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Journal of Pediatric Endocrinology and Metabolism

Editor-in-Chief: Kiess, Wieland

Ed. by Bereket, Abdullah / Darendeliler, Feyza / Dattani, Mehul / Gustafsson, Jan / Luo, Fei Hong / Mericq, Veronica / Toppari, Jorma

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Volume 30, Issue 5


Plasma but not serum brain-derived neurotrophic factor concentration is decreased by oral glucose tolerance test-induced hyperglycemia in children

Shunsuke Araki / Yukiyo Yamamoto / Reiko Saito / Aoi Kawakita / Mami Eguchi / Motohide Goto / Kazuyasu Kubo / Rinko Kawagoe / Yasusada Kawada / Koichi Kusuhara
Published Online: 2017-03-22 | DOI: https://doi.org/10.1515/jpem-2016-0344



Little is known regarding the relationships among circulating brain-derived neurotrophic factor (BDNF) levels and glucose or insulin in children and adolescents. The objective of this study was to investigate whether circulating BDNF levels would change during the oral glucose tolerance test (OGTT).


We performed the OGTT and measured the serial changes in BDNF levels in both plasma and serum.


There were 22 subjects in the normal type (N) group and 20 in the borderline/diabetic type (B/D) group, defined by the results of the OGTT. Serum levels of BDNF were almost five times higher and plasma levels gradually decreased during the OGTT, whereas serum levels showed no significant change. The reduction of plasma BDNF level changes from baseline to 120 min were significantly different between the N and B/D groups (36.3% vs. 20.8%, p=0.023).


Our results showed that plasma levels of BDNF are more sensitive to acute changes in glucose or insulin levels than serum.

Keywords: brain-derived neurotrophic factor; child and adolescents; glucose tolerance test; insulin; platelets


  • 1.

    Tapia-Arancibia L, Rage F, Givalois L, Arancibia S. Physiology of BDNF: focus on hypothalamic function. Front Neuroendocrinol 2004;25:77–107.CrossrefGoogle Scholar

  • 2.

    Mowla SJ, Farhadi HF, Pareek S, Atwal JK, Morris SJ, et al. Biosynthesis and post-translational processing of the precursor to brain-derived neurotrophic factor. J Biol Chem 2001;276:12660–6.Google Scholar

  • 3.

    Huang EJ, Reichardt LF. Trk receptors: roles in neuronal signal transduction. Annu Rev Biochem 2003;72:609–42.Google Scholar

  • 4.

    Lyons WE, Mamounas LA, Ricaurte GA, Coppola V, Reid SW, et al. Brain-derived neurotrophic factor-deficient mice develop aggressiveness and hyperphagia in conjunction with brain serotonergic abnormalities. Proc Natl Acad Sci USA 1999;96:15239–44.Google Scholar

  • 5.

    Chaldakov GN, Fiore M, Stankulov IS, Hristova M, Antonelli A, et al. NGF, BDNF, leptin, and mast cells in human coronary atherosclerosis and metabolic syndrome. Arch Physiol Biochem 2001;109:357–60.Google Scholar

  • 6.

    Hristova M, Aloe L. Metabolic syndrome – neurotrophic hypothesis. Med Hypotheses 2006;66:545–9.Web of ScienceGoogle Scholar

  • 7.

    El-Gharbawy AH, Adler-Wailes DC, Mirch MC, Theim KR, Ranzenhofer L, et al. Serum brain-derived neurotrophic factor concentrations in lean and overweight children and adolescents. J Clin Endocrinol Metab 2006;91:3548–52.Google Scholar

  • 8.

    Bullo M, Peeraully MR, Trayhurn P, Folch J, Salas-Salvado J. Circulating nerve growth factor levels in relation to obesity and the metabolic syndrome in women. Eur J Endocrinol 2007;157:303–10.Web of ScienceGoogle Scholar

  • 9.

    Araki S, Yamamoto Y, Dobashi K, Asayama K, Kusuhara K. Decreased plasma levels of brain-derived neurotrophic factor and its relationship with obesity and birth weight in obese Japanese children. Obes Res Clin Pract 2014;8:e63–9.CrossrefWeb of ScienceGoogle Scholar

  • 10.

    Nakagawa T, Tsuchida A, Itakura Y, Nonomura T, Ono M, et al. Brain-derived neurotrophic factor regulates glucose metabolism by modulating energy balance in diabetic mice. Diabetes 2000;49:436–44.CrossrefGoogle Scholar

  • 11.

    Pelleymounter MA, Cullen MJ, Wellman CL. Characteristics of BDNF-induced weight loss. Exp Neurol 1995;131:229–38.Google Scholar

  • 12.

    Donovan MJ, Miranda RC, Kraemer R, McCaffrey TA, Tessarollo L, et al. Neurotrophin and neurotrophin receptors in vascular smooth muscle cells. Regulation of expression in response to injury. Am J Pathol 1995;147:309–24.Google Scholar

  • 13.

    Nakahashi T, Fujimura H, Altar CA, Li J, Kambayashi J, et al. Vascular endothelial cells synthesize and secrete brain-derived neurotrophic factor. FEBS Lett 2000;470:113–7.Google Scholar

  • 14.

    Pan W, Banks WA, Fasold MB, Bluth J, Kastin AJ. Transport of brain-derived neurotrophic factor across the blood-brain barrier. Neuropharmacology 1998;37:1553–61.Google Scholar

  • 15.

    Fujimura H, Altar CA, Chen R, Nakamura T, Nakahashi T, et al. Brain-derived neurotrophic factor is stored in human platelets and released by agonist stimulation. Thromb Haemost 2002;87:728–34.Google Scholar

  • 16.

    Karczewska-Kupczewska M, Straczkowski M, Adamska A, Nikolajuk A, Otziomek E, et al. Decreased serum brain-derived neurotrophic factor concentration in young nonobese subjects with low insulin sensitivity. Clin Biochem 2011;44:817–20.CrossrefWeb of ScienceGoogle Scholar

  • 17.

    Tonoli C, Heyman E, Roelands B, Buyse L, Piacentini F, et al. BDNF, IGF-I, glucose and insulin during continuous and interval exercise in type 1 diabetes. Int J Sports Med 2015;36:955–9.Web of ScienceGoogle Scholar

  • 18.

    Krabbe KS, Nielsen AR, Krogh-Madsen R, Plomgaard P, Rasmussen P, et al. Brain-derived neurotrophic factor (BDNF) and type 2 diabetes. Diabetologia 2007;50:431–8.Web of ScienceCrossrefGoogle Scholar

  • 19.

    Sahin NM, Kinik ST, Tekindal MA. OGTT results in obese adolescents with normal HOMA-IR values. J Pediatr Endocrinol Metab 2013;26:285–91.Web of ScienceCrossrefGoogle Scholar

  • 20.

    Committee of the Japan Diabetes Society on the Diagnostic Criteria of Diabetes Mellitus, Seino Y, Nanjo K, Tajima N, Kadowaki T, et al. Report of the committee on the classification and diagnostic criteria of diabetes mellitus. J Diabetes Investig 2010;1: 212–28.CrossrefGoogle Scholar

  • 21.

    Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412–9.CrossrefGoogle Scholar

  • 22.

    Lommatzsch M, Zingler D, Schuhbaeck K, Schloetcke K, Zingler C, et al. The impact of age, weight and gender on BDNF levels in human platelets and plasma. Neurobiol Aging 2005;26:115–23.CrossrefGoogle Scholar

  • 23.

    Iughetti L, Casarosa E, Predieri B, Patianna V, Luisi S. Plasma brain-derived neurotrophic factor concentrations in children and adolescents. Neuropeptides 2011;45:205–11.Web of ScienceCrossrefGoogle Scholar

  • 24.

    Karczewska-Kupczewska M, Kowalska I, Nikolajuk A, Adamska A, Zielinska M, et al. Circulating brain-derived neurotrophic factor concentration is downregulated by intralipid/heparin infusion or high-fat meal in young healthy male subjects. Diabetes Care 2012;35:358–62.Web of ScienceCrossrefGoogle Scholar

  • 25.

    Kishino A, Katayama N, Ishige Y, Yamamoto Y, Ogo H, et al. Analysis of effects and pharmacokinetics of subcutaneously administered BDNF. Neuroreport 2001;12:1067–72.CrossrefGoogle Scholar

  • 26.

    Kiess W, Gorski T, Penke M, Klamt S, Kapellen TM. Diabetes mellitus in children and adolescents – a global epidemic which has become neglected. J Pediatr Endocrinol Metab 2015;28:247–50.Web of ScienceGoogle Scholar

About the article

Corresponding author: Shunsuke Araki, MD, PhD, Department of Pediatrics, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan, Phone: +81 (93) 691-7254, Fax: +81 (93) 691-9338

Received: 2016-08-31

Accepted: 2017-02-02

Published Online: 2017-03-22

Published in Print: 2017-05-01

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: This work was supported by a Grant-in-Aid for Scientific Research #25860893 (to S.A.) and #21591340 (to Y.Y.) from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Citation Information: Journal of Pediatric Endocrinology and Metabolism, Volume 30, Issue 5, Pages 525–530, ISSN (Online) 2191-0251, ISSN (Print) 0334-018X, DOI: https://doi.org/10.1515/jpem-2016-0344.

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