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FGF21 Is an Insulin-Dependent Postprandial Hormone in Adult Humans

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FGF21 Is an Insulin-Dependent Postprandial Hormone in Adult Humans. / Samms, Ricardo J; Lewis, Jo E; Norton, Luke; Stephens, Francis B; Gaffney, Christopher J; Butterfield, Tony; Smith, Dennis P; Cheng, Christine C; Perfield, James W; Adams, Andrew C; Ebling, Francis J P; Tsintzas, Kostas.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 102, No. 10, 01.10.2017, p. 3806-3813.

Research output: Contribution to journalJournal article

Harvard

Samms, RJ, Lewis, JE, Norton, L, Stephens, FB, Gaffney, CJ, Butterfield, T, Smith, DP, Cheng, CC, Perfield, JW, Adams, AC, Ebling, FJP & Tsintzas, K 2017, 'FGF21 Is an Insulin-Dependent Postprandial Hormone in Adult Humans', Journal of Clinical Endocrinology and Metabolism, vol. 102, no. 10, pp. 3806-3813. https://doi.org/10.1210/jc.2017-01257

APA

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. (2017). FGF21 Is an Insulin-Dependent Postprandial Hormone in Adult Humans. Journal of Clinical Endocrinology and Metabolism, 102(10), 3806-3813. https://doi.org/10.1210/jc.2017-01257

Vancouver

Samms RJ, Lewis JE, Norton L, Stephens FB, Gaffney CJ, Butterfield T et al. FGF21 Is an Insulin-Dependent Postprandial Hormone in Adult Humans. Journal of Clinical Endocrinology and Metabolism. 2017 Oct 1;102(10):3806-3813. https://doi.org/10.1210/jc.2017-01257

Author

Samms, Ricardo J ; Lewis, Jo E ; Norton, Luke ; Stephens, Francis B ; Gaffney, Christopher J ; Butterfield, Tony ; Smith, Dennis P ; Cheng, Christine C ; Perfield, James W ; Adams, Andrew C ; Ebling, Francis J P ; Tsintzas, Kostas. / FGF21 Is an Insulin-Dependent Postprandial Hormone in Adult Humans. In: Journal of Clinical Endocrinology and Metabolism. 2017 ; Vol. 102, No. 10. pp. 3806-3813.

Bibtex

@article{586644c7bf4a45cdb28a103f907d693c,
title = "FGF21 Is an Insulin-Dependent Postprandial Hormone in Adult Humans",
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.",
keywords = "Adult, Blood Glucose, Diabetes Mellitus, Type 2, Diet, High-Fat, Female, Fibroblast Growth Factors, Glucose, Glucose Clamp Technique, Glucose Tolerance Test, Humans, Insulin, Male, Middle Aged, Postprandial Period, Signal Transduction, Young Adult, Controlled Clinical Trial, Journal Article",
author = "Samms, {Ricardo J} and Lewis, {Jo E} and Luke Norton and Stephens, {Francis B} and Gaffney, {Christopher J} and Tony Butterfield and Smith, {Dennis P} and Cheng, {Christine C} and Perfield, {James W} and Adams, {Andrew C} and Ebling, {Francis J P} and Kostas Tsintzas",
year = "2017",
month = oct,
day = "1",
doi = "10.1210/jc.2017-01257",
language = "English",
volume = "102",
pages = "3806--3813",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "Oxford University Press",
number = "10",

}

RIS

TY - JOUR

T1 - FGF21 Is an Insulin-Dependent Postprandial Hormone in Adult Humans

AU - Samms, Ricardo J

AU - Lewis, Jo E

AU - Norton, Luke

AU - Stephens, Francis B

AU - Gaffney, Christopher J

AU - Butterfield, Tony

AU - Smith, Dennis P

AU - Cheng, Christine C

AU - Perfield, James W

AU - Adams, Andrew C

AU - Ebling, Francis J P

AU - Tsintzas, Kostas

PY - 2017/10/1

Y1 - 2017/10/1

N2 - 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.

AB - 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.

KW - Adult

KW - Blood Glucose

KW - Diabetes Mellitus, Type 2

KW - Diet, High-Fat

KW - Female

KW - Fibroblast Growth Factors

KW - Glucose

KW - Glucose Clamp Technique

KW - Glucose Tolerance Test

KW - Humans

KW - Insulin

KW - Male

KW - Middle Aged

KW - Postprandial Period

KW - Signal Transduction

KW - Young Adult

KW - Controlled Clinical Trial

KW - Journal Article

U2 - 10.1210/jc.2017-01257

DO - 10.1210/jc.2017-01257

M3 - Journal article

C2 - 28938434

VL - 102

SP - 3806

EP - 3813

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 10

ER -