Fibroblast growth factor-21 is induced in human skeletal muscles by hyperinsulinemia.
OBJECTIVE
Fibroblast growth factor-21 (FGF-21) is a potent metabolic regulator, which in animal models has been shown to improve glucose metabolism and insulin sensitivity. Recently, FGF-21 was shown to be expressed and secreted from murine muscle cells in response to insulin stimulation.


METHODS
We studied muscular FGF-21 expression and plasma FGF-21 after acute insulin stimulation in young healthy men during a hyperinsulinemic-euglycemic clamp. Furthermore, we investigated systemic levels and muscle FGF-21 expression in humans with or without insulin resistance and chronic elevated insulin.


RESULTS
FGF-21 was barely detectable in young healthy men before insulin infusion. After 3 or 4 h of insulin infusion during a hyperinsulinemic-euglycemic clamp, muscular FGF-21 expression increased significantly. Plasma FGF-21 followed the same pattern. In individuals with chronic elevated insulin, muscular FGF-21 expression was associated with hyperinsulinemia in men but not in women. In plasma, hyperinsulinemia and fasting glucose were positively associated with plasma FGF-21 while plasma FGF-21 correlated negatively with HDL cholesterol. No associations between muscle and plasma FGF-21 were found in the individuals with chronic hyperinsulinemia.


CONCLUSIONS
FGF-21 is expressed in human skeletal muscle in response to insulin stimulation, suggesting that FGF-21 is an insulin-regulated myokine. In support, we found an association between chronic hyperinsulinemia and levels of FGF-21.
Hojman
Pernille
P
Department of Infectious Diseases, Centre of Inflammation and Metabolism, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. pernille.hoejman.moeller@rh.regionh.dk
Pedersen
Maria
M
Nielsen
Anders Rinnov
AR
Krogh-Madsen
Rikke
R
Yfanti
Christina
C
Akerstrom
Thorbjørn
T
Nielsen
Søren
S
Pedersen
Bente Klarlund
BK
D000208:Acute Disease; D001706:Biopsy; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005215:Fasting; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood / Q000378:metabolism*; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000378:metabolism*; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D016014:Linear Models; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D055815:Young Adult
D001786:Blood Glucose; D007328:Insulin; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors