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.

• Authors: J Zhang, H Li, N Bai, Y Xu, Q Song, L Zhang, G Wu, S Chen, X Hou, C Wang, L Wei, A Xu, Q Fang, W Jia
• Journal: Journal of endocrinological investigation (J Endocrinol Invest) Vol. 42 Issue 9 Pg. 1019-1027 (Sep 2019) ISSN: 1720-8386 [Electronic] Italy
• PMID: 30852757 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Blood Glucose
• FGF19 protein, human
• Insulin
• Fibroblast Growth Factors

Topics

• Adult
• Biomarkers (analysis)
• Blood Glucose (analysis)
• Fasting (physiology)
• Female
• Fibroblast Growth Factors (metabolism)
• Follow-Up Studies
• Glucose Clamp Technique
• Glucose Intolerance (physiopathology)
• Glucose Tolerance Test
• Humans
• Insulin (metabolism)
• Insulin Resistance
• Male
• Middle Aged
• Prognosis