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.