Decrease of FGF19 contributes to the increase of fasting glucose in human in an insulin-independent manner

Abstract

Purpose: The ileum-derived fibroblast growth factor 19 (FGF19) plays key roles in hepatic glucose homeostasis in animals in an insulin-independent manner. Here, we analyzed the association of FGF19 with glucose effectiveness (GE, the insulin-independent glucose regulation), as well as hepatic glucose production (HGP) in Chinese subjects.

Methods: GE was measured by frequently sampled intravenous glucose tolerance test (FSIVGTT) in normal glucose tolerance (NGT), isolated-impaired glucose tolerance (I-IGT), and isolated-impaired fasting glucose (I-IFG) subjects. The oral glucose tolerance test-derived surrogate of GE (oGE) was determined in NGT, I-IFG, combined glucose intolerance (CGI), and type 2 diabetes (T2DM) subjects. HGP was assessed by labeled ([3-³H]-glucose) hyperinsulinemic-euglycemic clamp in NGT subjects. Insulin secretion and sensitivity were calculated by the hyperglycemic and hyperinsulinemic-euglycemic clamps in a subgroup of NGT, I-IGT, and I-IFG subjects. Serum FGF19 levels were determined by ELISA.

Results: FGF19 positively correlated with GE (r = 0.29, P = 0.004) as determined by FSIVGTT. The result was further confirmed by oGE (r = 0.261, P < 0.001). FGF19 was negatively associated with FPG (r = - 0.228, P = 0.025), but the association no longer existed after adjusting for GE (r = - 0.177, P = 0.086). FGF19 was negatively associated with basal HGP (r = - 0.697, P = 0.006). However, the correlation between FGF19 and insulin secretion and sensitivity were not found.

Conclusions: FGF19 levels are associated positively with GE and negatively with HGP. The increase of FPG in human is at least partially due to the decrease of FGF19 in an insulin-independent manner.

Keywords: Fasting glucose; Fibroblast growth factor 19; Glucose effectiveness; Glucose tolerance state; Hepatic glucose production.