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

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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

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Insulin-Like Growth Factor Binding Protein 3
Adipocytes
Insulin Resistance
Glucose
Insulin
Tumor Necrosis Factor-alpha
Glycogen
In Vitro Techniques
Cytokines
Adiponectin
Insulin Receptor
Type 2 Diabetes Mellitus
Sprague Dawley Rats

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Insulin-like growth factor binding protein-3 induces insulin resistance in adipocytes in vitro and in rats in vivo. / Kim, Hae Soon; Ali, Omar; Shim, Melanie; Lee, Kuk Wha; Vuguin, Patricia; Muzumdar, Radhika; Barzilai, Nir; Cohen, Pinchas.

In: Pediatric Research, Vol. 61, No. 2, 02.2007, p. 159-164.

Research output: Contribution to journalArticle

Kim, Hae Soon ; Ali, Omar ; Shim, Melanie ; Lee, Kuk Wha ; Vuguin, Patricia ; Muzumdar, Radhika ; Barzilai, Nir ; Cohen, Pinchas. / Insulin-like growth factor binding protein-3 induces insulin resistance in adipocytes in vitro and in rats in vivo. In: Pediatric Research. 2007 ; Vol. 61, No. 2. pp. 159-164.
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