FOXO1 Content Is Reduced in Cystic Fibrosis and Increases with IGF-I Treatment
| العنوان: | FOXO1 Content Is Reduced in Cystic Fibrosis and Increases with IGF-I Treatment |
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| المؤلفون: | Maria E. Street, Sergio Bernasconi, Luisa Montanini, Luigi Maiuri, Arianna Smerieri |
| المصدر: | International Journal of Molecular Sciences, Vol 15, Iss 10, Pp 18000-18022 (2014) International Journal of Molecular Sciences Volume 15 Issue 10 Pages 18000-18022 |
| بيانات النشر: | MDPI AG, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Cystic Fibrosis, IRS1, medicine.medical_treatment, Cystic Fibrosis Transmembrane Conductance Regulator, Adipose tissue, Suppressor of Cytokine Signaling Proteins, FOXO1, lcsh:Chemistry, Mice, Phosphatidylinositol 3-Kinases, insulin resistance, SOCS2, Insulin-Like Growth Factor I, Phosphorylation, lcsh:QH301-705.5, Spectroscopy, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Forkhead Box Protein O1, ERK1 and 2, Forkhead Transcription Factors, General Medicine, Recombinant Proteins, Cystic fibrosis transmembrane conductance regulator, Computer Science Applications, IGF-I, Adipose Tissue, Female, Signal Transduction, β2 arrestin, medicine.medical_specialty, insulin, Cystic fibrosis-related diabetes, cystic fibrosis-related diabetes, Biology, Article, Catalysis, Cell Line, Inorganic Chemistry, Insulin resistance, Internal medicine, medicine, Animals, Mice, Inbred CFTR, Physical and Theoretical Chemistry, Muscle, Skeletal, Molecular Biology, Insulin, AKT, Organic Chemistry, medicine.disease, Insulin receptor, Endocrinology, lcsh:Biology (General), lcsh:QD1-999, Insulin Receptor Substrate Proteins, biology.protein, Proto-Oncogene Proteins c-akt |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1422-0067 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::389b5b3aaa82d911c91edf17750fe806Test http://www.mdpi.com/1422-0067/15/10/18000Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....389b5b3aaa82d911c91edf17750fe806 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14220067 |
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