Decrease of FGF19 contributes to the increase of fasting glucose in human in an insulin-independent manner
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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.
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.
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.
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.
KeywordsFibroblast growth factor 19 Glucose tolerance state Glucose effectiveness Fasting glucose Hepatic glucose production
The authors would like to thank Junxi Lu, Wei Zhu, Yiting Shen, and Jia Wang (Shanghai Jiao Tong University Affiliated Sixth People’s Hospital) for excellent technical assistance. The authors gratefully acknowledge all of the involved clinicians, nurses, and technicians at Shanghai Jiao Tong University Affiliated Sixth People’s Hospital for their dedication in this study. The authors would also like to thank all the colleagues in the Metabolic Disease Biobank Resource at Shanghai Jiao Tong University Affiliated Sixth People’s Hospital for the technical support.
JZ designed the research, conducted the experiments, analyzed data, and wrote the manuscript. HL contributed to the study design and manuscript writing. NB, YX, QS, LZ, GW, SC, XH, CW, and LW performed research. AX was involved in revising the manuscript. QF designed the study, interpreted data, and revised the manuscript. WJ designed the study, revised the manuscript, and contributed to the discussion. All authors have made substantial contributions and approved the final version of the manuscript.
This work was supported by the National Natural Science Foundation major international (regional) joint research project (81220108006) to W.J., the Shanghai Natural Science Foundation (15ZR1431700) and Major Program of Shanghai Municipality for Basic Research (10JC1412400) to Q.F., and Young Scientists Fund of National Natural Science Foundation of China (81200292) to H.L.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Research involving human participants
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 5.Osei K, Rhinesmith S, Gaillard T, Schuster D (2004) Impaired insulin sensitivity, insulin secretion, and glucose effectiveness predict future development of impaired glucose tolerance and type 2 diabetes in pre-diabetic African Americans: implications for primary diabetes prevention. Diabetes Care 27:1439–1446CrossRefGoogle Scholar
- 18.Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (2003) Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 26(Suppl 1):S5–S20Google Scholar
- 19.Hanefeld M, Koehler C, Fuecker K, Henkel E, Schaper F, Temelkova-Kurktschiev T (2003) Insulin secretion and insulin sensitivity pattern is different in isolated impaired glucose tolerance and impaired fasting glucose: the risk factor in impaired glucose tolerance for atherosclerosis and diabetes study. Diabetes Care 26:868–874CrossRefGoogle Scholar
- 22.Jia W, Chen L, Xiang K, Lu J, Bao Y, Xue F, Lu W (2001) Establishment of an extended hyperinsulinemic euglycemic clamp technique. Chin J Endocrinol Metab 17:268–271Google Scholar
- 23.Pacini G, Tonolo G, Sambataro M, Maioli M, Ciccarese M, Brocco E, Avogaro A, Nosadini R (1998) Insulin sensitivity and glucose effectiveness: minimal model analysis of regular and insulin-modified FSIGT. Am J Physiol 274:E592–E599Google Scholar
- 30.DeFronzo RA, Tobin JD, Andres R (1979) Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 237:E214–E223Google Scholar
- 38.Kurosu H, Choi M, Ogawa Y, Dickson AS, Goetz R, Eliseenkova AV, Mohammadi M, Rosenblatt KP, Kliewer SA, Kuro-o M (2007) Tissue-specific expression of betaKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21. J Biol Chem 282:26687–26695CrossRefGoogle Scholar