FGF21 is an insulin-dependent postprandial hormone in adult humans

Samms, Ricardo J. and Lewis, Jo E. and Norton, Luke and Stephens, Francis B. and Gaffney, Christopher J. and Butterfield, Tony and Smith, Dennis and Cheng, Christine and Perfield, James W. and Adams, Andrew C. and Ebling, Francis J.P. and Tsintzas, Kostas (2017) FGF21 is an insulin-dependent postprandial hormone in adult humans. Journal of Clinical Endocrinology & Metabolism . ISSN 0021-972X

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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 (FAPα) 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.

Item Type: Article
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Life Sciences
Identification Number: 10.1210/jc.2017-01257
Depositing User: Eprints, Support
Date Deposited: 17 Aug 2017 13:07
Last Modified: 24 Sep 2017 23:19
URI: http://eprints.nottingham.ac.uk/id/eprint/44969

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