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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. and Mahmoud, A.M. and Pfeiffer, A.F.H. and Birkenfeld, A.L. and 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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