humans, Insulin, Male, Middle Aged, Glucose Clamp Technique, Signal Transduction, Postprandial Period, Young Adult, Diet, High-Fat
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