"Other feedback or alternative signaling loops that mediate resistance involve an mTOR dependent serine phosphorylation of insulin receptor substrate-1 (IRS-1) that enhances insulin like growth factor-1 (IGF-1) signaling leading to downstream activation of PI3K and AKT."
"The activation of mTOR phosphorylates its downstream protein ribosomal S6 protein kinase (S6K), participating in several processes including protein synthesis and proliferation , . It became apparent that serine phosphorylation of IRS1 reduces the ability of IRS1 to activate PI3K –."
"mTOR induced the serine phosphorylation of IRS-1 (Ser 636/639), and such phosphorylation was inhibited by rapamycin."
"TNF-alpha produced by obesity induced inflammation stimulates IKK XREF_BIBR, JNK XREF_BIBR, and mTOR and S6K XREF_BIBR XREF_BIBR, which enhance serine phosphorylation of insulin receptor substrate-1 (IRS-1)."
"Recent studies demonstrate that the mTOR downstream target S6K1 directly phosphorylates IRS1 serine residues, including Ser 302/307, Ser 307/312, Ser 632/636, and Ser 1097/1101."
"In a similar fashion, it was shown that rapamycin induced mTOR inhibition decreased the serine phosphorylation of IRS-1, which was associated with a compensatory IGF-I downstream signaling via the PI3K and AKT pathway [XREF_BIBR]."
"Studies conducted in rodent models and cultured rat myocytes found that increased exposure of skeletal muscle cells to BCAA impairs insulin action in concert with activation of the mammalian target of rapamycin (mTOR), which causes serine phosphorylation of insulin receptor substrate-1 and disrupts insulin signaling."
"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]."
"The mammalian target of rapamycin (mTOR) is downstream of Akt and can phosphorylate IRS1 on serine residues, targeting it for degradation."
"mTOR induced the serine phosphorylation of IRS-1 (Ser-636/639), and such phosphorylation was inhibited by rapamycin."