IndraLab
Statements
sparser
"Prompted by the results from intravenous amino acid infusion studies in people that demonstrated that amino acids blunt insulin-mediated glucose disposal ( xref , xref ) and studies conducted in cultured myotubes and isolated rat skeletal muscles that demonstrated that leucine can impair insulin-mediated glucose uptake ( xref , xref ), presumably mediated by mTOR-p70S6K phosphorylation and subsequent serine phosphorylation of insulin receptor substrate-1 ( xref ), we tested the hypothesis that protein ingestion impairs insulin-mediated glucose disposal by leucine-mediated muscle mTOR signaling in people."
sparser
"Amino acid-induced mammalian target of rapamycin complex-1 (mTORC1) activation causes phosphorylation of insulin receptor substrate-1 (IRS-1), leading to the occurrence of insulin resistance; (4) glucocorticoids promote gluconeogenesis in liver and cause hyperglycemia; and (5) non-specific binding of glucocorticoids to its receptor in the kidneys causes an increase in sodium retention, potassium excretion, water retention, and plasma volume concomitantly with elevation of blood pressure [ xref , xref , xref ]."
rlimsp
"The activation of mTOR phosphorylates its downstream protein ribosomal S6 protein kinase (S6K), participating in several processes including protein synthesis and proliferation [12], [13]. It became apparent that serine phosphorylation of IRS1 reduces the ability of IRS1 to activate PI3K [10]–[12]."
reach
"Notably, hyperactive S6K1 and mTOR negatively regulate Akt by inducing IRS-1 serine phosphorylation (S302 (human 307) [XREF_BIBR], S636/639 [XREF_BIBR], S1101 [XREF_BIBR], S307 (human 312) [XREF_BIBR, XREF_BIBR]), which disrupts its interaction with the insulin receptor, and results in degradation."
reach
"Reduced mTOR and S6K1 signaling during chronic increases in physical activity may play an important regulatory role in the serine phosphorylation of IRS-1, which should be examined as a potential mechanism for attenuation of insulin resistance associated with increased IRS-1 serine phosphorylation."
"These results indicate that activation of protein kinase c stimulates a kinase which can phosphorylate insulin receptor substrate-1 at serine 612, resulting in an inhibition of insulin signaling in the cell these data suggest that: 1) activation of pkctheta contributes to ikk and jnk activation by ffas;2) ikk and jnk mediate pkctheta signals for irs-1 serine phosphorylation and degradation; ser-302 phosphorylation is dependent on pi 3-kinase/mtor, whereas ser-307 depends on c-jun nh2-terminal kinase to inhibit irs1 tyrosine phosphorylation. Ser-636 is located around the pi 3-kinase binding site and, therefore, thought to inhibit pi 3-kinase signaling."
reach
"These include mammalian target of rapamycin (mTOR)-mediated phosphorylation of IRS1 serine 636 (Ser636) and serine 639 (Ser639), ribosomal S6 kinase 1 (S6K1)-mediated phosphorylation of IRS1 serine 307 [Ser307 (mouse serine 302) (Ser302)] and serine 1101, IkappaB kinase beta (IKKbeta) - and c-Jun N-terminal kinase (JNK)-mediated phosphorylation of IRS1 serine 312 [Ser312 (mouse Ser307)], and protein kinase zeta mediated phosphorylation of IRS1 serine 323 (mouse serine 318)."
reach
"The latter mechanism is responsible for the described feedback loop inhibition of Akt phosphorylation mediated by mTOR dependent phosphorylation of IRS-1 at Ser312, the immediate downstream effector protein of the insulin like growth factor-1 receptor (IGF-1R) [XREF_BIBR, XREF_BIBR]."
"Here, we demonstrate that nutrients suppress phosphatidylinositol 3 (PI3)-kinase/Akt signaling via Raptor-dependent mTOR (mammalian target of rapamycin)-mediated phosphorylation of insulin receptor substrate 1 (IRS-1). Raptor directly binds to and serves as a scaffold for mTOR-mediated phosphorylation of IRS-1 on Ser636/639"
reach
"However, Pim1 overexpression did not significantly change the phosphorylation level of ribosomal protein S6 (S240/244), a substrate of activated p70S6K, or phosphorylation of GSK3beta (S9) protein, an AKT substrate, suggesting that the AKT and mTOR signaling pathway did not mediate the phosphorylation of IRS1 on S1101."
reach
"Overfeeding and metabolic stresses, including high levels of free fatty acids or inflammatory cytokines, enable activation of a number of endogenous protein kinases, such as mTOR, JNK, and IKKbeta, which can phosphorylate IRS1 and IRS2 at serine and threonine residues and which mediate IRS protein ubiquitination and degradation, resulting in insulin resistance [XREF_BIBR]."