Insulin-like growth factor binding protein-3 induces insulin resistance in adipocytes in vitro and in rats in vivo

Hae Soon Kim, Omar Ali, Melanie Shim, Kuk Wha Lee, Patricia Vuguin, Radhika Muzumdar, Nir Barzilai, Pinchas Cohen

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Insulin-like growth factor binding protein (IGFBP)-3 binds to IGF and modulates their actions and also possesses intrinsic activities. We investigated its effects on insulin action and found that when IGFBP-3 was added to fully differentiated 3T3-L1 adipocytes in culture, insulin-stimulated glucose transport was significantly inhibited to 60% of control in a time- and dose-dependent manner. Tumor necrosis factor (TNF)-α treatment also inhibited glucose transport to the same degree as IGFBP-3 and, in addition, increased IGFBP-3 levels 3-fold. Co-treatment with TNF-α and IGFBP-3 antisense partially prevented the inhibitory effect of TNF-α on glucose transport, indicating a role for IGFBP-3 in cytokine-induced insulin resistance. Insulin-stimulated phosphorylation of the insulin receptor was markedly decreased by IGFBP-3 treatment. IGFBP-3 treatment suppressed adiponectin expression in 3T3-L1 adipocytes. Infusion of IGFBP-3 to Sprague-Dawley rats for 3 h decreased peripheral glucose uptake by 15% compared with controls as well as inhibiting glycogen synthesis. Systemic administration of IGFBP-3 to rats for 7 d resulted in a dramatic 40% decrease in peripheral glucose utilization and glycogen synthesis. These in vitro and in vivo findings demonstrate that IGFBP-3 has potent insulin-antagonizing capability and suggest a role for IGFBP-3 in cytokine-induced insulin resistance and other mechanisms involved in the development of type-2 diabetes.

Original languageEnglish (US)
Pages (from-to)159-164
Number of pages6
JournalPediatric Research
Volume61
Issue number2
DOIs
StatePublished - Feb 2007

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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