Fibroblast growth factor-21 is induced in human skeletal muscles by hyperinsulinemia

TY - JOUR

T1 - Fibroblast growth factor-21 is induced in human skeletal muscles by hyperinsulinemia

AU - Hojman, Pernille

AU - Pedersen, Maria

AU - Nielsen, Anders Rinnov

AU - Krogh-Madsen, Rikke

AU - Yfanti, Christina

AU - Åkerström, Thorbjörn

AU - Nielsen, Søren

AU - Pedersen, Bente Klarlund

N1 - Keywords: Acute Disease; Biopsy; Blood Glucose; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Fasting; Female; Fibroblast Growth Factors; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Linear Models; Male; Muscle, Skeletal; Polymerase Chain Reaction; Young Adult

PY - 2009

Y1 - 2009

N2 - 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. RESEARCH DESIGN AND 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.

AB - 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. RESEARCH DESIGN AND 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.

U2 - 10.2337/db09-0713

DO - 10.2337/db09-0713

M3 - Journal article

C2 - 19720803

SN - 0012-1797

VL - 58

SP - 2797

EP - 2801

JO - Diabetes

JF - Diabetes

IS - 12

ER -