Hojman Pernille, Pedersen Maria, Nielsen Anders Rinnov, Krogh-Madsen Rikke, Yfanti Christina, Akerstrom Thorbjørn, Nielsen Søren, Pedersen Bente Klarlund
Department of Infectious Diseases, Centre of Inflammation and Metabolism, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Diabetes. 2009 Dec;58(12):2797-801. doi: 10.2337/db09-0713. Epub 2009 Aug 31.
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.
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.
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.
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.
成纤维细胞生长因子21（FGF - 21）是一种强效的代谢调节因子，在动物模型中已显示其可改善葡萄糖代谢和胰岛素敏感性。最近，研究表明FGF - 21在胰岛素刺激下由小鼠肌肉细胞表达并分泌。
我们在高胰岛素 - 正常血糖钳夹实验中研究了年轻健康男性急性胰岛素刺激后肌肉FGF - 21的表达及血浆FGF - 21水平。此外，我们还调查了有无胰岛素抵抗及慢性胰岛素水平升高的人群的全身FGF - 21水平和肌肉FGF - 21表达情况。
在年轻健康男性胰岛素输注前，FGF - 21几乎检测不到。在高胰岛素 - 正常血糖钳夹实验中胰岛素输注3或4小时后，肌肉FGF - 21表达显著增加。血浆FGF - 21呈现相同模式。在慢性胰岛素水平升高的个体中，男性肌肉FGF - 21表达与高胰岛素血症相关，而女性则不然。在血浆中，高胰岛素血症和空腹血糖与血浆FGF - 21呈正相关，而血浆FGF - 21与高密度脂蛋白胆固醇呈负相关。在慢性高胰岛素血症个体中未发现肌肉和血浆FGF - 21之间存在关联。
FGF - 21在胰岛素刺激下在人类骨骼肌中表达，提示FGF - 21是一种受胰岛素调节的肌动蛋白。作为支持，我们发现慢性高胰岛素血症与FGF - 21水平之间存在关联。
