Insulin sensitization of human preadipocytes through glucocorticoid hormone induction of forkhead transcription factors.

Autor: Tomlinson JJ; Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada., Boudreau A, Wu D, Abdou Salem H, Carrigan A, Gagnon A, Mears AJ, Sorisky A, Atlas E, Haché RJ
Jazyk: angličtina
Zdroj: Molecular endocrinology (Baltimore, Md.) [Mol Endocrinol] 2010 Jan; Vol. 24 (1), pp. 104-13. Date of Electronic Publication: 2009 Nov 03.
DOI: 10.1210/me.2009-0091
Abstrakt: 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: MEDLINE