| GLUT4 in murine bone growth: from uptake and translocation to proliferation and differentiation. | |
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MedLine Citation:
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PMID: 20923959 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Skeletal growth, taking place in the cartilaginous growth plates of long bones, consumes high levels of glucose for both metabolic and anabolic purposes. We previously showed that Glut4 is present in growing bone and is decreased in diabetes. In the present study, we examined the hypothesis that in bone, GLUT4 gene expression and function are regulated via the IGF-I receptor (IGF-IR) and that Glut4 plays an important role in bone growth. Insulin and IGF-I actions on skeletal growth and glucose uptake were determined using mandibular condyle (MC) organ cultures and MC-derived primary cell cultures (MCDC). Chondrogenesis was determined by following proliferation and differentiation activities using immunohistochemical (IHC) analysis of proliferating cell nuclear antigen and type II collagen expression, respectively. Overall condylar growth was assessed morphometrically. GLUT4 mRNA and protein levels were determined using in situ hybridization and IHC, respectively. Glut4 translocation to the cell membrane was assessed using confocal microscopy analysis of GFP-Glut4 fusion-transfected cells and immunogold and electron microscopy on MC sections; glucose uptake was assayed by 2-deoxyglucose (2-DOG) uptake. Both IGF-I and insulin-stimulated glucose uptake in MCDC, with IGF-I being tenfold more potent than insulin. Blockage of IGF-IR abrogated both IGF-I- and insulin-induced chondrogenesis and glucose metabolism. IGF-I, but not insulin, induced Glut4 translocation to the plasma membrane. Additionally, insulin induced both GLUT4 and IGF-IR gene expression and improved condylar growth in insulin receptor knockout mice-derived MC. Moreover, silencing of GLUT4 gene in MCDC culture abolished both IGF-I-induced glucose uptake and chondrocytic proliferation and differentiation. In growing bone, the IGF-IR pathway stimulates Glut4 translocation and enhances glucose uptake. Moreover, intact Glut4 cellular levels and translocation machinery are essential for early skeletal growth. |
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Authors:
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Gila Maor; Gaia Vasiliver-Shamis; Roni Hazan-Brill; Efrat Wertheimer; Eddy Karnieli |
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Publication Detail:
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Type: Journal Article Date: 2010-10-05 |
Journal Detail:
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Title: American journal of physiology. Endocrinology and metabolism Volume: 300 ISSN: 1522-1555 ISO Abbreviation: Am. J. Physiol. Endocrinol. Metab. Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-03-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901226 Medline TA: Am J Physiol Endocrinol Metab Country: United States |
Other Details:
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Languages: eng Pagination: E613-23 Citation Subset: IM |
Affiliation:
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Institute of Endocrinology, Diabetes and Metabolism, Rambam Medical Center and Rappaport Faculty of Medicine, Technion 12 Ha'alya St., Samy Ofer Tower., Floor 8, PO Box 9602, Haifa 31096, Israel. eddy@tx.technion.ac.il. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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