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Diabetologia
Published in: Diabetologia 10/2017

01-10-2017 | Article

Effects of insulin and exercise training on FGF21, its receptors and target genes in obesity and type 2 diabetes

Authors: Rikke Kruse, Sara G. Vienberg, Birgitte F. Vind, Birgitte Andersen, Kurt Højlund

Published in: Diabetologia | Issue 10/2017

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Abstract

Aims/hypothesis

Pharmacological doses of FGF21 improve glucose tolerance, lipid metabolism and energy expenditure in rodents. Induced expression and secretion of FGF21 from muscle may increase browning of white adipose tissue (WAT) in a myokine-like manner. Recent studies have reported that insulin and exercise increase FGF21 in plasma. Obesity and type 2 diabetes are potentially FGF21-resistant states, but to what extent FGF21 responses to insulin and exercise training are preserved, and whether FGF21, its receptors and target genes are altered, remains to be established.

Methods

The effects of insulin during euglycaemic–hyperinsulinaemic clamps and 10 week endurance training on serum FGF21 were examined in individuals with type 2 diabetes and in glucose tolerant overweight/obese and lean individuals. Gene expression of FGF21, its receptors and target genes in muscle and WAT biopsies was evaluated by quantitative real-time PCR (qPCR).

Results

Insulin increased serum and muscle FGF21 independent of overweight/obesity or type 2 diabetes, and there were no effects associated with exercise training. The insulin-induced increases in serum FGF21 and muscle FGF21 expression correlated tightly (p < 0.001). In WAT, overweight/obesity with and without type 2 diabetes led to reduced expression of KLB, but increased FGFR1c expression. However, the expression of most FGF21 target genes was unaltered except for reduced CIDEA expression in individuals with type 2 diabetes.

Conclusions/interpretation

Insulin-induced expression of muscle FGF21 correlates strongly with a rise in serum FGF21, and this response appears intact in overweight/obesity and type 2 diabetes. FGF21 resistance may involve reduced KLB expression in WAT. However, increased FGFR1c expression or other mechanisms seem to ensure adequate expression of most FGF21 target genes in WAT.
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Metadata
Title
Effects of insulin and exercise training on FGF21, its receptors and target genes in obesity and type 2 diabetes
Authors
Rikke Kruse
Sara G. Vienberg
Birgitte F. Vind
Birgitte Andersen
Kurt Højlund
Publication date
01-10-2017
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 10/2017
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-017-4373-5

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