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J Clin Endocrinol Metab. 2005 Dec;90(12):6588-95. Epub 2005 Sep 27.

Insulin-like growth factor binding protein-3 leads to insulin resistance in adipocytes.

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Kolling Institute of Medical Research, Royal North Shore Hospital, Pacific Highway, St. Leonards 2065, NSW, Australia.



Transgenic mice overexpressing IGF binding protein-3 (IGFBP-3) have insulin resistance with reduced uptake of 2-deoxyglucose in muscle and adipose tissue.


Our aim was to investigate the effects of IGFBP-3 on glucose uptake in adipocytes.


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.


IGFBP-3 may contribute to insulin resistance in adipocytes.

[Indexed for MEDLINE]

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