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Publication
Glucose Transporter-4 Facilitates Insulin-Stimulated Glucose Uptake in
Osteoblasts.
Authors Li Z, Frey JL, Wong GW, Faugere MC, Wolfgang MJ, Kim JK, Riddle RC, Clemens TL
Submitted By Submitted Externally on 11/30/2016
Status Published
Journal Endocrinology
Year 2016
Date Published
Volume : Pages 157 : 4094 - 4103
PubMed Reference 27689415
Abstract Recent studies have identified the osteoblast as an insulin responsive cell that
participates in global energy homeostasis. Here, we show that glucose
transporter-4 (Glut4) is required for insulin-dependent uptake and oxidation of
glucose in mature osteoblasts. In primary cultures of mouse osteoblasts, insulin
increased uptake and oxidation of (14)C-glucose in a dose-dependent fashion but
did not significantly affect uptake or oxidation of (14)C-oleate. In vitro,
undifferentiated osteoblasts expressed 3 high-affinity Gluts: Glut1, Glut4, and
Glut3. However, although levels of Glut1 and Glut3 remained constant during the
course of osteoblast differentiation, Glut4 expression increased by 5-fold in
association with enhanced insulin-stimulated glucose uptake. Glut4 ablation in
osteoblasts in vitro eliminated insulin-stimulated glucose uptake, reduced
proliferation and diminished measures of osteoblast maturation. In vivo, Glut4
expression was observed in osteoblasts, osteocytes, and chondrocytes at a level
approaching that observed in adjacent skeletal muscle. To determine the
importance of Glut4 in bone in vivo, we generated mice lacking Glut4 in
osteoblasts and osteocytes (?Glut4). ?Glut4 mice exhibited normal bone
architecture but exhibited an increase in peripheral fat in association with
hyperinsulinemia, ß-cell islet hypertrophy, and reduced insulin sensitivity.
Surprisingly, the expression of insulin target genes in liver, muscle, and
adipose from ?Glut4 mice were unchanged or increased, indicating that
alterations in glucose homeostasis were the result of reduced clearance by bone.
These findings suggest that Glut4 mediates insulin-stimulated glucose uptake by
mature osteoblasts/osteocytes and that the magnitude of glucose use by bone
cells is sufficient to impact global glucose disposal in the mouse.






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