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FOXO1 — INS

Pathways - manually collected, often from reviews:

• WikiPathways White fat cell differentiation: INS → FOXO1 (unknown)

Text-mined interactions from Literome

Nakae et al., J Biol Chem 1999 : Insulin stimulates phosphorylation of the forkhead transcription factor FKHR on serine 253 through a Wortmannin-sensitive pathway ... Because Akt is phosphorylated in response to insulin and has been implicated in a variety of insulin effects, we investigated whether insulin affects phosphorylation of FKHR ... Insulin stimulated phosphorylation of endogenous FKHR and of a recombinant c-Myc/FKHR fusion protein transiently expressed in murine SV40 transformed hepatocytes ... Mutation of serine 253, located in a consensus Akt phosphorylation site at the carboxyl-terminal end of the forkhead domain, abolished the effect of insulin on FKHR phosphorylation
Guo et al., J Biol Chem 1999 : To our knowledge, these results provide the first report that FKHR stimulates promoter activity through an IRS and that phosphorylation of FKHR by PKB mediates effects of insulin on gene expression
Tomizawa et al., J Biol Chem 2000 : Insulin inhibited FKHR fragment stimulated promoter activity by approximately 70 %
Patel et al., Biochem J 2001 : However insulin induced phosphorylation of PKB or FKHR is not affected by the presence of phorbol esters
Nakae et al., J Clin Invest 2001 : These findings are consistent with the possibility that Foxo1 is involved in insulin regulation of glucose production by mediating the ability of insulin to decrease the glucocorticoid/cAMP response of G6p
Scheimann et al., Horm Metab Res 2001 : Thus, in hepatocytes as in other cell lines, all three FKHR PKB sites participate in insulin mediated inhibition of FKHR action and in insulin mediated accumulation of FKHR in cytoplasm
Patel et al., Biochem J 2002 : However, insulin induced phosphorylation and regulation of protein kinase B, glycogen synthase kinase-3 and FKHR ( forkhead in rhabdomyosarcoma ) are not affected by H ( 2 ) O ( 2 ) in the same cells
Barthel et al., Exp Clin Endocrinol Diabetes 2002 : Construction and characterization of a conditionally active construct of the insulin regulated forkhead transcription factor FKHR
Nakae et al., Dev Cell 2003 (Diabetes Mellitus...) : The forkhead transcription factor Foxo1 is regulated by insulin via Akt dependent phosphorylation and nuclear exclusion
Perrot et al., J Biol Chem 2003 : Insulin inhibition of Foxo1- ( 208-652 ) -stimulated transactivation is mediated by PI 3-kinase but in contrast to full-length Foxo1, does not require either of the two PKB/Akt phosphorylation sites ( Ser253 and Ser316 ) present in the protein fragment ... We conclude that the transcriptional activity of Foxo1 is regulated at different levels by insulin : transactivation, as well as DNA binding and nuclear exclusion
Matsuzaki et al., Proc Natl Acad Sci U S A 2003 : Insulin induced phosphorylation of FKHR ( Foxo1 ) targets to proteasomal degradation ... FKHR is ubiquitinated in vivo and in vitro, and insulin enhances the ubiquitination in the cells ... These results demonstrate that the insulin induced phosphorylation of FKHR leads to the multistep negative regulation, not only by the nuclear exclusion but also the ubiquitination mediated degradation
Tsai et al., Endocrinology 2003 (Carcinoma, Hepatocellular...) : The activity of FOXO proteins is principally regulated by activation of protein kinase B (PKB)/Akt by insulin and other cytokines
Rena et al., EMBO Rep 2004 : Our results indicate that these residues are targeted by CK1 in vivo and that the CK1 mediated phosphorylation of the MPD is required for accelerated nuclear exclusion of FOXO1a in response to IGF-1 and insulin
D'Alessandris et al., FASEB J 2004 : BADGP reversed the glucosamine induced reduction in insulin stimulated phosphorylation of IR, IRS-1, IRS-2, Akt, GSK-3, and FOXO1a
Xu et al., J Biol Chem 2004 : In these protein kinase B/Akt 1 RNA interference cells, the signal molecules upstream of protein kinase B/Akt 1, such as IGF-1 receptor and insulin receptor substrate-1, were normally activated by insulin stimulation, whereas insulin stimulated phosphorylation of forkhead transcription factor (FKHR) , which is a downstream molecule of PKB/Akt 1, was blocked
Altomonte et al., J Clin Invest 2004 (Hypertriglyceridemia) : Moreover, we show that hepatic Foxo1 expression becomes deregulated as a result of insulin deficiency or insulin resistance, culminating in significantly elevated Foxo1 production, along with its skewed nuclear distribution, in livers of diabetic NOD or db/db mice
Kino et al., Diabetes 2005 (Acquired Immunodeficiency Syndrome...) : This HIV-1 protein also interfered with insulin induced coprecipitation of 14-3-3 and Foxo3a in vivo and antagonized the negative effect of insulin on Foxo3a induced transactivation of a FOXO-responsive promoter
Schattenberg et al., J Biol Chem 2005 (Fatty Liver...) : In parallel, the effects of insulin on Akt activation, glycogen synthase kinase 3, and FoxO1a phosphorylation, and glucose secretion were all significantly decreased in CYP2E1 overexpressing cells
van der Heide et al., Trends Biochem Sci 2005 : Forkhead box, class O ( FoxO ) transcription factors are inhibited by insulin induced FoxO phosphorylation
Perrot et al., Mol Endocrinol 2005 : In contrast to its importance in regulating the transcriptional activity of Foxo1 in the absence of insulin, acetylation plays only a minor role compared with phosphorylation in insulin inhibition of Foxo1 transcriptional activity
Mounier et al., Endocrinology 2006 : In these same cells, inhibition of the insulin effect by rapamycin occurred in the presence of insulin induced Foxo1/Foxo3 phosphorylation ... In contrast, 1 nm insulin inhibited the IGFBP-1 mRNA level by 40 % and correspondingly activated Akt and Foxo1/Foxo3 phosphorylation to a level comparable to that observed with 100 nM insulin
Puig et al., Cell cycle (Georgetown, Tex.) 2006 : Nutrient availability and growth : regulation of insulin signaling by dFOXO/FOXO1
Buteau et al., Diabetes 2006 : In contrast, LY294002 but not AG1478 suppressed insulin induced FoxO1 phosphorylation
Cho et al., Cell Metab 2006 (Diabetes Mellitus, Type 2...) : Through the concomitant application of genome-scale functional screening and quantitative image analysis, we have identified PTP-MEG2 as a modulator of insulin dependent FOXO1 subcellular localization
Yamada et al., Biochem Biophys Res Commun 2006 : Adenoviral mediated overexpression of forkhead transcription factor Foxo1 increased angptl4 mRNA expression, and insulin significantly suppressed its effect
Li et al., J Biol Chem 2006 : Insulin regulation of cholesterol 7alpha-hydroxylase expression in human hepatocytes : roles of forkhead box O1 and sterol regulatory element binding protein 1c ... Chromatin immunoprecipitation assay shows that insulin reduced FoxO1 and peroxisome proliferators activated receptor gamma-coactivator-1alpha but increased SREBP-1c recruitment to CYP7A1 chromatin
Guo et al., Mol Endocrinol 2006 : By contrast, insulin stimulation of Irs1 ( -/- ) MEFs caused FoxO degradation, not only because Irs2 expression increased but also because Irs2 efficiently activated p110alpha -- > Akt cascade ... Importantly, prolonged insulin stimulation restored FoxO1 expression in wild-type or Irs1 ( -/- ) MEFs because Irs2 was degraded and Irs1 alone failed to activate sufficient p110alpha to promote the Akt -- > FoxO cascade
Liu et al., J Endocrinol 2007 : FOXO1 is a member of the forkhead transcriptional factor family, but how insulin and IGF-I receptor signaling regulate FOXO1 in cardiomyocytes is not well understood ... Inhibition of phosphatidylinositol 3-kinase/Akt pathway suppressed the effect of insulin and IGF-I on FOXO1 phosphorylation
Yoshiga et al., Mol Endocrinol 2007 : Insulin induced Akt activation and the phosphorylation of forkhead transcription factor ( FKHR/Foxo1 ), a negative regulator of PPARgamma transcription, were up-regulated by SH2-B overexpression, but reduced in SH2-B-deficient MEFs
Adachi et al., Gastroenterology 2007 (Liver Cirrhosis, Experimental...) : Platelet derived growth factor ( PDGF ) or insulin phosphorylates FoxO1 and induces FoxO1 translocation from the nuclei to the cytosol via the PI3K/AKT pathway in HSCs. Constitutively active FoxO1 inhibits proliferation via cell cycle arrest at the G1 phase, whereas dominant negative FoxO1 enhances proliferation of HSCs even in the presence of the PI3K inhibitor LY294002
Okada et al., Proc Natl Acad Sci U S A 2007 (Hyperplasia...) : Although both groups on the high-fat diet developed insulin resistance, beta IRKO, but not beta IGFRKO, mice exhibited poor islet growth consistent with insulin stimulated phosphorylation, nuclear exclusion of FoxO1 , and reduced expression of Pdx-1
Jing et al., Cell Metab 2007 : This interaction enhances insulin stimulated phosphorylation of FOXO1 , which in turn regulates FOXO1 nuclear and cytosolic localization
Ni et al., Proc Natl Acad Sci U S A 2007 (Insulin Resistance) : Importantly, FoxO mediated increases in Akt activity diminish insulin signaling, as manifested by reduced Akt phosphorylation, reduced membrane translocation of Glut4, and decreased insulin triggered glucose uptake
Vihervaara et al., J Mol Biol 2008 : The transcription factor FOXO1 has a central role in the regulation of glucose levels by insulin : reduced insulin signaling causes FOXO1 activation, which increases hepatic glucose production by activating transcription of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase mRNAs
Tremblay et al., Cell Metab 2008 (Cardiomegaly...) : A new study by Ni et al. ( 2007 ) shows that sustained activation of FoxO1 or FoxO3 in cardiomyocytes selectively enhances the activity of Akt/PKB and reduces insulin signaling through inhibition of calcineurin and PP2A
Hansen et al., PLoS Genet 2008 : Long lived daf-2 insulin/IGF-1 receptor mutants require both autophagy and the transcription factor DAF-16/FOXO for their longevity, but we find that autophagy takes place in the absence of DAF-16
Li et al., J Lipid Res 2008 : Insulin or adenovirus mediated expression of constitutively active AKT1 inhibited FoxO1 and Smad3 synergy ... Chromatin immunoprecipitation assay showed that FoxO1 binding to Cyp7a1 chromatin was increased in diabetic rat livers and insulin reduced FoxO1 binding
Fan et al., J Biol Chem 2009 (Insulin Resistance) : Insulin induces FoxO1 phosphorylation and nuclear exportation, which prevents FoxO1-PPARgamma interactions and rescues transrepression
Ropelle et al., J Physiol 2009 (Obesity) : Results demonstrate that acute exercise improved insulin signalling, increasing insulin stimulated Akt and Foxo1 phosphorylation and decreasing PGC-1alpha expression and PGC-1alpha/Foxo1 interaction in the liver of diet induced obesity rats under fasting conditions
Chakrabarti et al., J Biol Chem 2009 : In 3T3-L1 adipocytes, insulin controls nucleo-cytoplasmic shuttling of FoxO1 and regulates its interaction with endogenous ATGL promotors
Ropelle et al., J Physiol 2009 (Body Weight...) : Here, we identify that a high-fat diet impaired insulin induced hypothalamic Foxo1 phosphorylation and degradation, increasing the nuclear Foxo1 activity and hyperphagic response in rats
Li et al., Biochim Biophys Acta 2009 (Insulin Resistance) : Insulin caused rapid exclusion of FoxO1 from the nucleus and resulted in the induction of CYP7A1 mRNA expression, which was blocked by FoxO1-ADA
Jung et al., Biochem Biophys Res Commun 2009 (Hyperinsulinism) : Forkhead transcription factor FoxO1 inhibits insulin- and transforming growth factor-beta stimulated plasminogen activator inhibitor-1 expression
Su et al., Diabetes 2009 (Diabetes Mellitus, Type 2...) : We studied the mechanism by which FoxO1 mediates insulin dependent regulation of IL-1ß expression in cultured macrophages and correlated FoxO1 activity in peritoneal macrophages with IL-1ß production profiles in mice with low-grade inflammation or insulin resistance
Fiorentino et al., Hepatology 2010 (Fatty Liver...) : TACE overexpression significantly impaired insulin dependent phosphorylation of AKT, GSK3, and FoxO1 in mouse hepatocytes
Cleveland et al., Am J Physiol Regul Integr Comp Physiol 2010 : IGF-I and insulin stimulated phosphorylation of FOXO1 and FOXO4 ( P < 0.05 ), which was inhibited by the phosphatidylinositol 3-kinase ( PI 3-kinase ) inhibitor wortmannin, and decreased the abundance of polyubiquitinated proteins by 10-20 % ( P < 0.05 )
Kimura et al., Journal of clinical biochemistry and nutrition 2010 : Insulin dependent phosphorylation or activation of insulin receptor, insulin receptor substrate-1 and -2, phosphatidylinositol 3-kinase, Akt and forkhead in rhabdomyosarcoma were not affected by PQ pre-treatment
Banerjee et al., J Virol 2010 (Hepatitis C) : In this study, we observed that HCV infection of human hepatocytes impaired insulin induced FoxO1 translocation from the nucleus to the cytoplasm and significantly reduced accumulation of FoxA2 in the nucleus
De Souza et al., J Physiol 2010 (Diabetes Mellitus...) : Acute exercise improved insulin signalling, increasing insulin stimulated Akt and Foxo1 phosphorylation and decreasing HNF-4alpha protein levels in the liver of DIO and ob/ob mice under fasting conditions
Kamagate et al., Endocrinology 2010 : Increased FoxO1 activity augments the expression of insulin receptor (IR) and IR substrate (IRS)2, which in turn inhibits FoxO1 activity in response to reduced insulin action
Haeusler et al., J Biol Chem 2010 (Diabetes Mellitus...) : Transcription factor FoxO1 is regulated dually by insulin and nutrients
Kenyon et al., Ann N Y Acad Sci 2010 : However, the mechanisms by which inhibition of insulin/IGF-1 signaling and germline loss activate DAF-16/FOXO are distinct
Oleksiewicz et al., J Appl Toxicol 2011 : By western blotting with phospho-specific antibodies, insulin induced phosphorylation of IRS-1, Akt, p70S6K, S6 ribosomal protein, 4E-BP1, FoxO3a, FoxO1 , p44/42 MAPK and the EGFR
Oiso et al., Biochem Biophys Res Commun 2011 : In HepG2 cells, insulin stimulated phosphorylation of Akt and forkhead box O 1 (FoxO1) was increased by Ky-2
Edmonds et al., Dev Cell 2010 : Reduction in insulin signaling activates DAF-16/FOXO , which represses the transcription of germline and intestinal genes required to deliver PUFAs to oocytes in lipoprotein complexes
Xu et al., PloS one 2010 : SRA in adipocytes increases both glucose uptake and phosphorylation of Akt and FOXO1 in response to insulin
Löw et al., Gen Comp Endocrinol 2011 (Nerve Degeneration) : Longevity increases when FoxO becomes activated in response to reduced insulin/IGF-1 signalling
Meur et al., J Biol Chem 2011 : Nucleo-cytosolic shuttling of FoxO1 directly regulates mouse Ins2 but not Ins1 gene expression in pancreatic beta cells ( MIN6 ) ... A 915-bp glucose-responsive Ins2 promoter was inhibited by constitutively active FoxO1 , an effect unaltered by simultaneous overexpression of PDX1 ... We conclude that nuclear import of FoxO1 contributes to the suppression of Pdx1 and Ins2 gene expression at low glucose, the latter via a previously unsuspected and direct physical interaction with the Ins2 promoter
Senapedis et al., Mol Biol Cell 2011 : Insulin/Akt activation directs phosphorylation and cytoplasmic sequestration of FOXO away from its target genes and serves as an endpoint of a complex signaling network
Yamamoto et al., Aging Cell 2011 : Although extensively studied in Caenorhabditis elegans, no work has yet demonstrated for Drosophila melanogaster whether reduced insulin/IGF signaling (IIS) requires the FOXO transcription factor ( foxo ) to extend lifespan
Wuescher et al., Am J Physiol Endocrinol Metab 2011 : Insulin regulates menin expression, cytoplasmic localization, and interaction with FOXO1 ... This study provides evidence that menin expression and localization are regulated by insulin signaling and that this regulation triggers an increase in its interaction with FOXO1 via Akt with metabolic consequences
Mansisidor et al., PLoS Genet 2011 : Inhibition of insulin signaling results in the activation of DAF-16/FOXO and SKN-1/Nrf transcription factors and increased animal fitness
Galbo et al., PloS one 2011 (Insulin Resistance) : Furthermore, inhibition of PP2A by specific inhibitors increased insulin stimulated activation of Akt and phosphorylation of FoxO1 and Gsk3a
González-Rodríguez et al., Aging Cell 2012 (Anoxia...) : Conversely, insulin receptor mediated Akt/Foxo1 signaling was attenuated in these aged control mice
Kode et al., J Biol Chem 2012 : The Forkhead transcription factor FoxO1 inhibits through its expression in osteoblasts ß-cell proliferation, insulin secretion, and sensitivity
Bong et al., Meat Sci 2012 : Steers showed higher expression levels of insulin signaling phospho-v-akt murine thymoma viral oncogene homolog 1 than bulls but lower protein levels of nuclear Forkhead box O 1 (FoxO1) than bulls, suggesting that increased insulin signaling following castration decreases nuclear FoxO1 levels, leading to downregulation of ATGL gene expression
Miyazaki et al., Genes Cells 2012 : Using these knockout and floxed cell lines, we found that Foxo1 ablation enhanced the glucose stimulated insulin secretion ( GSIS ) at high glucose concentrations and enhanced ß-cell proliferation
Arriola et al., J Biol Chem 2012 : We demonstrated that FOXO1 is expressed in murine gonadotrope cells and that insulin signaling increased FOXO1 phosphorylation and cytoplasmic localization in a PI3K dependent manner ... In summary, we demonstrate that FOXO1 phosphorylation and cellular localization is regulated by insulin signaling in gonadotropes and that FOXO1 inhibits Lhb transcription
Thorn et al., Diabetes 2013 (Fetal Growth Retardation) : Insulin robustly activated AKT, GSK3ß, and forkhead box class O (FOXO)1 in CON and IUGR fetal livers
Lu et al., J Biol Chem 2013 (Insulin Resistance) : In line with the in vivo results, insulin induced AKT and FoxO1 phosphorylation were potentiated by inhibition of Sirt1 in a cultured hypothalamic cell line
Kitamura et al., Nihon rinsho. Japanese journal of clinical medicine 2013 (Obesity) : FoxO1 is a downstream effector of insulin signaling and Sirt1 is an NAD ( + ) -dependent deacetylase, both of which work as energy sensors at the cellular level