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Insulin-like growth factor (IGF) binding protein-2, independently of IGF-1, induces GLUT-4 translocation and glucose uptake in 3T3-L1 adipocytes

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Item Type:Article
Title:Insulin-like growth factor (IGF) binding protein-2, independently of IGF-1, induces GLUT-4 translocation and glucose uptake in 3T3-L1 adipocytes
Creators Name:Assefa, B., Mahmoud, A.M., Pfeiffer, A.F.H., Birkenfeld, A.L., Spranger, J. and Arafat, A.M.
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.
Keywords:3T3-L1 Cells, Adipocytes, Glucose, Glucose Transporter Type 4, Insulin, Insulin-Like Growth Factor Binding Protein 2, Insulin-Like Growth Factor I, Transfection, Animals, Mice
Source:Oxidative Medicine and Cellular Longevity
ISSN:1942-0900
Publisher:Hindawi
Volume:2017
Page Range:3035184
Date:20 December 2017
Official Publication:https://doi.org/10.1155/2017/3035184
PubMed:View item in PubMed

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