Insulin resistance is associated with increased serum concentration of IGF-binding protein-related protein 1 (IGFBP-rP1/MAC25)

Abel López-Bermejo, Javad Khosravi, José Manuel Fernández-Real, Vivian Hwa, Katherine L. Pratt, Roser Casamitjana, Maria M. Garcia-Gil, Ron G. Rosenfeld, Wifredo Ricart

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37 Scopus citations

Abstract

IGF-binding protein (IGFBP)-related protein 1 (IGFBP-rP1) has been shown to bind both IGFs and insulin, albeit with low affinity, and to inhibit insulin signaling. We hypothesized that IGFBP-rP1 is associated with insulin resistance and components of the IGF system in humans. To this aim, a cross-sectional study was conducted in 113 nondiabetic and 43 type 2 diabetic men. Insulin sensitivity (insulin sensitivity index [Si] from intravenous glucose tolerance tests in nondiabetic subjects, or the rate constant for disappearance of glucose [KITT] from insulin tolerance tests in type 2 diabetic subjects), circulating IGFBP-rP1 (from enzyme-linked immunosorbent assay), adiponectin (from radioimmunoassay), C-reactive protein (CRP; from immunoturbidimetry), soluble tumor necrosis factor receptor 2 (sTNFR2; from enzyme-amplified sensitivity immunoassay), and IGF system parameters (IGF-I, free IGF-I, and IGFBP-1 from immunoradiometric assay) were assessed in all subjects. Among nondiabetic men, those in the highest quartile for circulating IGFBP-rP1 exhibited decreased Si and adiponectin (both P < 0.01) as well as increased CRP and sTNFR2 (both P < 0.05). Circulating IGFBP-rP1 was also found to be increased in previously undiagnosed type 2 diabetic patients (P = 0.01) but not in known type 2 diabetic patients receiving pharmacological therapy. Although no changes in IGF system components were evident by IGFBP-rP1 quartiles in nondiabetic subjects, independent positive associations of IGFBP-rP1 with circulating fasting IGFBP-1 were evident after adjustment for insulin resistance parameters in both nondiabetic and type 2 diabetic subjects, with IGFBP-rP1 explaining 2 and 11% of IGFBP-1 variance, respectively. In additional multivariate analyses, Si, sTNFR2, and age stood as independent predictive variables of IGFBP-rP1 (together explaining 18% of its variance) in nondiabetic subjects, and BMI became the only independent predictive variable of IGFBP-rP1 (explaining 26% of its variance) in type 2 diabetic men. These findings show for the first time that circulating IGFBP-rP1 is increased with insulin resistance, and they also suggest novel interactions between IGFBP-rP1 and the IGF system in humans.

Original languageEnglish (US)
Pages (from-to)2333-2339
Number of pages7
JournalDiabetes
Volume55
Issue number8
DOIs
StatePublished - Aug 1 2006

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Keywords

  • CRP, C-reactive protein
  • IGFBP, IGF-binding protein
  • IGFBP-rP, IGFBP-related protein
  • TNF, tumor necrosis factor
  • sTNFR, soluble tumor necrosis factor receptor

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

López-Bermejo, A., Khosravi, J., Fernández-Real, J. M., Hwa, V., Pratt, K. L., Casamitjana, R., Garcia-Gil, M. M., Rosenfeld, R. G., & Ricart, W. (2006). Insulin resistance is associated with increased serum concentration of IGF-binding protein-related protein 1 (IGFBP-rP1/MAC25). Diabetes, 55(8), 2333-2339. https://doi.org/10.2337/db05-1627