Dynamic Change of Serum FGF21 Levels in Response to Glucose Challenge in Human

Abstract

Fibroblast growth factor 21 (FGF21), an endocrine factor predominantly secreted from liver, possesses multiple beneficial effect on energy metabolism and insulin sensitivity in animals. This study aimed to investigate the acute change of serum FGF21 in response to glucose challenge in humans. A 75-g oral glucose tolerance test was performed among 20 healthy subjects, 18 with impaired glucose tolerance (IGT) and 21 with type 2 diabetes mellitus (T2DM). Blood samples were collected for measurement of FGF21 and other biochemical parameters. The associations of FGF21 with insulin and other metabolic parameters were analyzed. Fasting serum FGF21 levels increased progressively from healthy, IGT to T2DM subjects (P < 0.05 for global trend). After oral glucose administration, the serum FGF21 level showed a similar biphasic change in all three groups. It declined to a nadir level at 60 min and then increased gradually to its peak level at 180 min. FGF21 levels at different time points of oral glucose tolerance test negatively correlated with glucose levels in all subjects, and the fold change of serum FGF21 at different time points (compared with the basal level) were inversely associated with fold changes of insulin (P = 0.012) and C-peptide (P = 0.043) levels in healthy subjects but not in IGT and T2DM patients. The dynamic change of circulating FGF21 was associated with alterations in insulin levels in response to glucose challenge in humans. These findings support the role of FGF21 as a potential regulator of insulin secretion and glucose metabolism in humans.