@entity1522 have emerged as potent modulators of the @entity3470 /p70 S6 kinase pathway. The involvement of this pathway in the regulation of insulin-stimulated @entity413 transport was investigated in the present study. Acute exposure (1 h) to a balanced mixture of @entity1522 reduced insulin-stimulated @entity413 transport by as much as 55% in L6 muscle cells. The effect of @entity1522 was fully prevented by the specific @entity3470 inhibitor @entity3446 . Time course analysis of @entity10175 ( @entity10175 )-associated @entity4357 (PI) 3-kinase activity revealed that incubation with @entity1522 speeds up its time-dependent deactivation, leading to a dramatic suppression (-70%) of its activity after 30 min of insulin stimulation as compared with its maximal activation (5 min of stimulation). This accelerated deactivation of PI 3-kinase activity in @entity535 -treated cells was associated with a concomitant and sustained increase in the phosphorylation of p70 S6 kinase. In marked contrast, inhibition of @entity3470 by @entity3446 maintained PI 3-kinase maximally activated for up to 30 min. The marked inhibition of insulin-mediated PI 3-kinase activity by @entity1522 was linked to a @entity3446 -sensitive increase in @entity563 / @entity1889 phosphorylation of @entity10175 and a decreased binding of the p85 subunit of PI 3-kinase to @entity10175 . Furthermore, @entity1522 were required for the degradation of @entity10175 during long term insulin treatment. These results identify the @entity3470 /p70 S6 kinase signaling pathway as a novel modulator of insulin-stimulated @entity413 transport in skeletal muscle cells.

XXXX and insulin signaling via the @entity3470 /p70 S6 kinase pathway. A negative feedback mechanism leading to insulin resistance in skeletal muscle cells.

@entity1522 :: ('CHEBI:33709', 'Chemical') :: ['Amino acids', 'amino acids'] @entity10175 :: ('3667', 'Gene') :: ['insulin receptor substrate 1', 'IRS-1'] @entity4357 :: ('MESH:D010716', 'Chemical') :: ['phosphatidylinositol'] @entity535 :: ('CHEBI:33704', 'Chemical') :: ['amino acid'] @entity3446 :: ('MESH:D020123', 'Chemical') :: ['rapamycin'] @entity3470 :: ('21977(Tax:10090)', 'Gene') :: ['mTOR'] @entity563 :: ('CHEBI:17822', 'Chemical') :: ['serine'] @entity1889 :: ('CHEBI:26986', 'Chemical') :: ['threonine'] @entity413 :: ('MESH:D005947', 'Chemical') :: ['glucose']
@entity535 :: (CHEBI:33704,Chemical) :: ['Amino acid']
