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INS — MTOR

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Patel et al., J Biol Chem 2002 : Insulin regulation of insulin-like growth factor binding protein-1 gene expression is dependent on the mammalian target of rapamycin , but independent of ribosomal S6 kinase activity ... Rapamycin inhibited the mammalian target of rapamycin (mTOR) and the subsequent activation of p70/p85 S6 protein kinase-1 (S6K1) by insulin , whereas amino acid depletion prevented insulin induction of these signaling molecules
Patel et al., Biochem J 2002 : Insulin regulation of hepatic insulin-like growth factor binding protein-1 ( IGFBP-1 ) gene expression and mammalian target of rapamycin (mTOR) signalling is impaired by the presence of hydrogen peroxide
Culbert et al., Biochim Biophys Acta 2002 : However, the induction of Fra-1 gene expression by insulin requires both the FRAP/mTOR and MAP kinase pathways
Lawrence et al., Curr Top Microbiol Immunol 2004 : The phosphorylation of mTOR , itself, is stimulated by insulin in Ser2448, a site that is also phosphorylated by protein kinase B (PKB) in vitro and in response to activation of PKB activity in vivo
Gual et al., Diabetologia 2003 : Moreover, inhibition of mTOR led to a persistent PI 3-kinase activation by insulin
Wu et al., J Biol Chem 2004 : Insulin treatment induced p70S6K, mTOR , and Akt phosphorylation, effects that were completely prevented by the PI3K inhibitor, LY294002 ... Insulin induced phosphorylation of p70S6K and mTOR was prevented by the mTOR inhibitor, rapamycin
Proud et al., Biochem Biophys Res Commun 2004 : Insulin decreases the ability of eEF2 kinase to bind calmodulin, its essential activator, and this effect requires mTOR signalling and a novel phosphorylation site in eEF2 kinase, Ser78
Tillmar et al., Mol Cell Biochem 2004 : Thus, our results suggest an involvement of mTOR in glucose induced PTB/ins-PRS binding and insulin mRNA stability
Guillet et al., FASEB J 2004 : Phosphorylation of PKB, mTOR , and 4E-BP1 were similarly increased by insulin and amino acid in both groups, except for S6K1 phosphorylation, which was not stimulated in elderly subjects
Hinault et al., FASEB J 2004 : In addition to amino acids, mTOR is regulated by insulin via a phosphatidylinositol 3-kinase ( PI 3-kinase ) -dependent pathway
Tremblay et al., Endocrinology 2005 : Activation of mTOR/S6K1 by insulin was associated with a rapamycin-sensitive increase in Ser636/639 phosphorylation of insulin receptor substrate (IRS)-1 but, surprisingly, did not result in impaired IRS-1 associated phosphatidylinositol (PI) 3-kinase activity
Khamzina et al., Endocrinology 2005 (Disease Models, Animal...) : Time-course studies also revealed that mTOR and S6K1 activation by insulin was accelerated in tissues of obese rats, in association with increased inhibitory phosphorylation of insulin receptor substrate-1 (IRS-1) on Ser636/Ser639 and impaired Akt activation ... Insulin caused a time dependent activation of mTOR and S6K1 in HepG2 cells
Lee et al., J Biol Chem 2005 : In agreement, insulin rapidly induced the phosphorylation of 3-phosphoinositide dependent protein kinase-1 ( PDK1 ), protein kinase B ( Akt ), and mTOR , effects that were prevented by the AG1024 and LY294002
Smith et al., J Biol Chem 2005 : Recent work demonstrated the importance of the tuberous sclerosis protein TSC2 for regulation of mTOR by insulin
Canettieri et al., Cell Metab 2005 : Dual role of the coactivator TORC2 in modulating hepatic glucose output and insulin signaling ... Here, we show that, in parallel with their effects on glucose output, CREB and TORC2 also enhance insulin signaling in liver by stimulating expression of the insulin receptor substrate 2 (IRS2) gene
Guillen et al., Endocrinology 2006 : In beta-IRLoxP beta-cells, p44/p42 MAPK and phosphatidylinositol 3 kinase pathways, mammalian target of rapamycin (mTOR), and p70S ( 6 ) K phosphorylation and beta-cell proliferation were stimulated in response to insulin
Hinault et al., J Nutr Biochem 2006 (Insulin Resistance) : The aim of this review is to summarize novel findings on the role of mTOR and amino acids in insulin signaling in adipocytes
Wang et al., J Biol Chem 2006 : Activation of mammalian target of rapamycin (mTOR) by insulin is associated with stimulation of 4EBP1 binding to dimeric mTOR complex 1 ... Here we demonstrate that insulin produces a stable increase in the kinase activity of mTORC1 in 3T3-L1 adipocytes ... The stimulatory effects of insulin on both 4EBP1 kinase activity and binding occurred rapidly and at physiological concentrations of insulin, and both effects required an intact mTORC1
Matsushima et al., J Biol Chem 2006 : In cultured cells, overexpression of TRB3 completely inhibited insulin stimulated S6K1 activation by mammalian target of rapamycin , whereas knockdown of endogenous TRB3 increased both basal and insulin stimulated activity ... Both insulin and feeding activated mammalian target of rapamycin similarly in these mice ; however, feeding was unable to activate the downstream target S6K1 in C57BL/6 mice
Varma et al., Biochim Biophys Acta 2007 : Therefore, the effects of insulin and rapamycin ( an inhibitor of mTOR ) on the phosphorylation of mTOR ( Ser 2448 ) and p70 ( S6K ) ( Thr 389 ) as well as on cell proliferation in parental HepG2 cells and HepG2 cells overexpressing constitutively active Akt/PKB ( HepG2-CA-Akt/PKB ) were studied ... Insulin increased the levels of phosphorylated mTOR and p70 ( S6K ) in both the cell lines ... Long term effects of rapamcyin significantly decreased the levels of p-mTOR ( Ser 2448 ) both in the presence and absence of insulin in these cells
Fujita et al., Diabetes 2007 (Insulin Resistance) : Insulin improved Akt phosphorylation in the EX group and increased mTOR/S6 kinase 1 phosphorylation and muscle protein synthesis ( EX group : 49 +/- 11 to 89 +/- 23 ; CTRL group : 58 +/- 8 to 57 +/- 12 nmol x min ( -1 ) x 100 ml leg ( -1 ) ) in the EX group only ( P < 0.05 )
Sancak et al., Mol Cell 2007 : Insulin stimulates Akt/PKB mediated phosphorylation of PRAS40, which prevents its inhibition of mTORC1 in cells and in vitro
Adams et al., J Biol Chem 2007 : Insulin mediated induction of ATF4 required the mammalian target of rapamycin complex 1, was required for the activation of a genetic program for the cellular uptake of essential amino acids and the synthesis of nonessential amino acids and aminoacyl-tRNAs, and was coupled to the repression of Foxo dependent genes needed for protein and lipid catabolism
Fujita et al., J Physiol 2007 : On the other hand, essential amino acids ( leucine in particular ) and insulin stimulate mTOR signalling and protein synthesis
Wang et al., J Biol Chem 2007 : In response to insulin and nutrients, mTORC1 , consisting of mTOR, raptor ( regulatory associated protein of mTOR ), and mLST8, is activated and phosphorylates eukaryotic initiation factor 4E-binding protein ( 4EBP ) and p70 S6 kinase to promote protein synthesis and cell size
Sharma et al., Cardiovasc Res 2007 : Glucose phosphorylation is required for insulin dependent mTOR signalling in the heart ... The anabolic effects of insulin are mediated by the mammalian target of rapamycin (mTOR) , an evolutionarily conserved kinase which is also a convergence point between nutrient sensing and cell growth ... Phosphorylation of glucose is necessary for insulin dependent mTOR activity in the heart, suggesting a link between intermediary metabolism and cardiac growth
Endo et al., Cancer Res 2007 : IGFs and insulin enhanced the endoplasmic reticulum ( ER ) stress response as monitored by induction of the CCAAT/enhancer binding protein homologous protein ( CHOP ) proteins and the X box protein-1 splicing under hypoxic conditions, and this response was suppressed by inhibiting PI3K and mTOR activity
Dentin et al., Nature 2007 (Diabetes Mellitus) : Insulin disrupts TORC2 activity by induction of the Ser/Thr kinase SIK2, which we show here undergoes AKT2 mediated phosphorylation at Ser 358
Suryawan et al., Am J Physiol Endocrinol Metab 2007 : Both INS and AA increased protein synthesis and the phosphorylation of mammalian target of rapamycin (mTOR) , ribosomal protein S6 kinase-1, and eukaryotic initiation factor (eIF)4E binding protein 1 ( 4E-BP1 ), and these responses were higher in 6-day-old compared with 26-day-old pigs
Kim et al., J Biol Chem 2008 (Carcinoma, Hepatocellular...) : Interestingly, we find that the phosphorylation of STAT3 on Ser ( 727 ) and STAT3 transcriptional activity are regulated by mTOR upon IL-6 stimulation and that STAT3 is required for IL-6 inhibition of insulin signaling
Chenal et al., Eur J Neurosci 2008 : Investigation of the putative signalling pathways leading to translation activation revealed that insulin and IGF-1 induced p44- and p42 MAPK, Akt and mTOR phosphorylation
Koketsu et al., Am J Physiol Endocrinol Metab 2008 (Glucose Intolerance...) : In this study, to investigate the effect of mTOR/raptor on insulin signaling and metabolism in K/KAy mice with genetic obesity associated insulin resistance, a dominant negative raptor, COOH-terminally deleted raptor ( raptor-DeltaC ( T ) ), was overexpressed in the liver via injection of its adenovirus into the circulation
Dan et al., J Immunol 2008 : Differential involvement of IkappaB kinases alpha and beta in cytokine- and insulin induced mammalian target of rapamycin activation determined by Akt ... Insulin activation of mTOR requires Akt in a manner that involves IKKalpha, preferentially to IKKbeta, and TSC2 phosphorylation
Avruch et al., Am J Physiol Endocrinol Metab 2009 : Insulin , growth factors, and a variety of cellular stressors regulate mTORC1 by controlling Rheb GTP charging through modulating the activity of the tuberous sclerosis complex, the Rheb GTPase activating protein
Maeurer et al., Cell Signal 2009 : Increased intracellular PAM concentrations facilitated S1P- and insulin induced mTOR activation as well as p70S6K and 4EBP1 phosphorylation while genetic deletion of PAM decreased S1P- and insulin induced mTOR activation
Allemand et al., PloS one 2009 (Insulin Resistance...) : Cells pre exposed to low-dose testosterone had significantly increased insulin induced mTOR-Ser ( 2448 ) and S6K-Thr ( 389 ) phosphorylation ( p < 0.05 ), and further increased insulin induced IRS-1 Ser ( 636/639 ) phosphorylation ( p = 0.042 ) compared to control cells ... High-dose testosterone pre-exposure attenuated the insulin induced mTOR-Ser ( 2448 ) and S6K-Thr ( 389 ) phosphorylation
Ryu et al., Cell Metab 2009 (Glucose Intolerance...) : TORC2 regulates hepatic insulin signaling via a mammalian phosphatidic acid phosphatase, LIPIN1
Zhang et al., Free Radic Biol Med 2009 : In this study we report the effect of H ( 2 ) O ( 2 ) on insulin stimulated mTORC1 activity and assembly using A549 and bovine aortic smooth muscle cells ... These findings are consistent with PRAS40 functioning as a negative regulator of insulin stimulated mTORC1 activity during oxidant stress
Wang et al., J Biol Chem 2009 : Raptor ( regulatory associated protein of mammalian target of rapamycin (mTOR) ), a constitutively binding protein of mTORC1, is essential for mTORC1 activity and critical for the regulation of mTORC1 activity in response to insulin signaling and nutrient and energy sufficiency
Young et al., Autophagy 2009 : We recently reported that the absence of insulin from the culture medium induces autophagy in this primary neuron system, and that the neuronal autophagy activation is mTOR dependent
Acosta-Jaquez et al., Mol Cell Biol 2009 : Here we identify a new site of mTOR phosphorylation ( S1261 ) by tandem mass spectrometry and demonstrate that insulin-phosphatidylinositol 3-kinase signaling promotes mTOR S1261 phosphorylation in both mTORC1 and mTORC2 ... These data provide the first evidence that site-specific mTOR phosphorylation regulates mTORC1 function and suggest a model whereby insulin stimulated mTOR S1261 phosphorylation promotes mTORC1 autokinase activity, substrate phosphorylation, and cell growth
Cybulski et al., Proc Natl Acad Sci U S A 2009 (Fatty Liver) : mTORC2 , which consists of rictor, mSIN1, mLST8, and mTOR, is activated by insulin/IGF1 and phosphorylates Ser-473 in the hydrophobic motif of Akt/PKB
Baum et al., Am J Physiol Endocrinol Metab 2009 : Glucagon acts in a dominant manner to repress insulin induced mammalian target of rapamycin complex 1 signaling in perfused rat liver ... Compared with control livers, insulin stimulated Akt phosphorylation and mTORC1 signaling, as assessed by increased phosphorylation of the mTORC1 targets eIF4E binding protein ( 4E-BP ) 1 and ribosomal protein S6 kinase (S6K)1, and promoted assembly of the eIF4G x eIF4E complex ... Overall, the results suggest that glucagon acts in a dominant manner to repress insulin induced mTORC1 signaling, which is in contrast to previous studies showing a dominant action of insulin in the control of hepatic gluconeogenesis
Zhang et al., PloS one 2009 : In examining the requirements for different Akt mediated phosphorylation sites on TSC2, we find that only TSC2 mutants lacking all five previously identified Akt sites fully block insulin stimulated mTORC1 signaling in reconstituted Tsc2 null cells, and this mutant also inhibits adipogenesis
Stadlbauer et al., Am J Physiol Endocrinol Metab 2009 : We conclude that amino acids can directly affect muscle glucose metabolism via two mechanisms, mTOR/S6K mediated insulin desensitization and mitochondrial substrate competition, with the latter predominating in isolated rat muscle
Mori et al., Am J Physiol Endocrinol Metab 2009 (Insulin Resistance...) : The young Rip-Tsc1cKO animals displayed improved glycemic control due to mTOR mediated enhancement of ß-cell size, mass, and insulin production but not determinants of ß-cell number ( proliferation and apoptosis ), consistent with an important anabolic role for mTOR in ß-cell function
Chotechuang et al., Am J Physiol Endocrinol Metab 2009 : Either AAs or insulin can stimulate p-mTOR , but this is not sufficient for 4E-BP1 phosphorylation that requires both ( P < 0.01 ) ... As expected, branched-chain AAs ( BCAA ) or leucine stimulated the phosphorylation of mTOR , but both insulin and BCAA or leucine are required for 4E-BP1 phosphorylation ... The present findings demonstrate that AAs and insulin exert a coordinated action on translation and involved mTOR , AMPK, and GCN2 transduction pathways
Sanchez Canedo et al., Am J Physiol Endocrinol Metab 2010 : Moreover, the introduction in PDK1 of the L155E mutation, which is known to preserve the insulin induced and PKB/Akt dependent phosphorylation of mTOR/p70 ( S6K ), suppressed all leucine effects, including phosphorylation of mTOR, PRAS40, and p70 ( S6K )
Flinn et al., Mol Biol Cell 2010 : These data suggest that integrity of late endosomes is essential for amino acid- and insulin stimulated mTORC1 signaling and that blocking the early/late endosomal conversion prevents mTOR from interacting with Rheb in the late endosomal compartment
Tao et al., Journal of molecular signaling 2010 : AMPK activation improves insulin sensitivity via multiple mechanisms, among which AMPK suppresses mTOR/S6K mediated negative feedback regulation of insulin signaling ... Our results showed that 5-aminoimidazole-4-carboxamide-1 ribonucleoside ( AICAR ) greatly enhanced the ability of insulin to stimulate the insulin receptor substrate-1 (IRS1) associated PI3K activity in differentiated 3T3-F442a adipocytes, leading to increased Akt phosphorylation at S473, whereas insulin stimulated activation of mTOR was diminished
Kimura et al., Journal of clinical biochemistry and nutrition 2010 : In contrast, PQ treatment impaired insulin dependent phosphorylation of mammalian target of rapamycin (mTOR) ... These results indicate that PQ-induced oxidative stress impairs insulin dependent mTOR activation and that this impairment probably causes inhibition of insulin dependent repression of IGFBP-1 expression
Kumar et al., Diabetes 2010 : To determine the physiological role of rictor/mTORC2 in insulin signaling and action in fat cells, we developed fat cell-specific rictor knockout ( FRic ( -/- ) ) mice
Flati et al., Int J Immunopathol Pharmacol 2010 : Essential amino acids improve insulin activation of AKT/MTOR signaling in soleus muscle of aged rats
Ost et al., Mol Med 2010 (Diabetes Mellitus, Type 2...) : We examined insulin signaling in adipocytes from T2D patients, and contrary to findings in animal studies, we observed attenuation of insulin activation of mammalian target of rapamycin (mTOR) in complex with raptor ( mTORC1 ) ... Conversely, mitochondrial dysfunction attenuated insulin activation of mTORC1 , enhanced autophagy and attenuated feedback to IRS1
Bartolomé et al., Endocrinology 2010 : The use of different beta-cell lines expressing or not the insulin receptor ( IR ( +/+ ) and IR ( -/- ) ) or with a reconstituted expression of IR isoform A or B ( Rec A and Rec B ) revealed that both phosphatidylinositol 3-kinase/Akt/TSC/mTOR complex 1 and MAPK kinase/ERK pathways mediate insulin signaling in IR ( +/+ ) -, IRA-, or IRB expressing cells
Chai et al., Peptides 2010 : Melanocortin-4 receptor activation promotes insulin stimulated mTOR signaling ... The effect of MC4R on insulin stimulated mammalian target of rapamycin (mTOR) , a cellular energy sensor, signaling was investigated ... NDP-MSH dose-dependently enhanced insulin stimulated mTOR phosphorylation ... The protein kinase A - cyclic AMP pathway and the MAP kinase pathway were not involved in NDP-MSH actions on insulin stimulated mTOR phosphorylation ... MC4R activation potentiates insulin stimulated mTOR signaling via the AMPK pathway
Suryawan et al., J Appl Physiol 2010 : The present study aimed to characterize in more detail the effects of the postprandial rise in INS and AA on the activation and abundance of mTORC1 regulators in muscle and how this is modified by development
Timmerman et al., Diabetes 2010 : This defect is associated with impaired insulin induced vasodilation and mTORC1 signaling
An et al., Cell Physiol Biochem 2010 : The mammalian target of rapamycin (mTOR) is activated by insulin
Lightell et al., Endocrinology 2011 : We also examined changes in the response of L2-VSMCs to insulin stimulation and to inhibition of the mammalian target of rapamycin (mTOR) , a kinase critical in VSMC proliferation and migration
Dennis et al., J Biol Chem 2011 : Mechanisms involved in the coordinate regulation of mTORC1 by insulin and amino acids ... In this study, we explored the coordinate regulation of mTORC1 by insulin and amino acids
Ramírez-Rangel et al., Mol Cell Biol 2011 : GRp58/ERp57 knockdown reduces mTORC1 levels and phosphorylation of 4E-BP1 and p70 ( S6K ) in response to insulin
Wu et al., J Biol Chem 2011 : Here we show the activation of p38ß participates in activation of mTOR complex 1 (mTORC1) induced by arsenite but not insulin , nutrients, anisomycin, or H ( 2 ) O ( 2 )
Koyanagi et al., PloS one 2011 : Activation of mTORC1 by TSC2 ablation increases mitochondrial biogenesis and enhances insulin secretion from pancreatic beta cells
Rapley et al., J Biol Chem 2011 : Insulin activation of mTOR complex 1 is accompanied by enhanced binding of substrates ... We examined the mechanism and contribution of this enhancement to insulin activation of mTORC1 signaling in 293E and HeLa cells
LeCapitaine et al., J Infect Dis 2011 (Alcoholism...) : SIV infection induced an inflammatory and pro-oxidative milieu in skeletal muscle, which was associated with decreased insulin stimulated phosphatidylinositol 3-kinase (PI-3k) activity and upregulated gene expression of mTOR and atrogin-1, and protein expression of Ub-proteasome system 19S base
Glidden et al., J Biol Chem 2012 : p300 mediated acetylation of Rictor increases mTORC2 activity toward Akt, whereas site directed mutants within the acetylation region of Rictor exhibit reduced insulin-like growth factor 1 (IGF-1) stimulated mTORC2 kinase activity
He et al., Ann Oncol 2012 (Breast Neoplasms...) : Human epidermal growth factor receptor ( HER2 ), insulin receptor and IGF-I receptor involve the same PI3K/AKT/mTOR signaling , and different antidiabetic pharmacotherapy may differentially affect this pathway, leading to different prognoses of HER2+ breast cancer
Mori et al., Methods Mol Biol 2012 (Disease Models, Animal...) : The young Rip-Tsc1cKO animals displayed improved glycemic control due to mTOR mediated enhancement of ß-cell size and insulin production, but not ß-cell number consistent with an important anabolic role for mTOR in ß-cell function
Zhang et al., Proc Natl Acad Sci U S A 2012 : GPAT1 overexpression impaired insulin stimulated phosphorylation of Akt-S473 and -T308, diminished insulin-suppression of glucose production, significantly inhibited mTOR complex 2 (mTORC2) activity and decreased the association of mTOR and rictor
Pereira et al., Mol Cell Endocrinol 2012 (Insulin Resistance) : mTOR inhibition with rapamycin causes impaired insulin signalling and glucose uptake in human subcutaneous and omental adipocytes
Wu et al., J Biol Chem 2012 : Although expression of the Raptor T908A mutant did not affect the mTORC1 integrity, it markedly impaired the mTORC1 activation by insulin or by overexpression of the small GTP binding protein RheB under nutrient starvation
Melnik et al., World journal of diabetes 2012 : High consumption of leucine-rich proteins explains exaggerated mTORC1 dependent insulin secretion, increased ß-cell growth and ß-cell proliferation promoting an early onset of replicative ß-cell senescence with subsequent ß-cell apoptosis
Watterson et al., Neurosignals 2013 (Anorexia) : Activation of mammalian target of rapamycin 1 (mTORC1) by nutrients, insulin and leptin leads to appetite suppression ( anorexia ) ... Ghrelin mediates an AMPK dependent decrease in mTORC1 activity and increases hypothalamic AgRP mRNA levels, the latter effect being prevented by insulin in an mTORC1 dependent manner
Melnik et al., J Obes 2012 : Leucine thus functions as a maternal-neonatal relay for mTORC1 dependent neonatal ß-cell proliferation and insulin secretion
Chong et al., Cardiovascular diabetology 2012 (Cardiovascular Diseases...) : In the cardiovascular and metabolic systems, mTOR and its multi-protein complexes of TORC1 and TORC2 regulate insulin release and signaling, endothelial cell survival and growth, cardiomyocyte proliferation, resistance to ß-cell injury, and cell longevity
Pan et al., Cell cycle (Georgetown, Tex.) 2012 (Precursor Cell Lymphoblastic Leukemia-Lymphoma) : Human insulin and analogs activated AKT/mTOR signaling and stimulated ALL cell proliferation ( as measured by flow cytometric methods ), but metformin and rosiglitazone blocked AKT/mTOR signaling and inhibited proliferation
Haas et al., Cell Metab 2012 (Diabetes Mellitus, Type 2...) : Liver insulin receptor knockout ( LIRKO ) mice show that in the physiological context of feeding, hepatic insulin signaling is not required for the induction of mTORC1 , an upstream activator of the lipogenic regulator, SREBP-1c
Yuan et al., J Biol Chem 2012 (Insulin Resistance) : Lrictor ( KO ) mice also manifest defects in insulin activated mTORC1 activity, evidenced by decreased S6 kinase and Lipin1 phosphorylation
Lai et al., Biochem J 2012 : In contrast, Akti only modestly inhibited insulin induced PKB and mTOR ( mammalian target of rapamycin ) signalling, with little or no effect on glucose uptake and protein synthesis
Laplante et al., Cell Metab 2012 (Obesity) : DEPTOR activates the proadipogenic Akt/PKB-PPAR-? axis by dampening mTORC1 mediated feedback inhibition of insulin signaling
Fox et al., Invest Ophthalmol Vis Sci 2012 (Diabetes Mellitus, Experimental...) : The biochemical and biophysical mechanisms underlying the actions of PA on insulin activated mTOR/p70 S6Kinase signaling were determined using R28 retinal neuronal cells
Zhang et al., Breast Cancer Res Treat 2012 (Breast Neoplasms) : Subsequent studies revealed that NDGA may also direct target mTORC1 complex because NDGA suppressed amino acids- and insulin stimulated mTORC1 and acted like rapamycin to disrupt mTOR-Raptor interaction
Le Bacquer et al., J Endocrinol 2013 (Hyperglycemia) : mTORC1 and mTORC2 regulate insulin secretion through Akt in INS-1 cells ... mTORC1 and mTORC2 regulate insulin secretion through Akt in INS-1 cells
Kim et al., Mol Cell 2012 : Here, we found that mTORC2 can also regulate insulin signaling at the level of insulin receptor substrate-1 (IRS-1)
Li et al., Mol Nutr Food Res 2013 (Body Weight...) : Chronic leucine supplementation did not enhance insulin receptor substract-1 (IRS-1) phosphorylation on serine 302, but elevated basal IRS-1 phosphorylation on tyrosine 632 and improved insulin stimulated protein kinase B ( Akt ) and mammalian target of rapamycin (mTOR) phosphorylation in liver, skeletal muscle, and adipose tissue of rats on HFD rats, indicating leucine supplementation prevented HFD induced insulin resistance in insulin-target tissues
Demeulder et al., Biochim Biophys Acta 2013 (Myocardial Ischemia) : Ischemia decreased insulin induced mTOR-p70S6K phosphorylation in WT and AMPKa2 KO mice to a similar extent
O' Neill et al., Exp Gerontol 2013 (Alzheimer Disease) : Therapeutic approaches targeted at normalizing signaling through either the neuronal PI3-kinase/Akt/mTOR pathway or its activation by insulin and IGF-1 have been shown to be protective against the development of AD pathology and cognitive decline in animal models of AD and some of these therapies are entering clinical trials in patients with the disease
Melnik et al., Hautarzt 2013 (Acne Vulgaris...) : mTORC1 , the central hub of protein- and lipid biosynthesis, cell growth and proliferation, is activated by insulin , IGF-1 and branched-chain essential amino acids, especially leucine
White et al., Am J Physiol Endocrinol Metab 2013 (Cachexia...) : However, insulin induction of mTOR activity was maintained in IL-6 treated myotubes
Sen et al., Journal of the American Heart Association 2013 : We have previously shown that hexose-6-phosphate levels regulate mammalian target of rapamycin (mTOR) activation in response to insulin
Sekine et al., J Nutr Sci Vitaminol (Tokyo) 2013 : Dietary MCT promotes insulin secretion from the pancreas, and insulin activates mammalian target of rapamycin (mTOR) complex 1 ( mTORC1 ) via the activation of phosphoinositide 3-kinase (PI3K) and its downstream effecter, Akt
Qi et al., Eur J Pharmacol 2013 : Activation of mTOR by insulin or inhibition of endogenous TSC2 levels by siRNA obviously delayed PAB induced senescence
Scott et al., Proc Natl Acad Sci U S A 1998 : Evidence of insulin stimulated phosphorylation and activation of the mammalian target of rapamycin mediated by a protein kinase B signaling pathway ... The effects of insulin on the mammalian target of rapamycin , mTOR, were investigated in 3T3-L1 adipocytes ... The effects of insulin on increasing mTOR protein kinase activity and on decreasing mTAb1 reactivity were abolished by incubating mTOR with protein phosphatase 1
Scott et al., J Biol Chem 1998 : Both forskolin and 8- ( 4-chlorophenylthio ) adenosine 3'-5'-monophosphate ( CPT-cAMP ) prevented the activation of mTOR by insulin in adipocytes, but neither agent affected mTOR activity when added directly to the immunopurified protein ... Forskolin and CPT-cAMP blocked the effect of insulin on increasing mTOR phosphorylation, which was assessed using mTAb1, an antibody whose binding is inhibited by phosphorylation of mTOR