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J Clin Endocrinol Metab. 2017 Oct 1;102(10):3806-3813. doi: 10.1210/jc.2017-01257.

FGF21 Is an Insulin-Dependent Postprandial Hormone in Adult Humans.

Author information

1
School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom.
2
Lilly Research Laboratories, Indianapolis, Indiana 46285.
3
Diabetes Division, University of Texas Health Science Center, San Antonio, Texas 78229.
4
Department of Sport and Health Sciences, University of Exeter, Exeter EX1 2LU, United Kingdom.

Abstract

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.

PMID:
28938434
PMCID:
PMC5630254
DOI:
10.1210/jc.2017-01257
[Indexed for MEDLINE]
Free PMC Article

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