FOXO1 content is reduced in cystic fibrosis and increases with IGF-I treatment

Arianna Smerieri, Luisa Montanini, Luigi Maiuri, Sergio Bernasconi, Maria E. Street

Research output: Contribution to journalArticlepeer-review


Cystic fibrosis-related diabetes is to date the most frequent complication in cystic fibrosis (CF). The mechanisms underlying this condition are not well understood, and a possible role of insulin resistance is debated. We investigated insulin signal transduction in CF. Total insulin receptor, IRS1, p85 PI3K, and AKT contents were substantially normal in CF cells (CFBE41o-), whereas winged helix forkhead (FOX)O1 contents were reduced both in baseline conditions and after insulin stimulation. In addition, CF cells showed increased ERK1/2, and reduced β2 arrestin contents. No significant change in SOCS2 was observed. By using a CFTR inhibitor and siRNA, changes in FOXO1 were related to CFTR loss of function. In a CF-affected mouse model, FOXO1 content was reduced in the muscle while no significant difference was observed in liver and adipose tissue compared with wild-type. Insulin-like growth factor 1 (IGF-I) increased FOXO1 content in vitro and in vivo in muscle and adipose tissue. In conclusion; we present the first description of reduced FOXO1 content in CF, which is compatible with reduced gluconeogenesis and increased adipogenesis, both features of insulin insensitivity. IGF-I treatment was effective in increasing FOXO1, thereby suggesting that it could be considered as a potential treatment in CF patients possibly to prevent and treat cystic fibrosis-related diabetes.

Original languageEnglish
Pages (from-to)18000-18022
Number of pages23
JournalInternational Journal of Molecular Sciences
Issue number10
Publication statusPublished - Oct 8 2014


  • AKT
  • Cystic fibrosis-related diabetes
  • ERK1 and 2
  • FOXO1
  • IGF-I
  • Insulin
  • Insulin resistance
  • IRS1
  • SOCS2
  • β2 arrestin

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Spectroscopy
  • Inorganic Chemistry
  • Catalysis
  • Molecular Biology
  • Computer Science Applications
  • Medicine(all)


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