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Oxidative Medicine and Cellular Longevity
Volume 2017, Article ID 3035184, 13 pages
https://doi.org/10.1155/2017/3035184
Research Article

Insulin-Like Growth Factor (IGF) Binding Protein-2, Independently of IGF-1, Induces GLUT-4 Translocation and Glucose Uptake in 3T3-L1 Adipocytes

1Department of Endocrinology, Diabetes and Nutrition, Charité-University Medicine Berlin, Berlin, Germany
2Department of Endocrinology, Diabetes and Nutrition at the Center for Cardiovascular Research (CCR), Charité-University Medicine Berlin, Berlin, Germany
3Division of Physiology, Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt
4Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
5Section of Metabolic Vascular Medicine, Medical Clinic III, and Paul Langerhans Institute Dresden (PLID), Dresden University of Technology, Dresden, Germany
6Division of Diabetes & Nutritional Sciences, Faculty of Life Sciences & Medicine, King’s College London, London, UK
7Department of Endocrinology, Diabetes and Nutrition at the Experimental and Clinical Research Centre (ECRC), Charité-University Medicine Berlin and Max-Delbrück Center Berlin-Buch, Berlin, Germany

Correspondence should be addressed to Ayman M. Arafat; ed.etirahc@tafara.namya

Received 13 September 2017; Accepted 23 October 2017; Published 20 December 2017

Academic Editor: Mohamed M. Abdel-Daim

Copyright © 2017 Biruhalem Assefa et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Insulin-like growth factor binding protein-2 (IGFBP-2) is the predominant IGF binding protein produced during adipogenesis and is known to increase the insulin-stimulated glucose uptake (GU) in myotubes. We investigated the IGFBP-2-induced changes in basal and insulin-stimulated GU in adipocytes and the underlying mechanisms. We further determined the role of insulin and IGF-1 receptors in mediating the IGFBP-2 and the impact of IGFBP-2 on the IGF-1-induced GU. Fully differentiated 3T3-L1 adipocytes were treated with IGFBP-2 in the presence and absence of insulin and IGF-1. Insulin, IGF-1, and IGFBP-2 induced a dose-dependent increase in GU. IGFBP-2 increased the insulin-induced GU after long-term incubation. The IGFBP-2-induced impact on GU was neither affected by insulin or IGF-1 receptor blockage nor by insulin receptor knockdown. IGFBP-2 significantly increased the phosphorylation of PI3K, Akt, AMPK, TBC1D1, and PKCζ/λ and induced GLUT-4 translocation. Moreover, inhibition of PI3K and AMPK significantly reduced IGFBP-2-stimulated GU. In conclusion, IGFBP-2 stimulates GU in 3T3-L1 adipocytes through activation of PI3K/Akt, AMPK/TBC1D1, and PI3K/PKCζ/λ/GLUT-4 signaling. The stimulatory effect of IGFBP-2 on GU is independent of its binding to IGF-1 and is possibly not mediated through the insulin or IGF-1 receptor. This study highlights the potential role of IGFBP-2 in glucose metabolism.