CONTEXT: Transgenic mice overexpressing IGF binding protein-3 (IGFBP-3) have insulin resistance with reduced uptake of 2-deoxyglucose in muscle and adipose tissue. OBJECTIVE: Our aim was to investigate the effects of IGFBP-3 on glucose uptake in adipocytes. RESULTS: In 3T3-L1 adipocytes, IGFBP-3 reduced insulin-stimulated but not basal glucose uptake. This was independent of IGF binding because IGFBP-2 and IGFBP-1 had no effect, whereas two non-IGF binding mutants of IGFBP-3 were inhibitory. The effect of IGFBP-3 was independent of the blockade of the IGF-I receptor. A mutant form of IGFBP-3 that does not translocate to the nucleus or bind retinoid X receptor-alpha was able to inhibit insulin-stimulated glucose uptake, indicating that nuclear translocation and retinoid X receptor-alpha binding are not essential for this IGFBP-3 action. IGFBP-3 reduced insulin-stimulated glucose transporter-4 translocation to the plasma membrane and reduced threonine phosphorylation of Akt. Collectively, our data indicate that IGFBP-3 impacts on the insulin signaling pathway to inhibit insulin-stimulated glucose uptake independent of IGFs and through nonnuclear mechanisms. Finally, we showed that IGFBP-3 inhibited insulin-stimulated glucose uptake in omental but not s.c. adipose tissue explants. CONCLUSION: IGFBP-3 may contribute to insulin resistance in adipocytes.
CONTEXT: Transgenic mice overexpressing IGF binding protein-3 (IGFBP-3) have insulin resistance with reduced uptake of 2-deoxyglucose in muscle and adipose tissue. OBJECTIVE: Our aim was to investigate the effects of IGFBP-3 on glucose uptake in adipocytes. RESULTS: In 3T3-L1 adipocytes, IGFBP-3 reduced insulin-stimulated but not basal glucose uptake. This was independent of IGF binding because IGFBP-2 and IGFBP-1 had no effect, whereas two non-IGF binding mutants of IGFBP-3 were inhibitory. The effect of IGFBP-3 was independent of the blockade of the IGF-I receptor. A mutant form of IGFBP-3 that does not translocate to the nucleus or bind retinoid X receptor-alpha was able to inhibit insulin-stimulated glucose uptake, indicating that nuclear translocation and retinoid X receptor-alpha binding are not essential for this IGFBP-3 action. IGFBP-3 reduced insulin-stimulated glucose transporter-4 translocation to the plasma membrane and reduced threonine phosphorylation of Akt. Collectively, our data indicate that IGFBP-3 impacts on the insulin signaling pathway to inhibit insulin-stimulated glucose uptake independent of IGFs and through nonnuclear mechanisms. Finally, we showed that IGFBP-3 inhibited insulin-stimulated glucose uptake in omental but not s.c. adipose tissue explants. CONCLUSION:IGFBP-3 may contribute to insulin resistance in adipocytes.
Authors: Samer Gawrieh; Tesfaye M Baye; Melanie Carless; James Wallace; Richard Komorowski; David E Kleiner; Deborah Andris; Bassem Makladi; Regina Cole; Michael Charlton; Joanne Curran; Thomas D Dyer; Jac Charlesworth; Russell Wilke; John Blangero; Ahmed H Kissebah; Michael Olivier Journal: Obes Surg Date: 2010-12 Impact factor: 4.129
Authors: Qianning Jiao; Anne M Pruznak; Danuta Huber; Thomas C Vary; Charles H Lang Journal: Am J Physiol Endocrinol Metab Date: 2009-09-15 Impact factor: 4.310
Authors: Carrie M Elks; Peng Zhao; Ryan W Grant; Hardy Hang; Jennifer L Bailey; David H Burk; Margaret A McNulty; Randall L Mynatt; Jacqueline M Stephens Journal: J Biol Chem Date: 2016-06-20 Impact factor: 5.157