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. 2011 Jun 20;60(7):1872–1881. doi: 10.2337/db11-0248

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© 2011 by the American Diabetes Association.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

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FIG. 8. — Suppression of FoxO1 by insulin and insulin-mimetics. Suppression of FoxO1 by insulin or Mαα-activated AMPK may be ascribed to its nuclear exclusion and degradation, complemented by suppression of its nuclear transcriptional activity by insulin- or Mαα-induced C/EBPβ isoforms. In contrast with insulin and Mαα, suppression of FoxO1 by metformin is solely accounted for by nuclear exclusion of FoxO1 by metformin-activated AMPK. Suppression of transactivation in the context of FRE-responsive promoters may account for the insulin-sensitizing activity and hypoglycemic hypolipidemic efficacy, whereas suppression of FoxO1 coactivation of STAT3-responsive promoters may account for the insulin-sensitizing activity, anti-inflammatory, and antiatherogenic efficacy of insulin and insulin sensitizers.