Insulin Sensitization of Human Preadipocytes through Glucocorticoid Hormone Induction of Forkhead Transcription Factors
| Autor: | Dongmei Wu, Alan J. Mears, Alexander Sorisky, Houssein Abdou Salem, Adèle Boudreau, Ella Atlas, Julianna J. Tomlinson, AnneMarie Gagnon, Robert J. G. Haché, Amanda Carrigan |
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| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_specialty
Time Factors medicine.medical_treatment Adipose tissue Mice Phosphatidylinositol 3-Kinases Endocrinology 3T3-L1 Cells Internal medicine Insulin receptor substrate Adipocytes medicine Animals Humans Insulin Glucocorticoids Molecular Biology Protein kinase B Cells Cultured Oligonucleotide Array Sequence Analysis Original Research Adipogenesis Dose-Response Relationship Drug biology Gene Expression Profiling Forkhead Transcription Factors General Medicine Receptor Insulin IRS2 IRS1 Insulin receptor Gene Expression Regulation Insulin Receptor Substrate Proteins biology.protein Female Proto-Oncogene Proteins c-akt |
| Zdroj: | Molecular Endocrinology. 24:104-113 |
| ISSN: | 1944-9917 0888-8809 |
| Popis: | Glucocorticoids are synthesized locally in adipose tissue and contribute to metabolic disease through the facilitation of adipose tissue expansion. Here we report that exposure of human primary preadipocytes to glucocorticoids increases their sensitivity to insulin and enhances their subsequent response to stimuli that promote differentiation. This effect was observed in primary human preadipocytes but not in immortalized 3T3-L1 murine preadipocytes or in fully differentiated primary human adipocytes. Stimulation of insulin signaling was mediated through induction of insulin receptor (IR), IR substrate protein 1 (IRS1), IRS2, and the p85 regulatory subunit of phosphoinositide-3-3-kinase, which led to enhanced insulin-mediated activation of Akt. Although induction of IRS2 was direct, induction of IR and IRS1 by glucocorticoids occurred subsequent to primary induction of the forkhead family transcription factors FoxO1A and FoxO3A. These results reveal a new role for glucocorticoids in preparing preadipocytes for differentiation. |
| Databáze: | OpenAIRE |
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