Circulating FGF-21 Levels in Normal Subjects and in Newly Diagnose Patients with Type 2 Diabetes Mellitus

Abstract

Fibroplast growth factor (FGF-21) is a recently discovered metabolic regulator. Its pathophysiologic role in humans remains unknown. In this study, we have investigated whether or not plasma FGF-21 level was different in patients with type 2 diabetes mellitus (T2DM) and non-diabetic controls. We also assessed associations between plasma FGF-21 body composition and several metabolic parameters. Fasting FGF-21 levels were significantly increased in patients with T2DM compared with controls (1.82±0.65 vs. 1.53±0.60 μg/L, P<0.05). In T2DM patients, fasting plasma FGF-21 correlate negatively with fasting blood glucose (r=-0.31, P<0.05). Multiple regression analysis showed that FBG, plasma insulin and HOMA_IS were independent influencing plasma FGF-21 levels. The present work suggests a potential role for FGF-21 in the pathogenesis of insulin resistance and T2DM.

Key words

FGF-21 - insulin resistance - T2DM

References

• 1 Sakaue H, Konishi M, Ogawa W, Asaki T, Mori T, Yamasaki M, Takata M, Ueno H, Kato S, Kasuga M, Itoh N. Requirement of fibroblast growth factor 10 in development of white adipose tissue.  Genes Dev. 2002;  16 908-912
• 2 Bhushan A, Itoh N, Kato S, Thiery JP, Czernichow P, Bellusci S, Scharfmann R. FGF10 is essential for maintaining the proliferative capacity of epithelial progenitor cells during early pancreatic organogenesis.  Development. 2001;  128 5109-5117
• 3 Ohuchi H, Hori Y, Yamasaki M, Harada H, Sekine K, Kato S, Itoh N. FGF10 acts as a major ligand for FGF receptor 2 IIIb in mouse multi-organ development.  Biochem Biophys Res Commun. 2000;  277 643-649
• 4 Konishi M, Micami T, Yamasaki M, Miyake A, Itoh N. Fibroblast growth factor-16 is a growth factor for embryonic brown adipocytes.  J Biol Chem. 1999;  255 12119-12122
• 5 Nishimura T, Utsonomiya Y, Hoshikawa M, Ohuchi H, Itoh N. Structure and expression of a novel human FGF, FGF-19, expressed in the fetal brain.  Biochim Biophys Acta. 1999;  1444 148-151
• 6 Xie MH, Holcomb I, Deuel B, Dowd P, Huang A, Vagts A, Foster J, Liang J, Brush J, Gu Q, Hillan K, Goddard A, Gurney AL. FGF-19, a novel fibroblast growth factor with unique specificity for FGFR4.  Cytokine. 1999;  11 729-735
• 7 Tomlinson E, Fu L, John L, Hultgren B, Huang X, Renz M, Stephan JP, Tsai SP, Powell-Braxton L, French D, Stewart TA. Transgenic mice expressing human fibroblast growth factor-19 display increased metabolic rate and decreased adiposity.  Endocrinology. 2002;  143 1741-1747
• 8 Fu L, John LM, Adams SH, Yu XX, Tomlinson E, Renz M, Williams PM, Soriano R, Corpuz R, Moffat B, Vandlen R, Simmons L, Foster J, Stephan JP, Tsai SP, Stewart TA. Fibroblast growth factor 19 increases metabolic rate and reverses dietary and leptin deficient diabetes.  Endocrinology. 2004;  145 2594-2603
• 9 Nishimura T, Nakatake Y, Konishi M, Itoh N. Identification of a novel FGF, FGF-21, preferentially expressed in the liver.  Biochim Biophys Acta. 2000;  1492 203-206
• 10 Kharitonenkov A, Shiyanova TL, Koester A, Ford AM, Micanovic R, Galbreath EJ, Sandusky GE, Hammond LJ, Moyers JS, Owens RA, Gromada J, Brozinick JT, Hawkins ED, Wroblewski VJ, Li DS, Mehrbod F, Jaskunas SR, Shanafelt AB. FGF-21 as a novel metabolic regulator.  J Clin Invest. 2005;  115 1627-1635
• 11 Knebel B, Avci H, Bullmann C, Kotzka J, Müller-Wieland D. Reduced phosphorylation of transcription factor Elk-1 in cultured fibroblasts of a patient with premature aging syndrome and insulin resistance.  Exp Clin Endocrinol Diabetes. 2005;  113 94-101
• 12 Wente W, Efanov AM, Brenner M, Kharitonenkov M, Köster A, Sandusky GE, Sewing S, Treinies I, Zitzer H, Gromada J. Fibroblast growth factor-21 improves pancreatic ß-cell function and survival by activation of extracellular signal-regulated kinase 1/2 and Akt signaling pathways.  Diabetes. 2006;  55 2470-2478
• 13 Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. 1. Diagnosis and classification of diabetes mellitus, provisional report of a WHO consultation.  Diabetes Medicine. 1998;  15 539-553
• 14 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.  Diabetologia. 1985;  28 412-419

Correspondence