Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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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 -