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Gene Information
Gene symbol: FOXO1
Gene name: forkhead box O1
HGNC ID: 3819
Synonyms: FKH1
Related Genes
Related Sentences
| # | PMID | Sentence |
| 1 | 9353126 | The probable human orthologues of DAF-16, FKHR and AFX, may also act downstream of insulin signalling and cooperate with TGF-beta effectors in mediating metabolic regulation. |
| 2 | 10480625 | Conservation of an insulin response unit between mouse and human glucose-6-phosphatase catalytic subunit gene promoters: transcription factor FKHR binds the insulin response sequence. |
| 3 | 10480625 | Because overexpression of the glucose-6-phosphatase catalytic subunit (G-6-Pase) in both type 1 and type 2 diabetes may contribute to the characteristic increased rate of hepatic glucose production, we have investigated whether the insulin response unit (IRU) identified in the mouse G-6-Pase promoter is conserved in the human promoter. |
| 4 | 10480625 | We have previously shown that the accessory factor binding region A is hepatocyte nuclear factor-1, and we show here that the forkhead protein FKHR is a candidate for the insulin-responsive transcription factor binding region B. |
| 5 | 10480625 | Conservation of an insulin response unit between mouse and human glucose-6-phosphatase catalytic subunit gene promoters: transcription factor FKHR binds the insulin response sequence. |
| 6 | 10480625 | Because overexpression of the glucose-6-phosphatase catalytic subunit (G-6-Pase) in both type 1 and type 2 diabetes may contribute to the characteristic increased rate of hepatic glucose production, we have investigated whether the insulin response unit (IRU) identified in the mouse G-6-Pase promoter is conserved in the human promoter. |
| 7 | 10480625 | We have previously shown that the accessory factor binding region A is hepatocyte nuclear factor-1, and we show here that the forkhead protein FKHR is a candidate for the insulin-responsive transcription factor binding region B. |
| 8 | 10689893 | As suggested by the genetic studies in C. elegans, it was recently demonstrated that FKHR, FKHRL1 and AFX, which are mammalian homologues of daf-16 forkhead transcription factor, function downstream of insulin signaling and Akt/PKB under cellular conditions. |
| 9 | 10973497 | DAF-16 recruits the CREB-binding protein coactivator complex to the insulin-like growth factor binding protein 1 promoter in HepG2 cells. |
| 10 | 10973497 | Insulin negatively regulates expression of the insulin-like growth factor binding protein 1 (IGFBP-1) gene by means of an insulin-responsive element (IRE) that also contributes to glucocorticoid stimulation of this gene. |
| 11 | 10973497 | We find that the Caenorhabditis elegans protein DAF-16 binds the IGFBP-1 small middle dotIRE with specificity similar to that of the forkhead (FKH) factor(s) that act both to enhance glucocorticoid responsiveness and to mediate the negative effect of insulin at this site. |
| 12 | 10973497 | In HepG2 cells, DAF-16 and its mammalian homologs, FKHR, FKHRL1, and AFX, activate transcription through the IGFBP-1.IRE; this effect is inhibited by the viral oncoprotein E1A, but not by mutants of E1A that fail to interact with the coactivator p300/CREB-binding protein (CBP). |
| 13 | 10973497 | We show that DAF-16 and FKHR can interact with both the KIX and E1A/SRC interaction domains of p300/CBP, as well as the steroid receptor coactivator (SRC). |
| 14 | 10973497 | A C-terminal deletion mutant of DAF-16 that is nonfunctional in C. elegans fails to bind the KIX domain of CBP, fails to activate transcription through the IGFBP-1.IRE, and inhibits activation of the IGFBP-1 promoter by glucocorticoids. |
| 15 | 10973497 | Although AFX interacts with the KIX domain of CBP, it does not interact with SRC and does not respond to glucocorticoids or insulin. |
| 16 | 10973497 | Thus, we conclude that DAF-16 and FKHR act as accessory factors to the glucocorticoid response, by recruiting the p300/CBP/SRC coactivator complex to an FKH factor site in the IGFBP-1 promoter, which allows the cell to integrate the effects of glucocorticoids and insulin on genes that carry this site. |
| 17 | 10973497 | DAF-16 recruits the CREB-binding protein coactivator complex to the insulin-like growth factor binding protein 1 promoter in HepG2 cells. |
| 18 | 10973497 | Insulin negatively regulates expression of the insulin-like growth factor binding protein 1 (IGFBP-1) gene by means of an insulin-responsive element (IRE) that also contributes to glucocorticoid stimulation of this gene. |
| 19 | 10973497 | We find that the Caenorhabditis elegans protein DAF-16 binds the IGFBP-1 small middle dotIRE with specificity similar to that of the forkhead (FKH) factor(s) that act both to enhance glucocorticoid responsiveness and to mediate the negative effect of insulin at this site. |
| 20 | 10973497 | In HepG2 cells, DAF-16 and its mammalian homologs, FKHR, FKHRL1, and AFX, activate transcription through the IGFBP-1.IRE; this effect is inhibited by the viral oncoprotein E1A, but not by mutants of E1A that fail to interact with the coactivator p300/CREB-binding protein (CBP). |
| 21 | 10973497 | We show that DAF-16 and FKHR can interact with both the KIX and E1A/SRC interaction domains of p300/CBP, as well as the steroid receptor coactivator (SRC). |
| 22 | 10973497 | A C-terminal deletion mutant of DAF-16 that is nonfunctional in C. elegans fails to bind the KIX domain of CBP, fails to activate transcription through the IGFBP-1.IRE, and inhibits activation of the IGFBP-1 promoter by glucocorticoids. |
| 23 | 10973497 | Although AFX interacts with the KIX domain of CBP, it does not interact with SRC and does not respond to glucocorticoids or insulin. |
| 24 | 10973497 | Thus, we conclude that DAF-16 and FKHR act as accessory factors to the glucocorticoid response, by recruiting the p300/CBP/SRC coactivator complex to an FKH factor site in the IGFBP-1 promoter, which allows the cell to integrate the effects of glucocorticoids and insulin on genes that carry this site. |
| 25 | 10973497 | DAF-16 recruits the CREB-binding protein coactivator complex to the insulin-like growth factor binding protein 1 promoter in HepG2 cells. |
| 26 | 10973497 | Insulin negatively regulates expression of the insulin-like growth factor binding protein 1 (IGFBP-1) gene by means of an insulin-responsive element (IRE) that also contributes to glucocorticoid stimulation of this gene. |
| 27 | 10973497 | We find that the Caenorhabditis elegans protein DAF-16 binds the IGFBP-1 small middle dotIRE with specificity similar to that of the forkhead (FKH) factor(s) that act both to enhance glucocorticoid responsiveness and to mediate the negative effect of insulin at this site. |
| 28 | 10973497 | In HepG2 cells, DAF-16 and its mammalian homologs, FKHR, FKHRL1, and AFX, activate transcription through the IGFBP-1.IRE; this effect is inhibited by the viral oncoprotein E1A, but not by mutants of E1A that fail to interact with the coactivator p300/CREB-binding protein (CBP). |
| 29 | 10973497 | We show that DAF-16 and FKHR can interact with both the KIX and E1A/SRC interaction domains of p300/CBP, as well as the steroid receptor coactivator (SRC). |
| 30 | 10973497 | A C-terminal deletion mutant of DAF-16 that is nonfunctional in C. elegans fails to bind the KIX domain of CBP, fails to activate transcription through the IGFBP-1.IRE, and inhibits activation of the IGFBP-1 promoter by glucocorticoids. |
| 31 | 10973497 | Although AFX interacts with the KIX domain of CBP, it does not interact with SRC and does not respond to glucocorticoids or insulin. |
| 32 | 10973497 | Thus, we conclude that DAF-16 and FKHR act as accessory factors to the glucocorticoid response, by recruiting the p300/CBP/SRC coactivator complex to an FKH factor site in the IGFBP-1 promoter, which allows the cell to integrate the effects of glucocorticoids and insulin on genes that carry this site. |
| 33 | 11124266 | In Caenorhabditis elegans, an insulin-like signaling pathway to phosphatidylinositol 3-kinase (PI 3-kinase) and AKT negatively regulates the activity of DAF-16, a Forkhead transcription factor. |
| 34 | 11124266 | We show that in mammalian cells, C. elegans DAF-16 is a direct target of AKT and that AKT phosphorylation generates 14-3-3 binding sites and regulates the nuclear/cytoplasmic distribution of DAF-16 as previously shown for its mammalian homologs FKHR and FKHRL1. |
| 35 | 11124266 | In vitro, interaction of AKT- phosphorylated DAF-16 with 14-3-3 prevents DAF-16 binding to its target site in the insulin-like growth factor binding protein-1 gene, the insulin response element. |
| 36 | 11124266 | In HepG2 cells, insulin signaling to PI 3-kinase/AKT inhibits the ability of a GAL4 DNA binding domain/DAF-16 fusion protein to activate transcription via the insulin-like growth factor binding protein-1-insulin response element, but not the GAL4 DNA binding site, which suggests that insulin inhibits the interaction of DAF-16 with its cognate DNA site. |
| 37 | 11124266 | Elimination of the DAF-16/1433 association by mutation of the AKT/14-3-3 sites in DAF-16, prevents 14-3-3 inhibition of DAF-16 DNA binding and insulin inhibition of DAF-16 function. |
| 38 | 11352721 | It is the first structure of the DNA binding domain from a small subfamily of forkhead transcription factors (i.e., AFX, FKHR, FKHRL1, FKHRL1P1, and FKHRP1). |
| 39 | 11352721 | Despite rather low sequence identity for a protein within the forkhead family, the structure is remarkably similar to those of the DNA binding domains of HNF3-gamma and FREAC-11, and to a lesser extent the DNA binding domain of Genesis which displays a slightly altered orientation of the DNA recognition helix. |
| 40 | 11518806 | Glucose-dependent insulinotropic polypeptide is a growth factor for beta (INS-1) cells by pleiotropic signaling. |
| 41 | 11518806 | Activation of the G-protein-coupled receptor for glucose-dependent insulinotropic polypeptide facilitates insulin-release from pancreatic beta-cells. |
| 42 | 11518806 | In the present study, we examined whether glucose-dependent insulinotropic polypeptide also acts as a growth factor for the beta-cell line INS-1. |
| 43 | 11518806 | Glucose-dependent insulinotropic polypeptide stimulated the signaling modules of PKA/cAMP regulatory element binder, MAPK, and PI3K/protein kinase B in a glucose- and dose-dependent manner. |
| 44 | 11518806 | Janus kinase 2 and signal transducer and activators of transcription 5/6 pathways were not stimulated by glucose-dependent insulinotropic polypeptide. |
| 45 | 11518806 | Activation of PI3K by glucose-dependent insulinotropic polypeptide and glucose was associated with insulin receptor substrate isoforms insulin receptor substrate-2 and growth factor bound-2 associated binder-1 and PI3K isoforms p85alpha, p110alpha, p110beta, and p110gamma. |
| 46 | 11518806 | Downstream of PI3K, glucose-dependent insulinotropic polypeptide-stimulated protein kinase Balpha and protein kinase Bbeta isoforms and phosphorylated glycogen synthase kinase-3, forkhead transcription factor FKHR, and p70S6K. |
| 47 | 11518806 | These data indicate that glucose-dependent insulinotropic polypeptide functions synergistically with glucose as a pleiotropic growth factor for insulin-producing beta-cells, which may play a role for metabolic adaptations of insulin-producing cells during type II diabetes. |
| 48 | 11570877 | Insulin regulation of gene expression through the forkhead transcription factor Foxo1 (Fkhr) requires kinases distinct from Akt. |
| 49 | 11570877 | Insulin inhibits expression of certain liver genes through the phosphoinositol (PI) 3-kinase/Akt pathway. |
| 50 | 11570877 | The forkhead proteins (Foxo1, Foxo3, and Foxo4, previously known as Fkhr or Afx) are transcriptional enhancers, the activity of which is inhibited by insulin through phosphorylation-dependent translocation and nuclear exclusion. |
| 51 | 11570877 | We have also shown that T(24) fails to be phosphorylated in hepatocytes lacking insulin receptors, and we have suggested that this residue is targeted by a kinase distinct from Akt. |
| 52 | 11570877 | In this study, we have further analyzed the ability of Akt to phosphorylate different Foxo1 sites in control and insulin receptor-deficient hepatocytes. |
| 53 | 11570877 | Expression of a dominant negative Akt (Akt-AA) in control hepatocytes led to complete inhibition of endogenous Akt, but failed to inhibit Foxo1 T(24) phosphorylation and, consequently, insulin suppression of IGFBP-1 promoter activity. |
| 54 | 11570877 | Conversely, expression of a constitutively active Akt (Akt-Myr) in insulin receptor-deficient hepatocytes led to an overall increase in the level of Foxo1 phosphorylation, but failed to induce T(24) and S(316) phosphorylation. |
| 55 | 11570877 | These data indicate that the Foxo1 T(24) and S(316) kinases are distinct from Akt, and suggest that the pathways required for insulin regulation of hepatic gene expression diverge downstream of PI 3-kinase. |
| 56 | 11570877 | Insulin regulation of gene expression through the forkhead transcription factor Foxo1 (Fkhr) requires kinases distinct from Akt. |
| 57 | 11570877 | Insulin inhibits expression of certain liver genes through the phosphoinositol (PI) 3-kinase/Akt pathway. |
| 58 | 11570877 | The forkhead proteins (Foxo1, Foxo3, and Foxo4, previously known as Fkhr or Afx) are transcriptional enhancers, the activity of which is inhibited by insulin through phosphorylation-dependent translocation and nuclear exclusion. |
| 59 | 11570877 | We have also shown that T(24) fails to be phosphorylated in hepatocytes lacking insulin receptors, and we have suggested that this residue is targeted by a kinase distinct from Akt. |
| 60 | 11570877 | In this study, we have further analyzed the ability of Akt to phosphorylate different Foxo1 sites in control and insulin receptor-deficient hepatocytes. |
| 61 | 11570877 | Expression of a dominant negative Akt (Akt-AA) in control hepatocytes led to complete inhibition of endogenous Akt, but failed to inhibit Foxo1 T(24) phosphorylation and, consequently, insulin suppression of IGFBP-1 promoter activity. |
| 62 | 11570877 | Conversely, expression of a constitutively active Akt (Akt-Myr) in insulin receptor-deficient hepatocytes led to an overall increase in the level of Foxo1 phosphorylation, but failed to induce T(24) and S(316) phosphorylation. |
| 63 | 11570877 | These data indicate that the Foxo1 T(24) and S(316) kinases are distinct from Akt, and suggest that the pathways required for insulin regulation of hepatic gene expression diverge downstream of PI 3-kinase. |
| 64 | 11570877 | Insulin regulation of gene expression through the forkhead transcription factor Foxo1 (Fkhr) requires kinases distinct from Akt. |
| 65 | 11570877 | Insulin inhibits expression of certain liver genes through the phosphoinositol (PI) 3-kinase/Akt pathway. |
| 66 | 11570877 | The forkhead proteins (Foxo1, Foxo3, and Foxo4, previously known as Fkhr or Afx) are transcriptional enhancers, the activity of which is inhibited by insulin through phosphorylation-dependent translocation and nuclear exclusion. |
| 67 | 11570877 | We have also shown that T(24) fails to be phosphorylated in hepatocytes lacking insulin receptors, and we have suggested that this residue is targeted by a kinase distinct from Akt. |
| 68 | 11570877 | In this study, we have further analyzed the ability of Akt to phosphorylate different Foxo1 sites in control and insulin receptor-deficient hepatocytes. |
| 69 | 11570877 | Expression of a dominant negative Akt (Akt-AA) in control hepatocytes led to complete inhibition of endogenous Akt, but failed to inhibit Foxo1 T(24) phosphorylation and, consequently, insulin suppression of IGFBP-1 promoter activity. |
| 70 | 11570877 | Conversely, expression of a constitutively active Akt (Akt-Myr) in insulin receptor-deficient hepatocytes led to an overall increase in the level of Foxo1 phosphorylation, but failed to induce T(24) and S(316) phosphorylation. |
| 71 | 11570877 | These data indicate that the Foxo1 T(24) and S(316) kinases are distinct from Akt, and suggest that the pathways required for insulin regulation of hepatic gene expression diverge downstream of PI 3-kinase. |
| 72 | 11570877 | Insulin regulation of gene expression through the forkhead transcription factor Foxo1 (Fkhr) requires kinases distinct from Akt. |
| 73 | 11570877 | Insulin inhibits expression of certain liver genes through the phosphoinositol (PI) 3-kinase/Akt pathway. |
| 74 | 11570877 | The forkhead proteins (Foxo1, Foxo3, and Foxo4, previously known as Fkhr or Afx) are transcriptional enhancers, the activity of which is inhibited by insulin through phosphorylation-dependent translocation and nuclear exclusion. |
| 75 | 11570877 | We have also shown that T(24) fails to be phosphorylated in hepatocytes lacking insulin receptors, and we have suggested that this residue is targeted by a kinase distinct from Akt. |
| 76 | 11570877 | In this study, we have further analyzed the ability of Akt to phosphorylate different Foxo1 sites in control and insulin receptor-deficient hepatocytes. |
| 77 | 11570877 | Expression of a dominant negative Akt (Akt-AA) in control hepatocytes led to complete inhibition of endogenous Akt, but failed to inhibit Foxo1 T(24) phosphorylation and, consequently, insulin suppression of IGFBP-1 promoter activity. |
| 78 | 11570877 | Conversely, expression of a constitutively active Akt (Akt-Myr) in insulin receptor-deficient hepatocytes led to an overall increase in the level of Foxo1 phosphorylation, but failed to induce T(24) and S(316) phosphorylation. |
| 79 | 11570877 | These data indicate that the Foxo1 T(24) and S(316) kinases are distinct from Akt, and suggest that the pathways required for insulin regulation of hepatic gene expression diverge downstream of PI 3-kinase. |
| 80 | 11570877 | Insulin regulation of gene expression through the forkhead transcription factor Foxo1 (Fkhr) requires kinases distinct from Akt. |
| 81 | 11570877 | Insulin inhibits expression of certain liver genes through the phosphoinositol (PI) 3-kinase/Akt pathway. |
| 82 | 11570877 | The forkhead proteins (Foxo1, Foxo3, and Foxo4, previously known as Fkhr or Afx) are transcriptional enhancers, the activity of which is inhibited by insulin through phosphorylation-dependent translocation and nuclear exclusion. |
| 83 | 11570877 | We have also shown that T(24) fails to be phosphorylated in hepatocytes lacking insulin receptors, and we have suggested that this residue is targeted by a kinase distinct from Akt. |
| 84 | 11570877 | In this study, we have further analyzed the ability of Akt to phosphorylate different Foxo1 sites in control and insulin receptor-deficient hepatocytes. |
| 85 | 11570877 | Expression of a dominant negative Akt (Akt-AA) in control hepatocytes led to complete inhibition of endogenous Akt, but failed to inhibit Foxo1 T(24) phosphorylation and, consequently, insulin suppression of IGFBP-1 promoter activity. |
| 86 | 11570877 | Conversely, expression of a constitutively active Akt (Akt-Myr) in insulin receptor-deficient hepatocytes led to an overall increase in the level of Foxo1 phosphorylation, but failed to induce T(24) and S(316) phosphorylation. |
| 87 | 11570877 | These data indicate that the Foxo1 T(24) and S(316) kinases are distinct from Akt, and suggest that the pathways required for insulin regulation of hepatic gene expression diverge downstream of PI 3-kinase. |
| 88 | 11570877 | Insulin regulation of gene expression through the forkhead transcription factor Foxo1 (Fkhr) requires kinases distinct from Akt. |
| 89 | 11570877 | Insulin inhibits expression of certain liver genes through the phosphoinositol (PI) 3-kinase/Akt pathway. |
| 90 | 11570877 | The forkhead proteins (Foxo1, Foxo3, and Foxo4, previously known as Fkhr or Afx) are transcriptional enhancers, the activity of which is inhibited by insulin through phosphorylation-dependent translocation and nuclear exclusion. |
| 91 | 11570877 | We have also shown that T(24) fails to be phosphorylated in hepatocytes lacking insulin receptors, and we have suggested that this residue is targeted by a kinase distinct from Akt. |
| 92 | 11570877 | In this study, we have further analyzed the ability of Akt to phosphorylate different Foxo1 sites in control and insulin receptor-deficient hepatocytes. |
| 93 | 11570877 | Expression of a dominant negative Akt (Akt-AA) in control hepatocytes led to complete inhibition of endogenous Akt, but failed to inhibit Foxo1 T(24) phosphorylation and, consequently, insulin suppression of IGFBP-1 promoter activity. |
| 94 | 11570877 | Conversely, expression of a constitutively active Akt (Akt-Myr) in insulin receptor-deficient hepatocytes led to an overall increase in the level of Foxo1 phosphorylation, but failed to induce T(24) and S(316) phosphorylation. |
| 95 | 11570877 | These data indicate that the Foxo1 T(24) and S(316) kinases are distinct from Akt, and suggest that the pathways required for insulin regulation of hepatic gene expression diverge downstream of PI 3-kinase. |
| 96 | 11696581 | The forkhead transcription factor Foxo1 (Fkhr) confers insulin sensitivity onto glucose-6-phosphatase expression. |
| 97 | 11696581 | The latter result in transcriptional suppression of key gluconeogenetic and glycogenolytic enzymes, phosphoenolpyruvate carboxykinase (Pepck) and glucose-6-phosphatase (G6p). |
| 98 | 11696581 | The inability to respond to insulin is associated with reduced expression of the forkhead transcription factor Foxo1, a substrate of the Akt kinase that is inhibited by insulin through phosphorylation. |
| 99 | 11696581 | Transduction of kidney cells with recombinant adenovirus encoding Foxo1 results in insulin inhibition of dex/cAMP-induced G6p expression. |
| 100 | 11696581 | Moreover, expression of dominant negative Foxo1 mutant results in partial inhibition of dex/cAMP-induced G6p and Pepck expression in primary cultures of mouse hepatocyes and kidney LLC-PK1-FBPase(+) cells. |
| 101 | 11696581 | 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. |
| 102 | 11696581 | The forkhead transcription factor Foxo1 (Fkhr) confers insulin sensitivity onto glucose-6-phosphatase expression. |
| 103 | 11696581 | The latter result in transcriptional suppression of key gluconeogenetic and glycogenolytic enzymes, phosphoenolpyruvate carboxykinase (Pepck) and glucose-6-phosphatase (G6p). |
| 104 | 11696581 | The inability to respond to insulin is associated with reduced expression of the forkhead transcription factor Foxo1, a substrate of the Akt kinase that is inhibited by insulin through phosphorylation. |
| 105 | 11696581 | Transduction of kidney cells with recombinant adenovirus encoding Foxo1 results in insulin inhibition of dex/cAMP-induced G6p expression. |
| 106 | 11696581 | Moreover, expression of dominant negative Foxo1 mutant results in partial inhibition of dex/cAMP-induced G6p and Pepck expression in primary cultures of mouse hepatocyes and kidney LLC-PK1-FBPase(+) cells. |
| 107 | 11696581 | 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. |
| 108 | 11696581 | The forkhead transcription factor Foxo1 (Fkhr) confers insulin sensitivity onto glucose-6-phosphatase expression. |
| 109 | 11696581 | The latter result in transcriptional suppression of key gluconeogenetic and glycogenolytic enzymes, phosphoenolpyruvate carboxykinase (Pepck) and glucose-6-phosphatase (G6p). |
| 110 | 11696581 | The inability to respond to insulin is associated with reduced expression of the forkhead transcription factor Foxo1, a substrate of the Akt kinase that is inhibited by insulin through phosphorylation. |
| 111 | 11696581 | Transduction of kidney cells with recombinant adenovirus encoding Foxo1 results in insulin inhibition of dex/cAMP-induced G6p expression. |
| 112 | 11696581 | Moreover, expression of dominant negative Foxo1 mutant results in partial inhibition of dex/cAMP-induced G6p and Pepck expression in primary cultures of mouse hepatocyes and kidney LLC-PK1-FBPase(+) cells. |
| 113 | 11696581 | 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. |
| 114 | 11696581 | The forkhead transcription factor Foxo1 (Fkhr) confers insulin sensitivity onto glucose-6-phosphatase expression. |
| 115 | 11696581 | The latter result in transcriptional suppression of key gluconeogenetic and glycogenolytic enzymes, phosphoenolpyruvate carboxykinase (Pepck) and glucose-6-phosphatase (G6p). |
| 116 | 11696581 | The inability to respond to insulin is associated with reduced expression of the forkhead transcription factor Foxo1, a substrate of the Akt kinase that is inhibited by insulin through phosphorylation. |
| 117 | 11696581 | Transduction of kidney cells with recombinant adenovirus encoding Foxo1 results in insulin inhibition of dex/cAMP-induced G6p expression. |
| 118 | 11696581 | Moreover, expression of dominant negative Foxo1 mutant results in partial inhibition of dex/cAMP-induced G6p and Pepck expression in primary cultures of mouse hepatocyes and kidney LLC-PK1-FBPase(+) cells. |
| 119 | 11696581 | 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. |
| 120 | 11696581 | The forkhead transcription factor Foxo1 (Fkhr) confers insulin sensitivity onto glucose-6-phosphatase expression. |
| 121 | 11696581 | The latter result in transcriptional suppression of key gluconeogenetic and glycogenolytic enzymes, phosphoenolpyruvate carboxykinase (Pepck) and glucose-6-phosphatase (G6p). |
| 122 | 11696581 | The inability to respond to insulin is associated with reduced expression of the forkhead transcription factor Foxo1, a substrate of the Akt kinase that is inhibited by insulin through phosphorylation. |
| 123 | 11696581 | Transduction of kidney cells with recombinant adenovirus encoding Foxo1 results in insulin inhibition of dex/cAMP-induced G6p expression. |
| 124 | 11696581 | Moreover, expression of dominant negative Foxo1 mutant results in partial inhibition of dex/cAMP-induced G6p and Pepck expression in primary cultures of mouse hepatocyes and kidney LLC-PK1-FBPase(+) cells. |
| 125 | 11696581 | 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. |
| 126 | 11919188 | A Forkhead/winged helix-related transcription factor mediates insulin-increased plasminogen activator inhibitor-1 gene transcription. |
| 127 | 11919188 | Insulin increases PAI-1 production in several experimental systems, but the mechanism of insulin-activated PAI-1 transcription remains to be determined. |
| 128 | 11919188 | Deletion analysis of the PAI-1 promoter revealed that the insulin response element is between -117 and -7. |
| 129 | 11919188 | Mutation of the AT-rich site at -52/-45 abolished the insulin responsiveness of the PAI-1 promoter. |
| 130 | 11919188 | Gel-mobility shift assays demonstrated that the forkhead bound to the PAI-1 promoter insulin response element. |
| 131 | 11919188 | Expression of the DNA-binding domain of FKHR acted as a dominant negative to block insulin-increased PAI-1-CAT expression. |
| 132 | 11919188 | These data suggested that a member of the Forkhead/winged helix family of transcription factors mediated the effect of insulin on PAI-1 transcription. |
| 133 | 11919188 | Inhibition of phosphatidylinositol 3-kinase reduced the effect of insulin on PAI-1 gene expression, a result consistent with activation through FKHR. |
| 134 | 11919188 | However, it was likely that a different member of the FKHR family (not FKHR) mediated this effect since FKHR was present in both insulin-responsive and non-responsive cell lines. |
| 135 | 11919188 | A Forkhead/winged helix-related transcription factor mediates insulin-increased plasminogen activator inhibitor-1 gene transcription. |
| 136 | 11919188 | Insulin increases PAI-1 production in several experimental systems, but the mechanism of insulin-activated PAI-1 transcription remains to be determined. |
| 137 | 11919188 | Deletion analysis of the PAI-1 promoter revealed that the insulin response element is between -117 and -7. |
| 138 | 11919188 | Mutation of the AT-rich site at -52/-45 abolished the insulin responsiveness of the PAI-1 promoter. |
| 139 | 11919188 | Gel-mobility shift assays demonstrated that the forkhead bound to the PAI-1 promoter insulin response element. |
| 140 | 11919188 | Expression of the DNA-binding domain of FKHR acted as a dominant negative to block insulin-increased PAI-1-CAT expression. |
| 141 | 11919188 | These data suggested that a member of the Forkhead/winged helix family of transcription factors mediated the effect of insulin on PAI-1 transcription. |
| 142 | 11919188 | Inhibition of phosphatidylinositol 3-kinase reduced the effect of insulin on PAI-1 gene expression, a result consistent with activation through FKHR. |
| 143 | 11919188 | However, it was likely that a different member of the FKHR family (not FKHR) mediated this effect since FKHR was present in both insulin-responsive and non-responsive cell lines. |
| 144 | 11919188 | A Forkhead/winged helix-related transcription factor mediates insulin-increased plasminogen activator inhibitor-1 gene transcription. |
| 145 | 11919188 | Insulin increases PAI-1 production in several experimental systems, but the mechanism of insulin-activated PAI-1 transcription remains to be determined. |
| 146 | 11919188 | Deletion analysis of the PAI-1 promoter revealed that the insulin response element is between -117 and -7. |
| 147 | 11919188 | Mutation of the AT-rich site at -52/-45 abolished the insulin responsiveness of the PAI-1 promoter. |
| 148 | 11919188 | Gel-mobility shift assays demonstrated that the forkhead bound to the PAI-1 promoter insulin response element. |
| 149 | 11919188 | Expression of the DNA-binding domain of FKHR acted as a dominant negative to block insulin-increased PAI-1-CAT expression. |
| 150 | 11919188 | These data suggested that a member of the Forkhead/winged helix family of transcription factors mediated the effect of insulin on PAI-1 transcription. |
| 151 | 11919188 | Inhibition of phosphatidylinositol 3-kinase reduced the effect of insulin on PAI-1 gene expression, a result consistent with activation through FKHR. |
| 152 | 11919188 | However, it was likely that a different member of the FKHR family (not FKHR) mediated this effect since FKHR was present in both insulin-responsive and non-responsive cell lines. |
| 153 | 12082100 | Differential roles of insulin receptor substrates in the anti-apoptotic function of insulin-like growth factor-1 and insulin. |
| 154 | 12082100 | Insulin-like growth factor-1 (IGF-1) and insulin are known to prevent apoptosis. |
| 155 | 12082100 | The signaling network of IGF-1 and insulin occurs via multiple pathways involving different insulin receptor substrates (IRSs). |
| 156 | 12082100 | To define their roles in the anti-apoptotic function of IGF-1 and insulin, we established brown pre-adipocyte cell lines from wild-type and IRS knockout (KO) animals. |
| 157 | 12082100 | In response to 16 h of serum deprivation, IRS-1-deficient cells showed a significant decrease in response to IGF-1 protection from apoptosis, whereas no changes were observed in the IRS-2, IRS-3, or IRS-4 KO cells. |
| 158 | 12082100 | At this early time point, IGF-1 and insulin were able to protect both wild-type and IRS-1 KO cells from death by 85-90%. |
| 159 | 12082100 | After a longer period of serum deprivation, the protective ability of insulin and IGF-1 was decreased, and this was especially reduced in the IRS-1 KO cells. |
| 160 | 12082100 | Reconstitution of these cells with IRS-1, IRS-2, IRS-3, or IRS-1/IRS-2 chimeras restored the anti-apoptotic effects of IGF-1, whereas overexpression of IRS-4 had no effect at long time points and actually reduced the effect of IGF-1 at the short time point. |
| 161 | 12082100 | Phosphorylation of the transcription factors cAMP response element-binding protein and FKHR by IGF-1 and insulin was markedly reduced in IRS-1 KO cells. |
| 162 | 12082100 | In addition, both IGF-1 and insulin prevented caspase-3 cleavage in the wild-type cells, and this effect was greatly reduced in the IRS-1-deficient cells. |
| 163 | 12082100 | These findings suggest that the IRS proteins may play differential roles in the anti-apoptotic effects of IGF-1 and insulin in brown pre-adipocytes, with IRS-1 being predominant, possibly acting through caspase-3-, CREB-, and FKHR-dependent mechanisms. |
| 164 | 12082100 | Differential roles of insulin receptor substrates in the anti-apoptotic function of insulin-like growth factor-1 and insulin. |
| 165 | 12082100 | Insulin-like growth factor-1 (IGF-1) and insulin are known to prevent apoptosis. |
| 166 | 12082100 | The signaling network of IGF-1 and insulin occurs via multiple pathways involving different insulin receptor substrates (IRSs). |
| 167 | 12082100 | To define their roles in the anti-apoptotic function of IGF-1 and insulin, we established brown pre-adipocyte cell lines from wild-type and IRS knockout (KO) animals. |
| 168 | 12082100 | In response to 16 h of serum deprivation, IRS-1-deficient cells showed a significant decrease in response to IGF-1 protection from apoptosis, whereas no changes were observed in the IRS-2, IRS-3, or IRS-4 KO cells. |
| 169 | 12082100 | At this early time point, IGF-1 and insulin were able to protect both wild-type and IRS-1 KO cells from death by 85-90%. |
| 170 | 12082100 | After a longer period of serum deprivation, the protective ability of insulin and IGF-1 was decreased, and this was especially reduced in the IRS-1 KO cells. |
| 171 | 12082100 | Reconstitution of these cells with IRS-1, IRS-2, IRS-3, or IRS-1/IRS-2 chimeras restored the anti-apoptotic effects of IGF-1, whereas overexpression of IRS-4 had no effect at long time points and actually reduced the effect of IGF-1 at the short time point. |
| 172 | 12082100 | Phosphorylation of the transcription factors cAMP response element-binding protein and FKHR by IGF-1 and insulin was markedly reduced in IRS-1 KO cells. |
| 173 | 12082100 | In addition, both IGF-1 and insulin prevented caspase-3 cleavage in the wild-type cells, and this effect was greatly reduced in the IRS-1-deficient cells. |
| 174 | 12082100 | These findings suggest that the IRS proteins may play differential roles in the anti-apoptotic effects of IGF-1 and insulin in brown pre-adipocytes, with IRS-1 being predominant, possibly acting through caspase-3-, CREB-, and FKHR-dependent mechanisms. |
| 175 | 12219087 | Regulation of insulin action and pancreatic beta-cell function by mutated alleles of the gene encoding forkhead transcription factor Foxo1. |
| 176 | 12219087 | We show that haploinsufficiency of the Foxo1 gene, encoding a forkhead transcription factor (forkhead box transcription factor O1), restores insulin sensitivity and rescues the diabetic phenotype in insulin-resistant mice by reducing hepatic expression of glucogenetic genes and increasing adipocyte expression of insulin-sensitizing genes. |
| 177 | 12219087 | Conversely, a gain-of-function Foxo1 mutation targeted to liver and pancreatic beta-cells results in diabetes arising from a combination of increased hepatic glucose production and impaired beta-cell compensation due to decreased Pdx1 expression. |
| 178 | 12219087 | These data indicate that Foxo1 is a negative regulator of insulin sensitivity in liver, adipocytes and pancreatic beta-cells. |
| 179 | 12219087 | Impaired insulin signaling to Foxo1 provides a unifying mechanism for the common metabolic abnormalities of type 2 diabetes.NOTE: In the AOP version of this article, the name of the fourth author was misspelled as W K Cavanee rather than the correct spelling: W K Cavenee. |
| 180 | 12219087 | Regulation of insulin action and pancreatic beta-cell function by mutated alleles of the gene encoding forkhead transcription factor Foxo1. |
| 181 | 12219087 | We show that haploinsufficiency of the Foxo1 gene, encoding a forkhead transcription factor (forkhead box transcription factor O1), restores insulin sensitivity and rescues the diabetic phenotype in insulin-resistant mice by reducing hepatic expression of glucogenetic genes and increasing adipocyte expression of insulin-sensitizing genes. |
| 182 | 12219087 | Conversely, a gain-of-function Foxo1 mutation targeted to liver and pancreatic beta-cells results in diabetes arising from a combination of increased hepatic glucose production and impaired beta-cell compensation due to decreased Pdx1 expression. |
| 183 | 12219087 | These data indicate that Foxo1 is a negative regulator of insulin sensitivity in liver, adipocytes and pancreatic beta-cells. |
| 184 | 12219087 | Impaired insulin signaling to Foxo1 provides a unifying mechanism for the common metabolic abnormalities of type 2 diabetes.NOTE: In the AOP version of this article, the name of the fourth author was misspelled as W K Cavanee rather than the correct spelling: W K Cavenee. |
| 185 | 12219087 | Regulation of insulin action and pancreatic beta-cell function by mutated alleles of the gene encoding forkhead transcription factor Foxo1. |
| 186 | 12219087 | We show that haploinsufficiency of the Foxo1 gene, encoding a forkhead transcription factor (forkhead box transcription factor O1), restores insulin sensitivity and rescues the diabetic phenotype in insulin-resistant mice by reducing hepatic expression of glucogenetic genes and increasing adipocyte expression of insulin-sensitizing genes. |
| 187 | 12219087 | Conversely, a gain-of-function Foxo1 mutation targeted to liver and pancreatic beta-cells results in diabetes arising from a combination of increased hepatic glucose production and impaired beta-cell compensation due to decreased Pdx1 expression. |
| 188 | 12219087 | These data indicate that Foxo1 is a negative regulator of insulin sensitivity in liver, adipocytes and pancreatic beta-cells. |
| 189 | 12219087 | Impaired insulin signaling to Foxo1 provides a unifying mechanism for the common metabolic abnormalities of type 2 diabetes.NOTE: In the AOP version of this article, the name of the fourth author was misspelled as W K Cavanee rather than the correct spelling: W K Cavenee. |
| 190 | 12219087 | Regulation of insulin action and pancreatic beta-cell function by mutated alleles of the gene encoding forkhead transcription factor Foxo1. |
| 191 | 12219087 | We show that haploinsufficiency of the Foxo1 gene, encoding a forkhead transcription factor (forkhead box transcription factor O1), restores insulin sensitivity and rescues the diabetic phenotype in insulin-resistant mice by reducing hepatic expression of glucogenetic genes and increasing adipocyte expression of insulin-sensitizing genes. |
| 192 | 12219087 | Conversely, a gain-of-function Foxo1 mutation targeted to liver and pancreatic beta-cells results in diabetes arising from a combination of increased hepatic glucose production and impaired beta-cell compensation due to decreased Pdx1 expression. |
| 193 | 12219087 | These data indicate that Foxo1 is a negative regulator of insulin sensitivity in liver, adipocytes and pancreatic beta-cells. |
| 194 | 12219087 | Impaired insulin signaling to Foxo1 provides a unifying mechanism for the common metabolic abnormalities of type 2 diabetes.NOTE: In the AOP version of this article, the name of the fourth author was misspelled as W K Cavanee rather than the correct spelling: W K Cavenee. |
| 195 | 12219087 | Regulation of insulin action and pancreatic beta-cell function by mutated alleles of the gene encoding forkhead transcription factor Foxo1. |
| 196 | 12219087 | We show that haploinsufficiency of the Foxo1 gene, encoding a forkhead transcription factor (forkhead box transcription factor O1), restores insulin sensitivity and rescues the diabetic phenotype in insulin-resistant mice by reducing hepatic expression of glucogenetic genes and increasing adipocyte expression of insulin-sensitizing genes. |
| 197 | 12219087 | Conversely, a gain-of-function Foxo1 mutation targeted to liver and pancreatic beta-cells results in diabetes arising from a combination of increased hepatic glucose production and impaired beta-cell compensation due to decreased Pdx1 expression. |
| 198 | 12219087 | These data indicate that Foxo1 is a negative regulator of insulin sensitivity in liver, adipocytes and pancreatic beta-cells. |
| 199 | 12219087 | Impaired insulin signaling to Foxo1 provides a unifying mechanism for the common metabolic abnormalities of type 2 diabetes.NOTE: In the AOP version of this article, the name of the fourth author was misspelled as W K Cavanee rather than the correct spelling: W K Cavenee. |
| 200 | 12373635 | Construction and characterization of a conditionally active construct of the insulin-regulated forkhead transcription factor FKHR. |
| 201 | 12373635 | Insulin is known to inhibit glucose-6-phosphatase gene expression through PI 3-kinase/PKB mediated phosphorylation and inactivation of the forkhead transcription factor FKHR, which is a potent transactivator of the glucose-6-phosphatase gene. |
| 202 | 12373635 | Abbreviations used: FKHR, forkhead in rhabdomyosarcoma; G6Pase, glucose-6-phosphatase; PKB, protein kinase B; PI 3-kinase, phosphatidyl-inositol 3-kinase; IRU, insulin-responsive unit; Tx, 4-hydroxytamoxifen, ER, estrogen receptor; HBD, hormone binding domain |
| 203 | 12373635 | Construction and characterization of a conditionally active construct of the insulin-regulated forkhead transcription factor FKHR. |
| 204 | 12373635 | Insulin is known to inhibit glucose-6-phosphatase gene expression through PI 3-kinase/PKB mediated phosphorylation and inactivation of the forkhead transcription factor FKHR, which is a potent transactivator of the glucose-6-phosphatase gene. |
| 205 | 12373635 | Abbreviations used: FKHR, forkhead in rhabdomyosarcoma; G6Pase, glucose-6-phosphatase; PKB, protein kinase B; PI 3-kinase, phosphatidyl-inositol 3-kinase; IRU, insulin-responsive unit; Tx, 4-hydroxytamoxifen, ER, estrogen receptor; HBD, hormone binding domain |
| 206 | 12373635 | Construction and characterization of a conditionally active construct of the insulin-regulated forkhead transcription factor FKHR. |
| 207 | 12373635 | Insulin is known to inhibit glucose-6-phosphatase gene expression through PI 3-kinase/PKB mediated phosphorylation and inactivation of the forkhead transcription factor FKHR, which is a potent transactivator of the glucose-6-phosphatase gene. |
| 208 | 12373635 | Abbreviations used: FKHR, forkhead in rhabdomyosarcoma; G6Pase, glucose-6-phosphatase; PKB, protein kinase B; PI 3-kinase, phosphatidyl-inositol 3-kinase; IRU, insulin-responsive unit; Tx, 4-hydroxytamoxifen, ER, estrogen receptor; HBD, hormone binding domain |
| 209 | 12414908 | PAX3/forkhead homolog in rhabdomyosarcoma oncoprotein activates glucose transporter 4 gene expression in vivo and in vitro. |
| 210 | 12414908 | In the muscle-derived tumor alveolar rhabdomyosarcoma (ARMS), a chromosomal translocation t(2:13) generates the PAX3/forkhead homolog in rhabdomyosarcoma (FKHR) oncoprotein. |
| 211 | 12414908 | Therefore, we evaluated the role of PAX3/FKHR in the regulation of GLUT4 gene expression in muscle tumorigenesis. |
| 212 | 12414908 | GLUT4 mRNA and protein were detected in ARMS-derived human biopsies and in ARMS-derived RH30 myoblasts, which both express the PAX3/FKHR chimeric protein, but not in either C2C12 or embryonal rhabdomyosarcoma-derived myoblasts. |
| 213 | 12414908 | GLUT4 was functionally active in RH30 cells, because insulin induced a 1.4-fold stimulation of basal 2-deoxyglucose uptake rates. |
| 214 | 12414908 | Coexpression of PAX3/FKHR increased basal transcriptional activity from a GLUT4 promoter reporter (GLUT4-P) in C2C12, SaOS-2, and Chinese hamster ovary-K1 cells in a dose-dependent and tissue-specific manner. |
| 215 | 12414908 | PAX3/FKHR mutants with deletions in either the homeodomain (DeltaHD) or the FKHR-derived activation domain (DeltaFKHR), or in which the PAX3-derived paired domain (PD) was point-mutated (PD-R56L), were unable to activate GLUT4-P. |
| 216 | 12414908 | EMSA studies established that the PAX3/FKHR protein directly and specifically binds to this region and to a shorter fragment, -4/+36 bp, that contains potential binding sites for HD and PD, but not to a -4/+36-bp fragment whose HD and PD sites have been mutated. |
| 217 | 12414908 | Thus, the functional interaction of PAX3/FKHR with GLUT4-P appears to require all of the functional domains of PAX3/FKHR, as well as a -4/+36-bp region within the GLUT4 promoter. |
| 218 | 12414908 | Taken together, the data suggest that the GLUT4 gene is a downstream target of PAX3/FKHR and that GLUT4 is aberrantly transactivated by this oncoprotein both in vivo and in vitro. |
| 219 | 12414908 | PAX3/forkhead homolog in rhabdomyosarcoma oncoprotein activates glucose transporter 4 gene expression in vivo and in vitro. |
| 220 | 12414908 | In the muscle-derived tumor alveolar rhabdomyosarcoma (ARMS), a chromosomal translocation t(2:13) generates the PAX3/forkhead homolog in rhabdomyosarcoma (FKHR) oncoprotein. |
| 221 | 12414908 | Therefore, we evaluated the role of PAX3/FKHR in the regulation of GLUT4 gene expression in muscle tumorigenesis. |
| 222 | 12414908 | GLUT4 mRNA and protein were detected in ARMS-derived human biopsies and in ARMS-derived RH30 myoblasts, which both express the PAX3/FKHR chimeric protein, but not in either C2C12 or embryonal rhabdomyosarcoma-derived myoblasts. |
| 223 | 12414908 | GLUT4 was functionally active in RH30 cells, because insulin induced a 1.4-fold stimulation of basal 2-deoxyglucose uptake rates. |
| 224 | 12414908 | Coexpression of PAX3/FKHR increased basal transcriptional activity from a GLUT4 promoter reporter (GLUT4-P) in C2C12, SaOS-2, and Chinese hamster ovary-K1 cells in a dose-dependent and tissue-specific manner. |
| 225 | 12414908 | PAX3/FKHR mutants with deletions in either the homeodomain (DeltaHD) or the FKHR-derived activation domain (DeltaFKHR), or in which the PAX3-derived paired domain (PD) was point-mutated (PD-R56L), were unable to activate GLUT4-P. |
| 226 | 12414908 | EMSA studies established that the PAX3/FKHR protein directly and specifically binds to this region and to a shorter fragment, -4/+36 bp, that contains potential binding sites for HD and PD, but not to a -4/+36-bp fragment whose HD and PD sites have been mutated. |
| 227 | 12414908 | Thus, the functional interaction of PAX3/FKHR with GLUT4-P appears to require all of the functional domains of PAX3/FKHR, as well as a -4/+36-bp region within the GLUT4 promoter. |
| 228 | 12414908 | Taken together, the data suggest that the GLUT4 gene is a downstream target of PAX3/FKHR and that GLUT4 is aberrantly transactivated by this oncoprotein both in vivo and in vitro. |
| 229 | 12414908 | PAX3/forkhead homolog in rhabdomyosarcoma oncoprotein activates glucose transporter 4 gene expression in vivo and in vitro. |
| 230 | 12414908 | In the muscle-derived tumor alveolar rhabdomyosarcoma (ARMS), a chromosomal translocation t(2:13) generates the PAX3/forkhead homolog in rhabdomyosarcoma (FKHR) oncoprotein. |
| 231 | 12414908 | Therefore, we evaluated the role of PAX3/FKHR in the regulation of GLUT4 gene expression in muscle tumorigenesis. |
| 232 | 12414908 | GLUT4 mRNA and protein were detected in ARMS-derived human biopsies and in ARMS-derived RH30 myoblasts, which both express the PAX3/FKHR chimeric protein, but not in either C2C12 or embryonal rhabdomyosarcoma-derived myoblasts. |
| 233 | 12414908 | GLUT4 was functionally active in RH30 cells, because insulin induced a 1.4-fold stimulation of basal 2-deoxyglucose uptake rates. |
| 234 | 12414908 | Coexpression of PAX3/FKHR increased basal transcriptional activity from a GLUT4 promoter reporter (GLUT4-P) in C2C12, SaOS-2, and Chinese hamster ovary-K1 cells in a dose-dependent and tissue-specific manner. |
| 235 | 12414908 | PAX3/FKHR mutants with deletions in either the homeodomain (DeltaHD) or the FKHR-derived activation domain (DeltaFKHR), or in which the PAX3-derived paired domain (PD) was point-mutated (PD-R56L), were unable to activate GLUT4-P. |
| 236 | 12414908 | EMSA studies established that the PAX3/FKHR protein directly and specifically binds to this region and to a shorter fragment, -4/+36 bp, that contains potential binding sites for HD and PD, but not to a -4/+36-bp fragment whose HD and PD sites have been mutated. |
| 237 | 12414908 | Thus, the functional interaction of PAX3/FKHR with GLUT4-P appears to require all of the functional domains of PAX3/FKHR, as well as a -4/+36-bp region within the GLUT4 promoter. |
| 238 | 12414908 | Taken together, the data suggest that the GLUT4 gene is a downstream target of PAX3/FKHR and that GLUT4 is aberrantly transactivated by this oncoprotein both in vivo and in vitro. |
| 239 | 12414908 | PAX3/forkhead homolog in rhabdomyosarcoma oncoprotein activates glucose transporter 4 gene expression in vivo and in vitro. |
| 240 | 12414908 | In the muscle-derived tumor alveolar rhabdomyosarcoma (ARMS), a chromosomal translocation t(2:13) generates the PAX3/forkhead homolog in rhabdomyosarcoma (FKHR) oncoprotein. |
| 241 | 12414908 | Therefore, we evaluated the role of PAX3/FKHR in the regulation of GLUT4 gene expression in muscle tumorigenesis. |
| 242 | 12414908 | GLUT4 mRNA and protein were detected in ARMS-derived human biopsies and in ARMS-derived RH30 myoblasts, which both express the PAX3/FKHR chimeric protein, but not in either C2C12 or embryonal rhabdomyosarcoma-derived myoblasts. |
| 243 | 12414908 | GLUT4 was functionally active in RH30 cells, because insulin induced a 1.4-fold stimulation of basal 2-deoxyglucose uptake rates. |
| 244 | 12414908 | Coexpression of PAX3/FKHR increased basal transcriptional activity from a GLUT4 promoter reporter (GLUT4-P) in C2C12, SaOS-2, and Chinese hamster ovary-K1 cells in a dose-dependent and tissue-specific manner. |
| 245 | 12414908 | PAX3/FKHR mutants with deletions in either the homeodomain (DeltaHD) or the FKHR-derived activation domain (DeltaFKHR), or in which the PAX3-derived paired domain (PD) was point-mutated (PD-R56L), were unable to activate GLUT4-P. |
| 246 | 12414908 | EMSA studies established that the PAX3/FKHR protein directly and specifically binds to this region and to a shorter fragment, -4/+36 bp, that contains potential binding sites for HD and PD, but not to a -4/+36-bp fragment whose HD and PD sites have been mutated. |
| 247 | 12414908 | Thus, the functional interaction of PAX3/FKHR with GLUT4-P appears to require all of the functional domains of PAX3/FKHR, as well as a -4/+36-bp region within the GLUT4 promoter. |
| 248 | 12414908 | Taken together, the data suggest that the GLUT4 gene is a downstream target of PAX3/FKHR and that GLUT4 is aberrantly transactivated by this oncoprotein both in vivo and in vitro. |
| 249 | 12414908 | PAX3/forkhead homolog in rhabdomyosarcoma oncoprotein activates glucose transporter 4 gene expression in vivo and in vitro. |
| 250 | 12414908 | In the muscle-derived tumor alveolar rhabdomyosarcoma (ARMS), a chromosomal translocation t(2:13) generates the PAX3/forkhead homolog in rhabdomyosarcoma (FKHR) oncoprotein. |
| 251 | 12414908 | Therefore, we evaluated the role of PAX3/FKHR in the regulation of GLUT4 gene expression in muscle tumorigenesis. |
| 252 | 12414908 | GLUT4 mRNA and protein were detected in ARMS-derived human biopsies and in ARMS-derived RH30 myoblasts, which both express the PAX3/FKHR chimeric protein, but not in either C2C12 or embryonal rhabdomyosarcoma-derived myoblasts. |
| 253 | 12414908 | GLUT4 was functionally active in RH30 cells, because insulin induced a 1.4-fold stimulation of basal 2-deoxyglucose uptake rates. |
| 254 | 12414908 | Coexpression of PAX3/FKHR increased basal transcriptional activity from a GLUT4 promoter reporter (GLUT4-P) in C2C12, SaOS-2, and Chinese hamster ovary-K1 cells in a dose-dependent and tissue-specific manner. |
| 255 | 12414908 | PAX3/FKHR mutants with deletions in either the homeodomain (DeltaHD) or the FKHR-derived activation domain (DeltaFKHR), or in which the PAX3-derived paired domain (PD) was point-mutated (PD-R56L), were unable to activate GLUT4-P. |
| 256 | 12414908 | EMSA studies established that the PAX3/FKHR protein directly and specifically binds to this region and to a shorter fragment, -4/+36 bp, that contains potential binding sites for HD and PD, but not to a -4/+36-bp fragment whose HD and PD sites have been mutated. |
| 257 | 12414908 | Thus, the functional interaction of PAX3/FKHR with GLUT4-P appears to require all of the functional domains of PAX3/FKHR, as well as a -4/+36-bp region within the GLUT4 promoter. |
| 258 | 12414908 | Taken together, the data suggest that the GLUT4 gene is a downstream target of PAX3/FKHR and that GLUT4 is aberrantly transactivated by this oncoprotein both in vivo and in vitro. |
| 259 | 12414908 | PAX3/forkhead homolog in rhabdomyosarcoma oncoprotein activates glucose transporter 4 gene expression in vivo and in vitro. |
| 260 | 12414908 | In the muscle-derived tumor alveolar rhabdomyosarcoma (ARMS), a chromosomal translocation t(2:13) generates the PAX3/forkhead homolog in rhabdomyosarcoma (FKHR) oncoprotein. |
| 261 | 12414908 | Therefore, we evaluated the role of PAX3/FKHR in the regulation of GLUT4 gene expression in muscle tumorigenesis. |
| 262 | 12414908 | GLUT4 mRNA and protein were detected in ARMS-derived human biopsies and in ARMS-derived RH30 myoblasts, which both express the PAX3/FKHR chimeric protein, but not in either C2C12 or embryonal rhabdomyosarcoma-derived myoblasts. |
| 263 | 12414908 | GLUT4 was functionally active in RH30 cells, because insulin induced a 1.4-fold stimulation of basal 2-deoxyglucose uptake rates. |
| 264 | 12414908 | Coexpression of PAX3/FKHR increased basal transcriptional activity from a GLUT4 promoter reporter (GLUT4-P) in C2C12, SaOS-2, and Chinese hamster ovary-K1 cells in a dose-dependent and tissue-specific manner. |
| 265 | 12414908 | PAX3/FKHR mutants with deletions in either the homeodomain (DeltaHD) or the FKHR-derived activation domain (DeltaFKHR), or in which the PAX3-derived paired domain (PD) was point-mutated (PD-R56L), were unable to activate GLUT4-P. |
| 266 | 12414908 | EMSA studies established that the PAX3/FKHR protein directly and specifically binds to this region and to a shorter fragment, -4/+36 bp, that contains potential binding sites for HD and PD, but not to a -4/+36-bp fragment whose HD and PD sites have been mutated. |
| 267 | 12414908 | Thus, the functional interaction of PAX3/FKHR with GLUT4-P appears to require all of the functional domains of PAX3/FKHR, as well as a -4/+36-bp region within the GLUT4 promoter. |
| 268 | 12414908 | Taken together, the data suggest that the GLUT4 gene is a downstream target of PAX3/FKHR and that GLUT4 is aberrantly transactivated by this oncoprotein both in vivo and in vitro. |
| 269 | 12414908 | PAX3/forkhead homolog in rhabdomyosarcoma oncoprotein activates glucose transporter 4 gene expression in vivo and in vitro. |
| 270 | 12414908 | In the muscle-derived tumor alveolar rhabdomyosarcoma (ARMS), a chromosomal translocation t(2:13) generates the PAX3/forkhead homolog in rhabdomyosarcoma (FKHR) oncoprotein. |
| 271 | 12414908 | Therefore, we evaluated the role of PAX3/FKHR in the regulation of GLUT4 gene expression in muscle tumorigenesis. |
| 272 | 12414908 | GLUT4 mRNA and protein were detected in ARMS-derived human biopsies and in ARMS-derived RH30 myoblasts, which both express the PAX3/FKHR chimeric protein, but not in either C2C12 or embryonal rhabdomyosarcoma-derived myoblasts. |
| 273 | 12414908 | GLUT4 was functionally active in RH30 cells, because insulin induced a 1.4-fold stimulation of basal 2-deoxyglucose uptake rates. |
| 274 | 12414908 | Coexpression of PAX3/FKHR increased basal transcriptional activity from a GLUT4 promoter reporter (GLUT4-P) in C2C12, SaOS-2, and Chinese hamster ovary-K1 cells in a dose-dependent and tissue-specific manner. |
| 275 | 12414908 | PAX3/FKHR mutants with deletions in either the homeodomain (DeltaHD) or the FKHR-derived activation domain (DeltaFKHR), or in which the PAX3-derived paired domain (PD) was point-mutated (PD-R56L), were unable to activate GLUT4-P. |
| 276 | 12414908 | EMSA studies established that the PAX3/FKHR protein directly and specifically binds to this region and to a shorter fragment, -4/+36 bp, that contains potential binding sites for HD and PD, but not to a -4/+36-bp fragment whose HD and PD sites have been mutated. |
| 277 | 12414908 | Thus, the functional interaction of PAX3/FKHR with GLUT4-P appears to require all of the functional domains of PAX3/FKHR, as well as a -4/+36-bp region within the GLUT4 promoter. |
| 278 | 12414908 | Taken together, the data suggest that the GLUT4 gene is a downstream target of PAX3/FKHR and that GLUT4 is aberrantly transactivated by this oncoprotein both in vivo and in vitro. |
| 279 | 12414908 | PAX3/forkhead homolog in rhabdomyosarcoma oncoprotein activates glucose transporter 4 gene expression in vivo and in vitro. |
| 280 | 12414908 | In the muscle-derived tumor alveolar rhabdomyosarcoma (ARMS), a chromosomal translocation t(2:13) generates the PAX3/forkhead homolog in rhabdomyosarcoma (FKHR) oncoprotein. |
| 281 | 12414908 | Therefore, we evaluated the role of PAX3/FKHR in the regulation of GLUT4 gene expression in muscle tumorigenesis. |
| 282 | 12414908 | GLUT4 mRNA and protein were detected in ARMS-derived human biopsies and in ARMS-derived RH30 myoblasts, which both express the PAX3/FKHR chimeric protein, but not in either C2C12 or embryonal rhabdomyosarcoma-derived myoblasts. |
| 283 | 12414908 | GLUT4 was functionally active in RH30 cells, because insulin induced a 1.4-fold stimulation of basal 2-deoxyglucose uptake rates. |
| 284 | 12414908 | Coexpression of PAX3/FKHR increased basal transcriptional activity from a GLUT4 promoter reporter (GLUT4-P) in C2C12, SaOS-2, and Chinese hamster ovary-K1 cells in a dose-dependent and tissue-specific manner. |
| 285 | 12414908 | PAX3/FKHR mutants with deletions in either the homeodomain (DeltaHD) or the FKHR-derived activation domain (DeltaFKHR), or in which the PAX3-derived paired domain (PD) was point-mutated (PD-R56L), were unable to activate GLUT4-P. |
| 286 | 12414908 | EMSA studies established that the PAX3/FKHR protein directly and specifically binds to this region and to a shorter fragment, -4/+36 bp, that contains potential binding sites for HD and PD, but not to a -4/+36-bp fragment whose HD and PD sites have been mutated. |
| 287 | 12414908 | Thus, the functional interaction of PAX3/FKHR with GLUT4-P appears to require all of the functional domains of PAX3/FKHR, as well as a -4/+36-bp region within the GLUT4 promoter. |
| 288 | 12414908 | Taken together, the data suggest that the GLUT4 gene is a downstream target of PAX3/FKHR and that GLUT4 is aberrantly transactivated by this oncoprotein both in vivo and in vitro. |
| 289 | 12414908 | PAX3/forkhead homolog in rhabdomyosarcoma oncoprotein activates glucose transporter 4 gene expression in vivo and in vitro. |
| 290 | 12414908 | In the muscle-derived tumor alveolar rhabdomyosarcoma (ARMS), a chromosomal translocation t(2:13) generates the PAX3/forkhead homolog in rhabdomyosarcoma (FKHR) oncoprotein. |
| 291 | 12414908 | Therefore, we evaluated the role of PAX3/FKHR in the regulation of GLUT4 gene expression in muscle tumorigenesis. |
| 292 | 12414908 | GLUT4 mRNA and protein were detected in ARMS-derived human biopsies and in ARMS-derived RH30 myoblasts, which both express the PAX3/FKHR chimeric protein, but not in either C2C12 or embryonal rhabdomyosarcoma-derived myoblasts. |
| 293 | 12414908 | GLUT4 was functionally active in RH30 cells, because insulin induced a 1.4-fold stimulation of basal 2-deoxyglucose uptake rates. |
| 294 | 12414908 | Coexpression of PAX3/FKHR increased basal transcriptional activity from a GLUT4 promoter reporter (GLUT4-P) in C2C12, SaOS-2, and Chinese hamster ovary-K1 cells in a dose-dependent and tissue-specific manner. |
| 295 | 12414908 | PAX3/FKHR mutants with deletions in either the homeodomain (DeltaHD) or the FKHR-derived activation domain (DeltaFKHR), or in which the PAX3-derived paired domain (PD) was point-mutated (PD-R56L), were unable to activate GLUT4-P. |
| 296 | 12414908 | EMSA studies established that the PAX3/FKHR protein directly and specifically binds to this region and to a shorter fragment, -4/+36 bp, that contains potential binding sites for HD and PD, but not to a -4/+36-bp fragment whose HD and PD sites have been mutated. |
| 297 | 12414908 | Thus, the functional interaction of PAX3/FKHR with GLUT4-P appears to require all of the functional domains of PAX3/FKHR, as well as a -4/+36-bp region within the GLUT4 promoter. |
| 298 | 12414908 | Taken together, the data suggest that the GLUT4 gene is a downstream target of PAX3/FKHR and that GLUT4 is aberrantly transactivated by this oncoprotein both in vivo and in vitro. |
| 299 | 12488434 | The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth. |
| 300 | 12488434 | We report that haploinsufficiency for the forkhead transcription factor Foxo1 reverses beta cell failure in Irs2(-/-) mice through partial restoration of beta cell proliferation and increased expression of the pancreatic transcription factor pancreas/duodenum homeobox gene-1 (Pdx1). |
| 301 | 12488434 | Foxo1 and Pdx1 exhibit mutually exclusive patterns of nuclear localization in beta cells, and constitutive nuclear expression of a mutant Foxo1 is associated with lack of Pdx1 expression. |
| 302 | 12488434 | We show that Foxo1 acts as a repressor of Foxa2-dependent (Hnf-3beta-dependent) expression from the Pdx1 promoter. |
| 303 | 12488434 | We propose that insulin/IGFs regulate beta cell proliferation by relieving Foxo1 inhibition of Pdx1 expression in a subset of cells embedded within pancreatic ducts. |
| 304 | 12488434 | The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth. |
| 305 | 12488434 | We report that haploinsufficiency for the forkhead transcription factor Foxo1 reverses beta cell failure in Irs2(-/-) mice through partial restoration of beta cell proliferation and increased expression of the pancreatic transcription factor pancreas/duodenum homeobox gene-1 (Pdx1). |
| 306 | 12488434 | Foxo1 and Pdx1 exhibit mutually exclusive patterns of nuclear localization in beta cells, and constitutive nuclear expression of a mutant Foxo1 is associated with lack of Pdx1 expression. |
| 307 | 12488434 | We show that Foxo1 acts as a repressor of Foxa2-dependent (Hnf-3beta-dependent) expression from the Pdx1 promoter. |
| 308 | 12488434 | We propose that insulin/IGFs regulate beta cell proliferation by relieving Foxo1 inhibition of Pdx1 expression in a subset of cells embedded within pancreatic ducts. |
| 309 | 12488434 | The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth. |
| 310 | 12488434 | We report that haploinsufficiency for the forkhead transcription factor Foxo1 reverses beta cell failure in Irs2(-/-) mice through partial restoration of beta cell proliferation and increased expression of the pancreatic transcription factor pancreas/duodenum homeobox gene-1 (Pdx1). |
| 311 | 12488434 | Foxo1 and Pdx1 exhibit mutually exclusive patterns of nuclear localization in beta cells, and constitutive nuclear expression of a mutant Foxo1 is associated with lack of Pdx1 expression. |
| 312 | 12488434 | We show that Foxo1 acts as a repressor of Foxa2-dependent (Hnf-3beta-dependent) expression from the Pdx1 promoter. |
| 313 | 12488434 | We propose that insulin/IGFs regulate beta cell proliferation by relieving Foxo1 inhibition of Pdx1 expression in a subset of cells embedded within pancreatic ducts. |
| 314 | 12488434 | The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth. |
| 315 | 12488434 | We report that haploinsufficiency for the forkhead transcription factor Foxo1 reverses beta cell failure in Irs2(-/-) mice through partial restoration of beta cell proliferation and increased expression of the pancreatic transcription factor pancreas/duodenum homeobox gene-1 (Pdx1). |
| 316 | 12488434 | Foxo1 and Pdx1 exhibit mutually exclusive patterns of nuclear localization in beta cells, and constitutive nuclear expression of a mutant Foxo1 is associated with lack of Pdx1 expression. |
| 317 | 12488434 | We show that Foxo1 acts as a repressor of Foxa2-dependent (Hnf-3beta-dependent) expression from the Pdx1 promoter. |
| 318 | 12488434 | We propose that insulin/IGFs regulate beta cell proliferation by relieving Foxo1 inhibition of Pdx1 expression in a subset of cells embedded within pancreatic ducts. |
| 319 | 12488434 | The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth. |
| 320 | 12488434 | We report that haploinsufficiency for the forkhead transcription factor Foxo1 reverses beta cell failure in Irs2(-/-) mice through partial restoration of beta cell proliferation and increased expression of the pancreatic transcription factor pancreas/duodenum homeobox gene-1 (Pdx1). |
| 321 | 12488434 | Foxo1 and Pdx1 exhibit mutually exclusive patterns of nuclear localization in beta cells, and constitutive nuclear expression of a mutant Foxo1 is associated with lack of Pdx1 expression. |
| 322 | 12488434 | We show that Foxo1 acts as a repressor of Foxa2-dependent (Hnf-3beta-dependent) expression from the Pdx1 promoter. |
| 323 | 12488434 | We propose that insulin/IGFs regulate beta cell proliferation by relieving Foxo1 inhibition of Pdx1 expression in a subset of cells embedded within pancreatic ducts. |
| 324 | 12530968 | The forkhead transcription factor Foxo1 regulates adipocyte differentiation. |
| 325 | 12530968 | The forkhead transcription factor Foxo1 is regulated by insulin via Akt-dependent phosphorylation and nuclear exclusion. |
| 326 | 12530968 | We show that Foxo1 is induced in the early stages of adipocyte differentiation but that its activation is delayed until the end of the clonal expansion phase. |
| 327 | 12530968 | Constitutively active Foxo1 prevents the differentiation of preadipocytes, while dominant-negative Foxo1 restores adipocyte differentiation of fibroblasts from insulin receptor-deficient mice. |
| 328 | 12530968 | We propose that Foxo1 plays an important role in the integration of hormone-activated signaling pathways with the complex transcriptional cascade that promotes adipocyte differentiation. |
| 329 | 12530968 | The forkhead transcription factor Foxo1 regulates adipocyte differentiation. |
| 330 | 12530968 | The forkhead transcription factor Foxo1 is regulated by insulin via Akt-dependent phosphorylation and nuclear exclusion. |
| 331 | 12530968 | We show that Foxo1 is induced in the early stages of adipocyte differentiation but that its activation is delayed until the end of the clonal expansion phase. |
| 332 | 12530968 | Constitutively active Foxo1 prevents the differentiation of preadipocytes, while dominant-negative Foxo1 restores adipocyte differentiation of fibroblasts from insulin receptor-deficient mice. |
| 333 | 12530968 | We propose that Foxo1 plays an important role in the integration of hormone-activated signaling pathways with the complex transcriptional cascade that promotes adipocyte differentiation. |
| 334 | 12530968 | The forkhead transcription factor Foxo1 regulates adipocyte differentiation. |
| 335 | 12530968 | The forkhead transcription factor Foxo1 is regulated by insulin via Akt-dependent phosphorylation and nuclear exclusion. |
| 336 | 12530968 | We show that Foxo1 is induced in the early stages of adipocyte differentiation but that its activation is delayed until the end of the clonal expansion phase. |
| 337 | 12530968 | Constitutively active Foxo1 prevents the differentiation of preadipocytes, while dominant-negative Foxo1 restores adipocyte differentiation of fibroblasts from insulin receptor-deficient mice. |
| 338 | 12530968 | We propose that Foxo1 plays an important role in the integration of hormone-activated signaling pathways with the complex transcriptional cascade that promotes adipocyte differentiation. |
| 339 | 12530968 | The forkhead transcription factor Foxo1 regulates adipocyte differentiation. |
| 340 | 12530968 | The forkhead transcription factor Foxo1 is regulated by insulin via Akt-dependent phosphorylation and nuclear exclusion. |
| 341 | 12530968 | We show that Foxo1 is induced in the early stages of adipocyte differentiation but that its activation is delayed until the end of the clonal expansion phase. |
| 342 | 12530968 | Constitutively active Foxo1 prevents the differentiation of preadipocytes, while dominant-negative Foxo1 restores adipocyte differentiation of fibroblasts from insulin receptor-deficient mice. |
| 343 | 12530968 | We propose that Foxo1 plays an important role in the integration of hormone-activated signaling pathways with the complex transcriptional cascade that promotes adipocyte differentiation. |
| 344 | 12530968 | The forkhead transcription factor Foxo1 regulates adipocyte differentiation. |
| 345 | 12530968 | The forkhead transcription factor Foxo1 is regulated by insulin via Akt-dependent phosphorylation and nuclear exclusion. |
| 346 | 12530968 | We show that Foxo1 is induced in the early stages of adipocyte differentiation but that its activation is delayed until the end of the clonal expansion phase. |
| 347 | 12530968 | Constitutively active Foxo1 prevents the differentiation of preadipocytes, while dominant-negative Foxo1 restores adipocyte differentiation of fibroblasts from insulin receptor-deficient mice. |
| 348 | 12530968 | We propose that Foxo1 plays an important role in the integration of hormone-activated signaling pathways with the complex transcriptional cascade that promotes adipocyte differentiation. |
| 349 | 12586369 | A forkhead transcription factor FKHR up-regulates lipoprotein lipase expression in skeletal muscle. |
| 350 | 12586369 | Ectopic expression of FKHR enhanced LPL gene expression in C2C12 muscle cells in culture. |
| 351 | 12586369 | A forkhead transcription factor FKHR up-regulates lipoprotein lipase expression in skeletal muscle. |
| 352 | 12586369 | Ectopic expression of FKHR enhanced LPL gene expression in C2C12 muscle cells in culture. |
| 353 | 12606503 | Regulation of PGC-1 promoter activity by protein kinase B and the forkhead transcription factor FKHR. |
| 354 | 12606503 | Peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) plays a major role in mediating hepatic gluconeogenesis in response to starvation, during which PGC-1 is induced by the cyclic AMP response element binding protein. |
| 355 | 12606503 | Although it is observed that insulin counteracts PGC-1 transcription, the mechanism by which insulin suppresses the transcription of PGC-1 is still unclear. |
| 356 | 12606503 | Here, we show that forkhead transcription factor FKHR contributes to mediating the effects of insulin on PGC-1 promoter activity. |
| 357 | 12606503 | Reporter assays demonstrate that insulin suppresses the basal PGC-1 promoter activity and that coexpression of protein kinase (PK)-B mimics the effect of insulin in HepG2 cells. |
| 358 | 12606503 | Insulin response sequences (IRSs) are addressed in the PGC-1 promoter as the direct target for FKHR in vivo. |
| 359 | 12606503 | Coexpression of FKHR stimulates the PGC-1 promoter activity via interaction with the IRSs, while coexpression of FKHR (3A), in which the three putative PKB sites in FKHR are mutated, mainly abolishes the suppressive effect of PKB. |
| 360 | 12606503 | These results indicate that signaling via PKB to FKHR can partly account for the effect of insulin to regulate the PGC-1 promoter activity via the IRSs. |
| 361 | 12606503 | Regulation of PGC-1 promoter activity by protein kinase B and the forkhead transcription factor FKHR. |
| 362 | 12606503 | Peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) plays a major role in mediating hepatic gluconeogenesis in response to starvation, during which PGC-1 is induced by the cyclic AMP response element binding protein. |
| 363 | 12606503 | Although it is observed that insulin counteracts PGC-1 transcription, the mechanism by which insulin suppresses the transcription of PGC-1 is still unclear. |
| 364 | 12606503 | Here, we show that forkhead transcription factor FKHR contributes to mediating the effects of insulin on PGC-1 promoter activity. |
| 365 | 12606503 | Reporter assays demonstrate that insulin suppresses the basal PGC-1 promoter activity and that coexpression of protein kinase (PK)-B mimics the effect of insulin in HepG2 cells. |
| 366 | 12606503 | Insulin response sequences (IRSs) are addressed in the PGC-1 promoter as the direct target for FKHR in vivo. |
| 367 | 12606503 | Coexpression of FKHR stimulates the PGC-1 promoter activity via interaction with the IRSs, while coexpression of FKHR (3A), in which the three putative PKB sites in FKHR are mutated, mainly abolishes the suppressive effect of PKB. |
| 368 | 12606503 | These results indicate that signaling via PKB to FKHR can partly account for the effect of insulin to regulate the PGC-1 promoter activity via the IRSs. |
| 369 | 12606503 | Regulation of PGC-1 promoter activity by protein kinase B and the forkhead transcription factor FKHR. |
| 370 | 12606503 | Peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) plays a major role in mediating hepatic gluconeogenesis in response to starvation, during which PGC-1 is induced by the cyclic AMP response element binding protein. |
| 371 | 12606503 | Although it is observed that insulin counteracts PGC-1 transcription, the mechanism by which insulin suppresses the transcription of PGC-1 is still unclear. |
| 372 | 12606503 | Here, we show that forkhead transcription factor FKHR contributes to mediating the effects of insulin on PGC-1 promoter activity. |
| 373 | 12606503 | Reporter assays demonstrate that insulin suppresses the basal PGC-1 promoter activity and that coexpression of protein kinase (PK)-B mimics the effect of insulin in HepG2 cells. |
| 374 | 12606503 | Insulin response sequences (IRSs) are addressed in the PGC-1 promoter as the direct target for FKHR in vivo. |
| 375 | 12606503 | Coexpression of FKHR stimulates the PGC-1 promoter activity via interaction with the IRSs, while coexpression of FKHR (3A), in which the three putative PKB sites in FKHR are mutated, mainly abolishes the suppressive effect of PKB. |
| 376 | 12606503 | These results indicate that signaling via PKB to FKHR can partly account for the effect of insulin to regulate the PGC-1 promoter activity via the IRSs. |
| 377 | 12606503 | Regulation of PGC-1 promoter activity by protein kinase B and the forkhead transcription factor FKHR. |
| 378 | 12606503 | Peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) plays a major role in mediating hepatic gluconeogenesis in response to starvation, during which PGC-1 is induced by the cyclic AMP response element binding protein. |
| 379 | 12606503 | Although it is observed that insulin counteracts PGC-1 transcription, the mechanism by which insulin suppresses the transcription of PGC-1 is still unclear. |
| 380 | 12606503 | Here, we show that forkhead transcription factor FKHR contributes to mediating the effects of insulin on PGC-1 promoter activity. |
| 381 | 12606503 | Reporter assays demonstrate that insulin suppresses the basal PGC-1 promoter activity and that coexpression of protein kinase (PK)-B mimics the effect of insulin in HepG2 cells. |
| 382 | 12606503 | Insulin response sequences (IRSs) are addressed in the PGC-1 promoter as the direct target for FKHR in vivo. |
| 383 | 12606503 | Coexpression of FKHR stimulates the PGC-1 promoter activity via interaction with the IRSs, while coexpression of FKHR (3A), in which the three putative PKB sites in FKHR are mutated, mainly abolishes the suppressive effect of PKB. |
| 384 | 12606503 | These results indicate that signaling via PKB to FKHR can partly account for the effect of insulin to regulate the PGC-1 promoter activity via the IRSs. |
| 385 | 12606503 | Regulation of PGC-1 promoter activity by protein kinase B and the forkhead transcription factor FKHR. |
| 386 | 12606503 | Peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) plays a major role in mediating hepatic gluconeogenesis in response to starvation, during which PGC-1 is induced by the cyclic AMP response element binding protein. |
| 387 | 12606503 | Although it is observed that insulin counteracts PGC-1 transcription, the mechanism by which insulin suppresses the transcription of PGC-1 is still unclear. |
| 388 | 12606503 | Here, we show that forkhead transcription factor FKHR contributes to mediating the effects of insulin on PGC-1 promoter activity. |
| 389 | 12606503 | Reporter assays demonstrate that insulin suppresses the basal PGC-1 promoter activity and that coexpression of protein kinase (PK)-B mimics the effect of insulin in HepG2 cells. |
| 390 | 12606503 | Insulin response sequences (IRSs) are addressed in the PGC-1 promoter as the direct target for FKHR in vivo. |
| 391 | 12606503 | Coexpression of FKHR stimulates the PGC-1 promoter activity via interaction with the IRSs, while coexpression of FKHR (3A), in which the three putative PKB sites in FKHR are mutated, mainly abolishes the suppressive effect of PKB. |
| 392 | 12606503 | These results indicate that signaling via PKB to FKHR can partly account for the effect of insulin to regulate the PGC-1 promoter activity via the IRSs. |
| 393 | 12683947 | Three members of this family have been identified in rodents: FoxO1, FoxO3 and FoxO4, originally termed FKHR, FKHRL1 and AFX respectively. |
| 394 | 12683947 | Imposed fasting for 48 h significantly elevated mRNA levels of FoxO1 (1.5-fold), FoxO3 (1.4-fold), and FoxO4 (1.6-fold). |
| 395 | 12683947 | Refeeding for 3 h recovered the induced mRNA levels of FoxO1 and FoxO3 to the control levels, but did not affect that of FoxO4. |
| 396 | 12683947 | FoxO1 and FoxO4 mRNA levels were proved to be highly reflective of their protein levels measured by Western immunoblotting. |
| 397 | 12683947 | Streptozotocin-induced diabetes for 28 days decreased hepatic mRNA levels of FoxO1 and FoxO3 and increased the level of FoxO4 mRNA, but short-term (7 days) diabetes had fewer effects on the expression of these genes. |
| 398 | 12683947 | Insulin replacement partially restored the FoxO1 and FoxO4 mRNA levels, but had no effect on the FoxO3 mRNA level. |
| 399 | 12683947 | Daily administration for 1 week of dexamethasone, a synthetic glucocorticoid, increased the mRNA levels of FoxO1 (1.8-fold) and FoxO3 (2.4-fold). |
| 400 | 12683947 | Moreover, changes of FoxO1 and FoxO4 in the nucleus in response to fasting also suggest that the regulation of nucleus/cytoplasm translocation actually functions in vivo. |
| 401 | 12683947 | Three members of this family have been identified in rodents: FoxO1, FoxO3 and FoxO4, originally termed FKHR, FKHRL1 and AFX respectively. |
| 402 | 12683947 | Imposed fasting for 48 h significantly elevated mRNA levels of FoxO1 (1.5-fold), FoxO3 (1.4-fold), and FoxO4 (1.6-fold). |
| 403 | 12683947 | Refeeding for 3 h recovered the induced mRNA levels of FoxO1 and FoxO3 to the control levels, but did not affect that of FoxO4. |
| 404 | 12683947 | FoxO1 and FoxO4 mRNA levels were proved to be highly reflective of their protein levels measured by Western immunoblotting. |
| 405 | 12683947 | Streptozotocin-induced diabetes for 28 days decreased hepatic mRNA levels of FoxO1 and FoxO3 and increased the level of FoxO4 mRNA, but short-term (7 days) diabetes had fewer effects on the expression of these genes. |
| 406 | 12683947 | Insulin replacement partially restored the FoxO1 and FoxO4 mRNA levels, but had no effect on the FoxO3 mRNA level. |
| 407 | 12683947 | Daily administration for 1 week of dexamethasone, a synthetic glucocorticoid, increased the mRNA levels of FoxO1 (1.8-fold) and FoxO3 (2.4-fold). |
| 408 | 12683947 | Moreover, changes of FoxO1 and FoxO4 in the nucleus in response to fasting also suggest that the regulation of nucleus/cytoplasm translocation actually functions in vivo. |
| 409 | 12683947 | Three members of this family have been identified in rodents: FoxO1, FoxO3 and FoxO4, originally termed FKHR, FKHRL1 and AFX respectively. |
| 410 | 12683947 | Imposed fasting for 48 h significantly elevated mRNA levels of FoxO1 (1.5-fold), FoxO3 (1.4-fold), and FoxO4 (1.6-fold). |
| 411 | 12683947 | Refeeding for 3 h recovered the induced mRNA levels of FoxO1 and FoxO3 to the control levels, but did not affect that of FoxO4. |
| 412 | 12683947 | FoxO1 and FoxO4 mRNA levels were proved to be highly reflective of their protein levels measured by Western immunoblotting. |
| 413 | 12683947 | Streptozotocin-induced diabetes for 28 days decreased hepatic mRNA levels of FoxO1 and FoxO3 and increased the level of FoxO4 mRNA, but short-term (7 days) diabetes had fewer effects on the expression of these genes. |
| 414 | 12683947 | Insulin replacement partially restored the FoxO1 and FoxO4 mRNA levels, but had no effect on the FoxO3 mRNA level. |
| 415 | 12683947 | Daily administration for 1 week of dexamethasone, a synthetic glucocorticoid, increased the mRNA levels of FoxO1 (1.8-fold) and FoxO3 (2.4-fold). |
| 416 | 12683947 | Moreover, changes of FoxO1 and FoxO4 in the nucleus in response to fasting also suggest that the regulation of nucleus/cytoplasm translocation actually functions in vivo. |
| 417 | 12683947 | Three members of this family have been identified in rodents: FoxO1, FoxO3 and FoxO4, originally termed FKHR, FKHRL1 and AFX respectively. |
| 418 | 12683947 | Imposed fasting for 48 h significantly elevated mRNA levels of FoxO1 (1.5-fold), FoxO3 (1.4-fold), and FoxO4 (1.6-fold). |
| 419 | 12683947 | Refeeding for 3 h recovered the induced mRNA levels of FoxO1 and FoxO3 to the control levels, but did not affect that of FoxO4. |
| 420 | 12683947 | FoxO1 and FoxO4 mRNA levels were proved to be highly reflective of their protein levels measured by Western immunoblotting. |
| 421 | 12683947 | Streptozotocin-induced diabetes for 28 days decreased hepatic mRNA levels of FoxO1 and FoxO3 and increased the level of FoxO4 mRNA, but short-term (7 days) diabetes had fewer effects on the expression of these genes. |
| 422 | 12683947 | Insulin replacement partially restored the FoxO1 and FoxO4 mRNA levels, but had no effect on the FoxO3 mRNA level. |
| 423 | 12683947 | Daily administration for 1 week of dexamethasone, a synthetic glucocorticoid, increased the mRNA levels of FoxO1 (1.8-fold) and FoxO3 (2.4-fold). |
| 424 | 12683947 | Moreover, changes of FoxO1 and FoxO4 in the nucleus in response to fasting also suggest that the regulation of nucleus/cytoplasm translocation actually functions in vivo. |
| 425 | 12683947 | Three members of this family have been identified in rodents: FoxO1, FoxO3 and FoxO4, originally termed FKHR, FKHRL1 and AFX respectively. |
| 426 | 12683947 | Imposed fasting for 48 h significantly elevated mRNA levels of FoxO1 (1.5-fold), FoxO3 (1.4-fold), and FoxO4 (1.6-fold). |
| 427 | 12683947 | Refeeding for 3 h recovered the induced mRNA levels of FoxO1 and FoxO3 to the control levels, but did not affect that of FoxO4. |
| 428 | 12683947 | FoxO1 and FoxO4 mRNA levels were proved to be highly reflective of their protein levels measured by Western immunoblotting. |
| 429 | 12683947 | Streptozotocin-induced diabetes for 28 days decreased hepatic mRNA levels of FoxO1 and FoxO3 and increased the level of FoxO4 mRNA, but short-term (7 days) diabetes had fewer effects on the expression of these genes. |
| 430 | 12683947 | Insulin replacement partially restored the FoxO1 and FoxO4 mRNA levels, but had no effect on the FoxO3 mRNA level. |
| 431 | 12683947 | Daily administration for 1 week of dexamethasone, a synthetic glucocorticoid, increased the mRNA levels of FoxO1 (1.8-fold) and FoxO3 (2.4-fold). |
| 432 | 12683947 | Moreover, changes of FoxO1 and FoxO4 in the nucleus in response to fasting also suggest that the regulation of nucleus/cytoplasm translocation actually functions in vivo. |
| 433 | 12683947 | Three members of this family have been identified in rodents: FoxO1, FoxO3 and FoxO4, originally termed FKHR, FKHRL1 and AFX respectively. |
| 434 | 12683947 | Imposed fasting for 48 h significantly elevated mRNA levels of FoxO1 (1.5-fold), FoxO3 (1.4-fold), and FoxO4 (1.6-fold). |
| 435 | 12683947 | Refeeding for 3 h recovered the induced mRNA levels of FoxO1 and FoxO3 to the control levels, but did not affect that of FoxO4. |
| 436 | 12683947 | FoxO1 and FoxO4 mRNA levels were proved to be highly reflective of their protein levels measured by Western immunoblotting. |
| 437 | 12683947 | Streptozotocin-induced diabetes for 28 days decreased hepatic mRNA levels of FoxO1 and FoxO3 and increased the level of FoxO4 mRNA, but short-term (7 days) diabetes had fewer effects on the expression of these genes. |
| 438 | 12683947 | Insulin replacement partially restored the FoxO1 and FoxO4 mRNA levels, but had no effect on the FoxO3 mRNA level. |
| 439 | 12683947 | Daily administration for 1 week of dexamethasone, a synthetic glucocorticoid, increased the mRNA levels of FoxO1 (1.8-fold) and FoxO3 (2.4-fold). |
| 440 | 12683947 | Moreover, changes of FoxO1 and FoxO4 in the nucleus in response to fasting also suggest that the regulation of nucleus/cytoplasm translocation actually functions in vivo. |
| 441 | 12683947 | Three members of this family have been identified in rodents: FoxO1, FoxO3 and FoxO4, originally termed FKHR, FKHRL1 and AFX respectively. |
| 442 | 12683947 | Imposed fasting for 48 h significantly elevated mRNA levels of FoxO1 (1.5-fold), FoxO3 (1.4-fold), and FoxO4 (1.6-fold). |
| 443 | 12683947 | Refeeding for 3 h recovered the induced mRNA levels of FoxO1 and FoxO3 to the control levels, but did not affect that of FoxO4. |
| 444 | 12683947 | FoxO1 and FoxO4 mRNA levels were proved to be highly reflective of their protein levels measured by Western immunoblotting. |
| 445 | 12683947 | Streptozotocin-induced diabetes for 28 days decreased hepatic mRNA levels of FoxO1 and FoxO3 and increased the level of FoxO4 mRNA, but short-term (7 days) diabetes had fewer effects on the expression of these genes. |
| 446 | 12683947 | Insulin replacement partially restored the FoxO1 and FoxO4 mRNA levels, but had no effect on the FoxO3 mRNA level. |
| 447 | 12683947 | Daily administration for 1 week of dexamethasone, a synthetic glucocorticoid, increased the mRNA levels of FoxO1 (1.8-fold) and FoxO3 (2.4-fold). |
| 448 | 12683947 | Moreover, changes of FoxO1 and FoxO4 in the nucleus in response to fasting also suggest that the regulation of nucleus/cytoplasm translocation actually functions in vivo. |
| 449 | 12683947 | Three members of this family have been identified in rodents: FoxO1, FoxO3 and FoxO4, originally termed FKHR, FKHRL1 and AFX respectively. |
| 450 | 12683947 | Imposed fasting for 48 h significantly elevated mRNA levels of FoxO1 (1.5-fold), FoxO3 (1.4-fold), and FoxO4 (1.6-fold). |
| 451 | 12683947 | Refeeding for 3 h recovered the induced mRNA levels of FoxO1 and FoxO3 to the control levels, but did not affect that of FoxO4. |
| 452 | 12683947 | FoxO1 and FoxO4 mRNA levels were proved to be highly reflective of their protein levels measured by Western immunoblotting. |
| 453 | 12683947 | Streptozotocin-induced diabetes for 28 days decreased hepatic mRNA levels of FoxO1 and FoxO3 and increased the level of FoxO4 mRNA, but short-term (7 days) diabetes had fewer effects on the expression of these genes. |
| 454 | 12683947 | Insulin replacement partially restored the FoxO1 and FoxO4 mRNA levels, but had no effect on the FoxO3 mRNA level. |
| 455 | 12683947 | Daily administration for 1 week of dexamethasone, a synthetic glucocorticoid, increased the mRNA levels of FoxO1 (1.8-fold) and FoxO3 (2.4-fold). |
| 456 | 12683947 | Moreover, changes of FoxO1 and FoxO4 in the nucleus in response to fasting also suggest that the regulation of nucleus/cytoplasm translocation actually functions in vivo. |
| 457 | 12724332 | Characterization of insulin inhibition of transactivation by a C-terminal fragment of the forkhead transcription factor Foxo1 in rat hepatoma cells. |
| 458 | 12724332 | In keeping with its important physiological roles, Foxo1 activity is negatively regulated in response to growth factors and cytokines that activate a phosphatidylinositol 3-kinase (PI 3-kinase) protein kinase B (PKB)/Akt pathway. |
| 459 | 12724332 | PKB/Akt-mediated phosphorylation of Foxo1 has been shown to result in the inhibition of target gene transcription and to trigger the export of Foxo1 from the nucleus, which is generally believed to explain the subsequent decrease of transcription. |
| 460 | 12724332 | In the present study, using a chimeric protein in which a C-terminal fragment of Foxo1 (amino acids 208-652) containing the transactivation domain is fused to the yeast Gal4 DNA binding domain, we present evidence showing that insulin can directly regulate transactivation by Foxo1 in H4IIE rat hepatoma cells. |
| 461 | 12724332 | 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. |
| 462 | 12724332 | We conclude that the transcriptional activity of Foxo1 is regulated at different levels by insulin: transactivation, as well as DNA binding and nuclear exclusion. |
| 463 | 12724332 | Characterization of insulin inhibition of transactivation by a C-terminal fragment of the forkhead transcription factor Foxo1 in rat hepatoma cells. |
| 464 | 12724332 | In keeping with its important physiological roles, Foxo1 activity is negatively regulated in response to growth factors and cytokines that activate a phosphatidylinositol 3-kinase (PI 3-kinase) protein kinase B (PKB)/Akt pathway. |
| 465 | 12724332 | PKB/Akt-mediated phosphorylation of Foxo1 has been shown to result in the inhibition of target gene transcription and to trigger the export of Foxo1 from the nucleus, which is generally believed to explain the subsequent decrease of transcription. |
| 466 | 12724332 | In the present study, using a chimeric protein in which a C-terminal fragment of Foxo1 (amino acids 208-652) containing the transactivation domain is fused to the yeast Gal4 DNA binding domain, we present evidence showing that insulin can directly regulate transactivation by Foxo1 in H4IIE rat hepatoma cells. |
| 467 | 12724332 | 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. |
| 468 | 12724332 | We conclude that the transcriptional activity of Foxo1 is regulated at different levels by insulin: transactivation, as well as DNA binding and nuclear exclusion. |
| 469 | 12724332 | Characterization of insulin inhibition of transactivation by a C-terminal fragment of the forkhead transcription factor Foxo1 in rat hepatoma cells. |
| 470 | 12724332 | In keeping with its important physiological roles, Foxo1 activity is negatively regulated in response to growth factors and cytokines that activate a phosphatidylinositol 3-kinase (PI 3-kinase) protein kinase B (PKB)/Akt pathway. |
| 471 | 12724332 | PKB/Akt-mediated phosphorylation of Foxo1 has been shown to result in the inhibition of target gene transcription and to trigger the export of Foxo1 from the nucleus, which is generally believed to explain the subsequent decrease of transcription. |
| 472 | 12724332 | In the present study, using a chimeric protein in which a C-terminal fragment of Foxo1 (amino acids 208-652) containing the transactivation domain is fused to the yeast Gal4 DNA binding domain, we present evidence showing that insulin can directly regulate transactivation by Foxo1 in H4IIE rat hepatoma cells. |
| 473 | 12724332 | 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. |
| 474 | 12724332 | We conclude that the transcriptional activity of Foxo1 is regulated at different levels by insulin: transactivation, as well as DNA binding and nuclear exclusion. |
| 475 | 12724332 | Characterization of insulin inhibition of transactivation by a C-terminal fragment of the forkhead transcription factor Foxo1 in rat hepatoma cells. |
| 476 | 12724332 | In keeping with its important physiological roles, Foxo1 activity is negatively regulated in response to growth factors and cytokines that activate a phosphatidylinositol 3-kinase (PI 3-kinase) protein kinase B (PKB)/Akt pathway. |
| 477 | 12724332 | PKB/Akt-mediated phosphorylation of Foxo1 has been shown to result in the inhibition of target gene transcription and to trigger the export of Foxo1 from the nucleus, which is generally believed to explain the subsequent decrease of transcription. |
| 478 | 12724332 | In the present study, using a chimeric protein in which a C-terminal fragment of Foxo1 (amino acids 208-652) containing the transactivation domain is fused to the yeast Gal4 DNA binding domain, we present evidence showing that insulin can directly regulate transactivation by Foxo1 in H4IIE rat hepatoma cells. |
| 479 | 12724332 | 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. |
| 480 | 12724332 | We conclude that the transcriptional activity of Foxo1 is regulated at different levels by insulin: transactivation, as well as DNA binding and nuclear exclusion. |
| 481 | 12724332 | Characterization of insulin inhibition of transactivation by a C-terminal fragment of the forkhead transcription factor Foxo1 in rat hepatoma cells. |
| 482 | 12724332 | In keeping with its important physiological roles, Foxo1 activity is negatively regulated in response to growth factors and cytokines that activate a phosphatidylinositol 3-kinase (PI 3-kinase) protein kinase B (PKB)/Akt pathway. |
| 483 | 12724332 | PKB/Akt-mediated phosphorylation of Foxo1 has been shown to result in the inhibition of target gene transcription and to trigger the export of Foxo1 from the nucleus, which is generally believed to explain the subsequent decrease of transcription. |
| 484 | 12724332 | In the present study, using a chimeric protein in which a C-terminal fragment of Foxo1 (amino acids 208-652) containing the transactivation domain is fused to the yeast Gal4 DNA binding domain, we present evidence showing that insulin can directly regulate transactivation by Foxo1 in H4IIE rat hepatoma cells. |
| 485 | 12724332 | 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. |
| 486 | 12724332 | We conclude that the transcriptional activity of Foxo1 is regulated at different levels by insulin: transactivation, as well as DNA binding and nuclear exclusion. |
| 487 | 12724332 | Characterization of insulin inhibition of transactivation by a C-terminal fragment of the forkhead transcription factor Foxo1 in rat hepatoma cells. |
| 488 | 12724332 | In keeping with its important physiological roles, Foxo1 activity is negatively regulated in response to growth factors and cytokines that activate a phosphatidylinositol 3-kinase (PI 3-kinase) protein kinase B (PKB)/Akt pathway. |
| 489 | 12724332 | PKB/Akt-mediated phosphorylation of Foxo1 has been shown to result in the inhibition of target gene transcription and to trigger the export of Foxo1 from the nucleus, which is generally believed to explain the subsequent decrease of transcription. |
| 490 | 12724332 | In the present study, using a chimeric protein in which a C-terminal fragment of Foxo1 (amino acids 208-652) containing the transactivation domain is fused to the yeast Gal4 DNA binding domain, we present evidence showing that insulin can directly regulate transactivation by Foxo1 in H4IIE rat hepatoma cells. |
| 491 | 12724332 | 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. |
| 492 | 12724332 | We conclude that the transcriptional activity of Foxo1 is regulated at different levels by insulin: transactivation, as well as DNA binding and nuclear exclusion. |
| 493 | 12754525 | Two components known to have important physiological roles in this process are the forkhead transcription factor FOXO1 (also known as FKHR) and peroxisome proliferative activated receptor-gamma co-activator 1 (PGC-1alpha; also known as PPARGC1), a transcriptional co-activator; whether and how these factors collaborate has not been clear. |
| 494 | 12754525 | Using wild-type and mutant alleles of FOXO1, here we show that PGC-1alpha binds and co-activates FOXO1 in a manner inhibited by Akt-mediated phosphorylation. |
| 495 | 12754525 | Furthermore, FOXO1 function is required for the robust activation of gluconeogenic gene expression in hepatic cells and in mouse liver by PGC-1alpha. |
| 496 | 12754525 | Insulin suppresses gluconeogenesis stimulated by PGC-1alpha but co-expression of a mutant allele of FOXO1 insensitive to insulin completely reverses this suppression in hepatocytes or transgenic mice. |
| 497 | 12754525 | We conclude that FOXO1 and PGC-1alpha interact in the execution of a programme of powerful, insulin-regulated gluconeogenesis. |
| 498 | 12754525 | Two components known to have important physiological roles in this process are the forkhead transcription factor FOXO1 (also known as FKHR) and peroxisome proliferative activated receptor-gamma co-activator 1 (PGC-1alpha; also known as PPARGC1), a transcriptional co-activator; whether and how these factors collaborate has not been clear. |
| 499 | 12754525 | Using wild-type and mutant alleles of FOXO1, here we show that PGC-1alpha binds and co-activates FOXO1 in a manner inhibited by Akt-mediated phosphorylation. |
| 500 | 12754525 | Furthermore, FOXO1 function is required for the robust activation of gluconeogenic gene expression in hepatic cells and in mouse liver by PGC-1alpha. |
| 501 | 12754525 | Insulin suppresses gluconeogenesis stimulated by PGC-1alpha but co-expression of a mutant allele of FOXO1 insensitive to insulin completely reverses this suppression in hepatocytes or transgenic mice. |
| 502 | 12754525 | We conclude that FOXO1 and PGC-1alpha interact in the execution of a programme of powerful, insulin-regulated gluconeogenesis. |
| 503 | 12754525 | Two components known to have important physiological roles in this process are the forkhead transcription factor FOXO1 (also known as FKHR) and peroxisome proliferative activated receptor-gamma co-activator 1 (PGC-1alpha; also known as PPARGC1), a transcriptional co-activator; whether and how these factors collaborate has not been clear. |
| 504 | 12754525 | Using wild-type and mutant alleles of FOXO1, here we show that PGC-1alpha binds and co-activates FOXO1 in a manner inhibited by Akt-mediated phosphorylation. |
| 505 | 12754525 | Furthermore, FOXO1 function is required for the robust activation of gluconeogenic gene expression in hepatic cells and in mouse liver by PGC-1alpha. |
| 506 | 12754525 | Insulin suppresses gluconeogenesis stimulated by PGC-1alpha but co-expression of a mutant allele of FOXO1 insensitive to insulin completely reverses this suppression in hepatocytes or transgenic mice. |
| 507 | 12754525 | We conclude that FOXO1 and PGC-1alpha interact in the execution of a programme of powerful, insulin-regulated gluconeogenesis. |
| 508 | 12754525 | Two components known to have important physiological roles in this process are the forkhead transcription factor FOXO1 (also known as FKHR) and peroxisome proliferative activated receptor-gamma co-activator 1 (PGC-1alpha; also known as PPARGC1), a transcriptional co-activator; whether and how these factors collaborate has not been clear. |
| 509 | 12754525 | Using wild-type and mutant alleles of FOXO1, here we show that PGC-1alpha binds and co-activates FOXO1 in a manner inhibited by Akt-mediated phosphorylation. |
| 510 | 12754525 | Furthermore, FOXO1 function is required for the robust activation of gluconeogenic gene expression in hepatic cells and in mouse liver by PGC-1alpha. |
| 511 | 12754525 | Insulin suppresses gluconeogenesis stimulated by PGC-1alpha but co-expression of a mutant allele of FOXO1 insensitive to insulin completely reverses this suppression in hepatocytes or transgenic mice. |
| 512 | 12754525 | We conclude that FOXO1 and PGC-1alpha interact in the execution of a programme of powerful, insulin-regulated gluconeogenesis. |
| 513 | 12754525 | Two components known to have important physiological roles in this process are the forkhead transcription factor FOXO1 (also known as FKHR) and peroxisome proliferative activated receptor-gamma co-activator 1 (PGC-1alpha; also known as PPARGC1), a transcriptional co-activator; whether and how these factors collaborate has not been clear. |
| 514 | 12754525 | Using wild-type and mutant alleles of FOXO1, here we show that PGC-1alpha binds and co-activates FOXO1 in a manner inhibited by Akt-mediated phosphorylation. |
| 515 | 12754525 | Furthermore, FOXO1 function is required for the robust activation of gluconeogenic gene expression in hepatic cells and in mouse liver by PGC-1alpha. |
| 516 | 12754525 | Insulin suppresses gluconeogenesis stimulated by PGC-1alpha but co-expression of a mutant allele of FOXO1 insensitive to insulin completely reverses this suppression in hepatocytes or transgenic mice. |
| 517 | 12754525 | We conclude that FOXO1 and PGC-1alpha interact in the execution of a programme of powerful, insulin-regulated gluconeogenesis. |
| 518 | 12783775 | Insulin suppresses hepatic glucose production by inhibiting the expression of two gluconeogenic enzymes, phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase). |
| 519 | 12783775 | The forkhead transcription factor Foxo1 has been implicated as a mediator of insulin action in regulating hepatic gluconeogenesis, and a Foxo1 mutant (Foxo1-Delta256), devoid of its carboxyl domain, has been shown to interfere with Foxo1 function and inhibit gluconeogenic gene expression in cultured cells. |
| 520 | 12783775 | Hepatic Foxo1-Delta256 production resulted in inhibition of gluconeogenic activity, as evidenced by reduced PEPCK and G-6-Pase expression in the liver. |
| 521 | 12783775 | Furthermore, we showed that hepatic Foxo1 expression was deregulated as a result of insulin resistance in diabetic mice and that Foxo1-Delta256 interfered with Foxo1 function via competitive binding to target promoters. |
| 522 | 12783775 | Insulin suppresses hepatic glucose production by inhibiting the expression of two gluconeogenic enzymes, phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase). |
| 523 | 12783775 | The forkhead transcription factor Foxo1 has been implicated as a mediator of insulin action in regulating hepatic gluconeogenesis, and a Foxo1 mutant (Foxo1-Delta256), devoid of its carboxyl domain, has been shown to interfere with Foxo1 function and inhibit gluconeogenic gene expression in cultured cells. |
| 524 | 12783775 | Hepatic Foxo1-Delta256 production resulted in inhibition of gluconeogenic activity, as evidenced by reduced PEPCK and G-6-Pase expression in the liver. |
| 525 | 12783775 | Furthermore, we showed that hepatic Foxo1 expression was deregulated as a result of insulin resistance in diabetic mice and that Foxo1-Delta256 interfered with Foxo1 function via competitive binding to target promoters. |
| 526 | 12783775 | Insulin suppresses hepatic glucose production by inhibiting the expression of two gluconeogenic enzymes, phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase). |
| 527 | 12783775 | The forkhead transcription factor Foxo1 has been implicated as a mediator of insulin action in regulating hepatic gluconeogenesis, and a Foxo1 mutant (Foxo1-Delta256), devoid of its carboxyl domain, has been shown to interfere with Foxo1 function and inhibit gluconeogenic gene expression in cultured cells. |
| 528 | 12783775 | Hepatic Foxo1-Delta256 production resulted in inhibition of gluconeogenic activity, as evidenced by reduced PEPCK and G-6-Pase expression in the liver. |
| 529 | 12783775 | Furthermore, we showed that hepatic Foxo1 expression was deregulated as a result of insulin resistance in diabetic mice and that Foxo1-Delta256 interfered with Foxo1 function via competitive binding to target promoters. |
| 530 | 12807885 | Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) is a transcriptional coactivator that regulates multiple aspects of cellular energy metabolism, including mitochondrial biogenesis, hepatic gluconeogenesis, and beta-oxidation of fatty acids. |
| 531 | 12807885 | We have recently described PGC-1beta, a novel transcriptional coactivator that is a homolog of PGC-1alpha. |
| 532 | 12807885 | Although PGC-1beta shares significant sequence similarity and tissue distribution with PGC-1alpha, the biological activities of PGC-1beta in the regulation of cellular metabolism is unknown. |
| 533 | 12807885 | PGC-1beta, like PGC-1alpha, potently induces the expression of an array of mitochondrial genes involved in oxidative metabolism. |
| 534 | 12807885 | However, in contrast to PGC-1alpha, PGC-1beta poorly activates the expression of gluconeogenic genes in hepatocytes or liver in vivo, illustrating that these two coactivators play distinct roles in hepatic glucose metabolism. |
| 535 | 12807885 | The reduced ability of PGC-1beta to induce gluconeogenic genes is due, at least in part, to its inability to physically associate with and coactivate hepatic nuclear receptor 4alpha (HNF4alpha) and forkhead transcription factor O1 (FOXO1), two critical transcription factors that mediate the activation of gluconeogenic gene expression by PGC-1alpha. |
| 536 | 12807885 | These data illustrate that PGC-1beta and PGC-1alpha have distinct arrays of activities in hepatic energy metabolism. |
| 537 | 14500580 | Insulin inhibition of transcription stimulated by the forkhead protein Foxo1 is not solely due to nuclear exclusion. |
| 538 | 14500580 | The activity of FOXO proteins is principally regulated by activation of protein kinase B (PKB)/Akt by insulin and other cytokines. |
| 539 | 14500580 | In the present study we mutated Leu375 to alanine in the nuclear export signal of Foxo1 (mouse FOXO1), so that it would remain in the nucleus of H4IIE rat hepatoma cells after insulin treatment, and determined whether insulin could still inhibit transcription stimulated by the Foxo1 mutant. |
| 540 | 14500580 | Despite the retention of the Foxo1 mutant in the nucleus, insulin inhibited L375A-Foxo1-stimulated transcription to the same extent as transcription stimulated by wild-type Foxo1. |
| 541 | 14500580 | Similar results were obtained using reporter plasmids containing the rat IGF-binding protein-1 promoter or a minimal promoter with three copies of the insulin response element to which FOXO proteins bind. |
| 542 | 14500580 | We conclude that insulin can inhibit Foxo1-stimulated transcription even when nuclear export of Foxo1 is prevented, indicating that insulin inhibition can occur by direct mechanisms that do not depend on altering the subcellular distribution of the transcription factor. |
| 543 | 14500580 | Insulin inhibition of transcription stimulated by the forkhead protein Foxo1 is not solely due to nuclear exclusion. |
| 544 | 14500580 | The activity of FOXO proteins is principally regulated by activation of protein kinase B (PKB)/Akt by insulin and other cytokines. |
| 545 | 14500580 | In the present study we mutated Leu375 to alanine in the nuclear export signal of Foxo1 (mouse FOXO1), so that it would remain in the nucleus of H4IIE rat hepatoma cells after insulin treatment, and determined whether insulin could still inhibit transcription stimulated by the Foxo1 mutant. |
| 546 | 14500580 | Despite the retention of the Foxo1 mutant in the nucleus, insulin inhibited L375A-Foxo1-stimulated transcription to the same extent as transcription stimulated by wild-type Foxo1. |
| 547 | 14500580 | Similar results were obtained using reporter plasmids containing the rat IGF-binding protein-1 promoter or a minimal promoter with three copies of the insulin response element to which FOXO proteins bind. |
| 548 | 14500580 | We conclude that insulin can inhibit Foxo1-stimulated transcription even when nuclear export of Foxo1 is prevented, indicating that insulin inhibition can occur by direct mechanisms that do not depend on altering the subcellular distribution of the transcription factor. |
| 549 | 14500580 | Insulin inhibition of transcription stimulated by the forkhead protein Foxo1 is not solely due to nuclear exclusion. |
| 550 | 14500580 | The activity of FOXO proteins is principally regulated by activation of protein kinase B (PKB)/Akt by insulin and other cytokines. |
| 551 | 14500580 | In the present study we mutated Leu375 to alanine in the nuclear export signal of Foxo1 (mouse FOXO1), so that it would remain in the nucleus of H4IIE rat hepatoma cells after insulin treatment, and determined whether insulin could still inhibit transcription stimulated by the Foxo1 mutant. |
| 552 | 14500580 | Despite the retention of the Foxo1 mutant in the nucleus, insulin inhibited L375A-Foxo1-stimulated transcription to the same extent as transcription stimulated by wild-type Foxo1. |
| 553 | 14500580 | Similar results were obtained using reporter plasmids containing the rat IGF-binding protein-1 promoter or a minimal promoter with three copies of the insulin response element to which FOXO proteins bind. |
| 554 | 14500580 | We conclude that insulin can inhibit Foxo1-stimulated transcription even when nuclear export of Foxo1 is prevented, indicating that insulin inhibition can occur by direct mechanisms that do not depend on altering the subcellular distribution of the transcription factor. |
| 555 | 14500580 | Insulin inhibition of transcription stimulated by the forkhead protein Foxo1 is not solely due to nuclear exclusion. |
| 556 | 14500580 | The activity of FOXO proteins is principally regulated by activation of protein kinase B (PKB)/Akt by insulin and other cytokines. |
| 557 | 14500580 | In the present study we mutated Leu375 to alanine in the nuclear export signal of Foxo1 (mouse FOXO1), so that it would remain in the nucleus of H4IIE rat hepatoma cells after insulin treatment, and determined whether insulin could still inhibit transcription stimulated by the Foxo1 mutant. |
| 558 | 14500580 | Despite the retention of the Foxo1 mutant in the nucleus, insulin inhibited L375A-Foxo1-stimulated transcription to the same extent as transcription stimulated by wild-type Foxo1. |
| 559 | 14500580 | Similar results were obtained using reporter plasmids containing the rat IGF-binding protein-1 promoter or a minimal promoter with three copies of the insulin response element to which FOXO proteins bind. |
| 560 | 14500580 | We conclude that insulin can inhibit Foxo1-stimulated transcription even when nuclear export of Foxo1 is prevented, indicating that insulin inhibition can occur by direct mechanisms that do not depend on altering the subcellular distribution of the transcription factor. |
| 561 | 15047604 | Protein kinase B-alpha inhibits human pyruvate dehydrogenase kinase-4 gene induction by dexamethasone through inactivation of FOXO transcription factors. |
| 562 | 15047604 | Starvation and diabetes increase pyruvate dehydrogenase kinase-4 (PDK4) expression, which conserves gluconeogenic substrates by inactivating the pyruvate dehydrogenase complex. |
| 563 | 15047604 | Mechanisms that regulate PDK4 gene expression, previously established to be increased by glucocorticoids and decreased by insulin, were studied. |
| 564 | 15047604 | Treatment of HepG2 cells with dexamethasone increases the relative abundance of PDK4 mRNA, and insulin blocks this effect. |
| 565 | 15047604 | Dexamethasone also increases human PDK4 (hPDK4) promoter activity in HepG2 cells, and insulin partially inhibits this effect. |
| 566 | 15047604 | Expression of constitutively active PKB alpha abrogates dexamethasone stimulation of hPDK4 promoter activity, while coexpression of constitutively active FOXO1a or FOXO3a, which are mutated to alanine at the three phosphorylation sites for protein kinase B (PKB), disrupts the ability of PKB alpha to inhibit promoter activity. |
| 567 | 15047604 | A glucocorticoid response element for glucocorticoid receptor (GR) binding and three insulin response sequences (IRSs) that bind FOXO1a and FOXO3a are identified in the hPDK4 promoter. |
| 568 | 15047604 | Transfection studies with E1A, which binds to and inactivates p300/CBP, suggest that interactions between p300/CBP and GR as well as FOXO factors are important for glucocorticoid-stimulated hPDK4 expression. |
| 569 | 15047604 | Insulin suppresses the hPDK4 induction by glucocorticoids through inactivation of the FOXO factors. |
| 570 | 15047604 | Protein kinase B-alpha inhibits human pyruvate dehydrogenase kinase-4 gene induction by dexamethasone through inactivation of FOXO transcription factors. |
| 571 | 15047604 | Starvation and diabetes increase pyruvate dehydrogenase kinase-4 (PDK4) expression, which conserves gluconeogenic substrates by inactivating the pyruvate dehydrogenase complex. |
| 572 | 15047604 | Mechanisms that regulate PDK4 gene expression, previously established to be increased by glucocorticoids and decreased by insulin, were studied. |
| 573 | 15047604 | Treatment of HepG2 cells with dexamethasone increases the relative abundance of PDK4 mRNA, and insulin blocks this effect. |
| 574 | 15047604 | Dexamethasone also increases human PDK4 (hPDK4) promoter activity in HepG2 cells, and insulin partially inhibits this effect. |
| 575 | 15047604 | Expression of constitutively active PKB alpha abrogates dexamethasone stimulation of hPDK4 promoter activity, while coexpression of constitutively active FOXO1a or FOXO3a, which are mutated to alanine at the three phosphorylation sites for protein kinase B (PKB), disrupts the ability of PKB alpha to inhibit promoter activity. |
| 576 | 15047604 | A glucocorticoid response element for glucocorticoid receptor (GR) binding and three insulin response sequences (IRSs) that bind FOXO1a and FOXO3a are identified in the hPDK4 promoter. |
| 577 | 15047604 | Transfection studies with E1A, which binds to and inactivates p300/CBP, suggest that interactions between p300/CBP and GR as well as FOXO factors are important for glucocorticoid-stimulated hPDK4 expression. |
| 578 | 15047604 | Insulin suppresses the hPDK4 induction by glucocorticoids through inactivation of the FOXO factors. |
| 579 | 15272020 | Enhanced gene expression of a lysosomal proteinase, cathepsin L, which is known to be up-regulated during skeletal muscle atrophy, suggested increased protein degradation in the skeletal muscle of FOXO1 mice. |
| 580 | 15272020 | Moreover, the FOXO1 mice showed impaired glycemic control after oral glucose and intraperitoneal insulin administration. |
| 581 | 15272020 | Enhanced gene expression of a lysosomal proteinase, cathepsin L, which is known to be up-regulated during skeletal muscle atrophy, suggested increased protein degradation in the skeletal muscle of FOXO1 mice. |
| 582 | 15272020 | Moreover, the FOXO1 mice showed impaired glycemic control after oral glucose and intraperitoneal insulin administration. |
| 583 | 15492844 | Human Forkhead-box (FOX) gene family consists of at least 43 members, including FOXA1, FOXA2, FOXA3, FOXB1, FOXC1, FOXC2, FOXD1, FOXD2, FOXD3, FOXD4, FOXD5 (FOXD4L1), FOXD6 (FOXD4L3), FOXE1, FOXE2, FOXE3, FOXF1, FOXF2, FOXG1 (FOXG1B), FOXH1, FOXI1, FOXJ1, FOXJ2, FOXJ3, FOXK1, FOXK2, FOXL1, FOXL2, FOXM1, FOXN1, FOXN2 (HTLF), FOXN3 (CHES1), FOXN4, FOXN5 (FOXR1), FOXN6 (FOXR2), FOXO1 (FOXO1A), FOXO2 (FOXO6), FOXO3 (FOXO3A), FOXO4 (MLLT7), FOXP1, FOXP2, FOXP3, FOXP4, and FOXQ1. |
| 584 | 15492844 | FOXH1 and FOXO1 mRNAs are expressed in human embryonic stem (ES) cells. |
| 585 | 15492844 | FOXC1, FOXC2, FOXE1, FOXE3, FOXL2, FOXN1, FOXP2 and FOXP3 genes are mutated in human congenital disorders. |
| 586 | 15492844 | FOXM1 gene is up-regulated in pancreatic cancer and basal cell carcinoma due to the transcriptional regulation by Sonic Hedgehog (SHH) pathway. |
| 587 | 15492844 | FOXO1 gene is fused to PAX3 or PAX7 genes in rhabdomyosarcoma. |
| 588 | 15492844 | FOXO3 and FOXO4 genes are fused to MLL gene in hematological malignancies. |
| 589 | 15492844 | Human Forkhead-box (FOX) gene family consists of at least 43 members, including FOXA1, FOXA2, FOXA3, FOXB1, FOXC1, FOXC2, FOXD1, FOXD2, FOXD3, FOXD4, FOXD5 (FOXD4L1), FOXD6 (FOXD4L3), FOXE1, FOXE2, FOXE3, FOXF1, FOXF2, FOXG1 (FOXG1B), FOXH1, FOXI1, FOXJ1, FOXJ2, FOXJ3, FOXK1, FOXK2, FOXL1, FOXL2, FOXM1, FOXN1, FOXN2 (HTLF), FOXN3 (CHES1), FOXN4, FOXN5 (FOXR1), FOXN6 (FOXR2), FOXO1 (FOXO1A), FOXO2 (FOXO6), FOXO3 (FOXO3A), FOXO4 (MLLT7), FOXP1, FOXP2, FOXP3, FOXP4, and FOXQ1. |
| 590 | 15492844 | FOXH1 and FOXO1 mRNAs are expressed in human embryonic stem (ES) cells. |
| 591 | 15492844 | FOXC1, FOXC2, FOXE1, FOXE3, FOXL2, FOXN1, FOXP2 and FOXP3 genes are mutated in human congenital disorders. |
| 592 | 15492844 | FOXM1 gene is up-regulated in pancreatic cancer and basal cell carcinoma due to the transcriptional regulation by Sonic Hedgehog (SHH) pathway. |
| 593 | 15492844 | FOXO1 gene is fused to PAX3 or PAX7 genes in rhabdomyosarcoma. |
| 594 | 15492844 | FOXO3 and FOXO4 genes are fused to MLL gene in hematological malignancies. |
| 595 | 15492844 | Human Forkhead-box (FOX) gene family consists of at least 43 members, including FOXA1, FOXA2, FOXA3, FOXB1, FOXC1, FOXC2, FOXD1, FOXD2, FOXD3, FOXD4, FOXD5 (FOXD4L1), FOXD6 (FOXD4L3), FOXE1, FOXE2, FOXE3, FOXF1, FOXF2, FOXG1 (FOXG1B), FOXH1, FOXI1, FOXJ1, FOXJ2, FOXJ3, FOXK1, FOXK2, FOXL1, FOXL2, FOXM1, FOXN1, FOXN2 (HTLF), FOXN3 (CHES1), FOXN4, FOXN5 (FOXR1), FOXN6 (FOXR2), FOXO1 (FOXO1A), FOXO2 (FOXO6), FOXO3 (FOXO3A), FOXO4 (MLLT7), FOXP1, FOXP2, FOXP3, FOXP4, and FOXQ1. |
| 596 | 15492844 | FOXH1 and FOXO1 mRNAs are expressed in human embryonic stem (ES) cells. |
| 597 | 15492844 | FOXC1, FOXC2, FOXE1, FOXE3, FOXL2, FOXN1, FOXP2 and FOXP3 genes are mutated in human congenital disorders. |
| 598 | 15492844 | FOXM1 gene is up-regulated in pancreatic cancer and basal cell carcinoma due to the transcriptional regulation by Sonic Hedgehog (SHH) pathway. |
| 599 | 15492844 | FOXO1 gene is fused to PAX3 or PAX7 genes in rhabdomyosarcoma. |
| 600 | 15492844 | FOXO3 and FOXO4 genes are fused to MLL gene in hematological malignancies. |
| 601 | 15631623 | The three Fox (forkhead box) group A genes, Foxa1, Foxa2 and Foxa3, are expressed in embryonic endoderm, the germ layer that gives rise to the digestive system, and contribute to the specification of the pancreas and the regulation of glucose homoeostasis. |
| 602 | 15631623 | Deletion of the Foxa2 gene in pancreatic beta-cells in mice results in a phenotype resembling PHHI (persistent hyperinsulinaemic hypoglycaemia of infancy). |
| 603 | 15631623 | Molecular analyses have demonstrated that Foxa2 is an important regulator of the genes encoding Sur1, Kir6.2 and Schad (short chain L-3-hydroxyacyl-CoA dehydrogenase), mutation of which causes PHHI in humans. |
| 604 | 15631623 | An additional winged-helix protein, Foxo1, contributes to pancreatic beta-cell function by regulating the Pdx1 gene, which is required for pancreatic development in cooperation with Foxa2. |
| 605 | 15652518 | To address the mechanism of beta cell regeneration, mice were treated with streptozotocin (STZ group) or streptozotocin and exendin-4 (STZ + Ex-4 group), and the expression of PDX-1, Ngn3, insulin, IRS-2, and Foxo1 was investigated. |
| 606 | 15652518 | Exendin-4 upregulated PDX-1 expression which paralleled increased IRS-2 expression and translocation of Foxo1 from nucleus to cytoplasm. |
| 607 | 15671479 | Foxo1, a member of the Fox0 subfamily of winged-helix forkhead transcription factors, is a target of insulin and insulin-like growth factor-1 (IGF-1) signal transduction pathways that activate protein kinase B (PKB) in pancreatic beta cells. |
| 608 | 15671479 | Foxo1 is a substrate for PKB, and its phosphorylation results in nuclear exclusion with concomitant alterations in gene expression that are important to cellular growth and differentiation. |
| 609 | 15671479 | Because activation of PKB can require insulin receptor substrate proteins (IRS-1 and IRS-2) and phosphatidylinositol 3-kinase (PI3K), it is of interest to determine whether the activity of Foxo1 is also regulated by heterotrimeric G protein-coupled receptors (GPCRs) with IRS-1 or -2, PI3K, or PKB signaling potential. |
| 610 | 15671479 | Indeed, studies of beta cells have demonstrated that activation of a GPCR for the blood glucose-lowering hormone GLP-1 leads to major alterations of IRS-2, PI3K, and PKB activity. |
| 611 | 15671479 | By promoting nuclear exclusion of Foxo1 in a PKB-mediated manner, GLP-1 may up-regulate the expression of a homeodomain transcription factor (PDX-1) that serves as a master regulator of beta-cell growth and differentiation. |
| 612 | 15671479 | Foxo1, a member of the Fox0 subfamily of winged-helix forkhead transcription factors, is a target of insulin and insulin-like growth factor-1 (IGF-1) signal transduction pathways that activate protein kinase B (PKB) in pancreatic beta cells. |
| 613 | 15671479 | Foxo1 is a substrate for PKB, and its phosphorylation results in nuclear exclusion with concomitant alterations in gene expression that are important to cellular growth and differentiation. |
| 614 | 15671479 | Because activation of PKB can require insulin receptor substrate proteins (IRS-1 and IRS-2) and phosphatidylinositol 3-kinase (PI3K), it is of interest to determine whether the activity of Foxo1 is also regulated by heterotrimeric G protein-coupled receptors (GPCRs) with IRS-1 or -2, PI3K, or PKB signaling potential. |
| 615 | 15671479 | Indeed, studies of beta cells have demonstrated that activation of a GPCR for the blood glucose-lowering hormone GLP-1 leads to major alterations of IRS-2, PI3K, and PKB activity. |
| 616 | 15671479 | By promoting nuclear exclusion of Foxo1 in a PKB-mediated manner, GLP-1 may up-regulate the expression of a homeodomain transcription factor (PDX-1) that serves as a master regulator of beta-cell growth and differentiation. |
| 617 | 15671479 | Foxo1, a member of the Fox0 subfamily of winged-helix forkhead transcription factors, is a target of insulin and insulin-like growth factor-1 (IGF-1) signal transduction pathways that activate protein kinase B (PKB) in pancreatic beta cells. |
| 618 | 15671479 | Foxo1 is a substrate for PKB, and its phosphorylation results in nuclear exclusion with concomitant alterations in gene expression that are important to cellular growth and differentiation. |
| 619 | 15671479 | Because activation of PKB can require insulin receptor substrate proteins (IRS-1 and IRS-2) and phosphatidylinositol 3-kinase (PI3K), it is of interest to determine whether the activity of Foxo1 is also regulated by heterotrimeric G protein-coupled receptors (GPCRs) with IRS-1 or -2, PI3K, or PKB signaling potential. |
| 620 | 15671479 | Indeed, studies of beta cells have demonstrated that activation of a GPCR for the blood glucose-lowering hormone GLP-1 leads to major alterations of IRS-2, PI3K, and PKB activity. |
| 621 | 15671479 | By promoting nuclear exclusion of Foxo1 in a PKB-mediated manner, GLP-1 may up-regulate the expression of a homeodomain transcription factor (PDX-1) that serves as a master regulator of beta-cell growth and differentiation. |
| 622 | 15671479 | Foxo1, a member of the Fox0 subfamily of winged-helix forkhead transcription factors, is a target of insulin and insulin-like growth factor-1 (IGF-1) signal transduction pathways that activate protein kinase B (PKB) in pancreatic beta cells. |
| 623 | 15671479 | Foxo1 is a substrate for PKB, and its phosphorylation results in nuclear exclusion with concomitant alterations in gene expression that are important to cellular growth and differentiation. |
| 624 | 15671479 | Because activation of PKB can require insulin receptor substrate proteins (IRS-1 and IRS-2) and phosphatidylinositol 3-kinase (PI3K), it is of interest to determine whether the activity of Foxo1 is also regulated by heterotrimeric G protein-coupled receptors (GPCRs) with IRS-1 or -2, PI3K, or PKB signaling potential. |
| 625 | 15671479 | Indeed, studies of beta cells have demonstrated that activation of a GPCR for the blood glucose-lowering hormone GLP-1 leads to major alterations of IRS-2, PI3K, and PKB activity. |
| 626 | 15671479 | By promoting nuclear exclusion of Foxo1 in a PKB-mediated manner, GLP-1 may up-regulate the expression of a homeodomain transcription factor (PDX-1) that serves as a master regulator of beta-cell growth and differentiation. |
| 627 | 15677515 | The phosphorylation of two downstream targets of Akt, glycogen synthase kinase-3beta and FKHR (forkhead transcription factor), was also enhanced by 2- and 2.9-fold, respectively. |
| 628 | 15734849 | The defects were accompanied by reduced mRNA expression of GLUT1 and -2 and glucokinase and by diminished glucose oxidation. |
| 629 | 15734849 | Furthermore, the expression of insulin was decreased, and that of pancreatic duodenal homeobox-1 (PDX-1) and forkhead box O1 (Foxo-1) was increased. |
| 630 | 15827066 | Insulin and IGF-I activate antiapoptotic pathways via insulin receptor substrate (IRS) proteins in most mammalian cells, including beta-cells. |
| 631 | 15827066 | IRS-1 knockout (IRS-1KO) mice show growth retardation, hyperinsulinemia, and hyperplastic but dysfunctional islets without developing overt diabetes, whereas IRS-2KOs develop insulin resistance and islet hypoplasia leading to diabetes. |
| 632 | 15827066 | We used a transplantation approach, as a means of separating host insulin resistance from islet function, to examine alterations in proteins in insulin/IGF-I signaling pathways that may contribute to beta-cell proliferation and/or apoptosis in IRS-1KO islets. |
| 633 | 15827066 | Furthermore, enhanced cytosolic forkhead transcription factor (FoxO1) staining in IRS-1KO grafts suggests intact Akt/PKB activity. |
| 634 | 15827066 | Together, these data indicate that, even in the absence of insulin resistance, beta-cells deficient in IRS-1 exhibit a compensatory increase in IRS-2, which is associated with islet growth and is characterized by both proliferative and antiapoptotic effects that likely occur via an insulin/IGF-I/IRS-2 pathway. |
| 635 | 15890677 | The coactivator p300 directly acetylates the forkhead transcription factor Foxo1 and stimulates Foxo1-induced transcription. |
| 636 | 15890677 | In this report, we show that the coactivator p300 directly acetylates lysines in the carboxyl-terminal region of Foxo1 in vivo and in vitro, and potently stimulates Foxo1-induced transcription of IGF-binding protein-1 in transient transfection experiments. |
| 637 | 15890677 | Our results suggest that acetylation of Foxo1 by p300 is responsible, at least in part, for its increased transactivation potency, although acetylation of histones cannot be excluded. |
| 638 | 15890677 | Insulin, the major negative regulator of Foxo1-stimulated transcription, potently enhances p300 acetylation of Foxo1. |
| 639 | 15890677 | Three consensus protein kinase B/Akt phosphorylation sites whose phosphorylation is stimulated by insulin are required for insulin-induced acetylation of Foxo1. |
| 640 | 15890677 | 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. |
| 641 | 15890677 | The coactivator p300 directly acetylates the forkhead transcription factor Foxo1 and stimulates Foxo1-induced transcription. |
| 642 | 15890677 | In this report, we show that the coactivator p300 directly acetylates lysines in the carboxyl-terminal region of Foxo1 in vivo and in vitro, and potently stimulates Foxo1-induced transcription of IGF-binding protein-1 in transient transfection experiments. |
| 643 | 15890677 | Our results suggest that acetylation of Foxo1 by p300 is responsible, at least in part, for its increased transactivation potency, although acetylation of histones cannot be excluded. |
| 644 | 15890677 | Insulin, the major negative regulator of Foxo1-stimulated transcription, potently enhances p300 acetylation of Foxo1. |
| 645 | 15890677 | Three consensus protein kinase B/Akt phosphorylation sites whose phosphorylation is stimulated by insulin are required for insulin-induced acetylation of Foxo1. |
| 646 | 15890677 | 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. |
| 647 | 15890677 | The coactivator p300 directly acetylates the forkhead transcription factor Foxo1 and stimulates Foxo1-induced transcription. |
| 648 | 15890677 | In this report, we show that the coactivator p300 directly acetylates lysines in the carboxyl-terminal region of Foxo1 in vivo and in vitro, and potently stimulates Foxo1-induced transcription of IGF-binding protein-1 in transient transfection experiments. |
| 649 | 15890677 | Our results suggest that acetylation of Foxo1 by p300 is responsible, at least in part, for its increased transactivation potency, although acetylation of histones cannot be excluded. |
| 650 | 15890677 | Insulin, the major negative regulator of Foxo1-stimulated transcription, potently enhances p300 acetylation of Foxo1. |
| 651 | 15890677 | Three consensus protein kinase B/Akt phosphorylation sites whose phosphorylation is stimulated by insulin are required for insulin-induced acetylation of Foxo1. |
| 652 | 15890677 | 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. |
| 653 | 15890677 | The coactivator p300 directly acetylates the forkhead transcription factor Foxo1 and stimulates Foxo1-induced transcription. |
| 654 | 15890677 | In this report, we show that the coactivator p300 directly acetylates lysines in the carboxyl-terminal region of Foxo1 in vivo and in vitro, and potently stimulates Foxo1-induced transcription of IGF-binding protein-1 in transient transfection experiments. |
| 655 | 15890677 | Our results suggest that acetylation of Foxo1 by p300 is responsible, at least in part, for its increased transactivation potency, although acetylation of histones cannot be excluded. |
| 656 | 15890677 | Insulin, the major negative regulator of Foxo1-stimulated transcription, potently enhances p300 acetylation of Foxo1. |
| 657 | 15890677 | Three consensus protein kinase B/Akt phosphorylation sites whose phosphorylation is stimulated by insulin are required for insulin-induced acetylation of Foxo1. |
| 658 | 15890677 | 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. |
| 659 | 15890677 | The coactivator p300 directly acetylates the forkhead transcription factor Foxo1 and stimulates Foxo1-induced transcription. |
| 660 | 15890677 | In this report, we show that the coactivator p300 directly acetylates lysines in the carboxyl-terminal region of Foxo1 in vivo and in vitro, and potently stimulates Foxo1-induced transcription of IGF-binding protein-1 in transient transfection experiments. |
| 661 | 15890677 | Our results suggest that acetylation of Foxo1 by p300 is responsible, at least in part, for its increased transactivation potency, although acetylation of histones cannot be excluded. |
| 662 | 15890677 | Insulin, the major negative regulator of Foxo1-stimulated transcription, potently enhances p300 acetylation of Foxo1. |
| 663 | 15890677 | Three consensus protein kinase B/Akt phosphorylation sites whose phosphorylation is stimulated by insulin are required for insulin-induced acetylation of Foxo1. |
| 664 | 15890677 | 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. |
| 665 | 15890677 | The coactivator p300 directly acetylates the forkhead transcription factor Foxo1 and stimulates Foxo1-induced transcription. |
| 666 | 15890677 | In this report, we show that the coactivator p300 directly acetylates lysines in the carboxyl-terminal region of Foxo1 in vivo and in vitro, and potently stimulates Foxo1-induced transcription of IGF-binding protein-1 in transient transfection experiments. |
| 667 | 15890677 | Our results suggest that acetylation of Foxo1 by p300 is responsible, at least in part, for its increased transactivation potency, although acetylation of histones cannot be excluded. |
| 668 | 15890677 | Insulin, the major negative regulator of Foxo1-stimulated transcription, potently enhances p300 acetylation of Foxo1. |
| 669 | 15890677 | Three consensus protein kinase B/Akt phosphorylation sites whose phosphorylation is stimulated by insulin are required for insulin-induced acetylation of Foxo1. |
| 670 | 15890677 | 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. |
| 671 | 15910615 | Among the many molecules involved in the intracellular processing of the signal provided by insulin, insulin receptor substrate (IRS)-2, the protein kinase B (PKB)-beta isoform and the forkhead transcription factor Foxo1a (FKHR) are of particular interest in this context as recent data have provided strong evidence that dysfunction of these proteins results in insulin resistance in-vivo. |
| 672 | 16154098 | FoxO1 protects against pancreatic beta cell failure through NeuroD and MafA induction. |
| 673 | 16154098 | We show that the forkhead protein FoxO1 protects beta cells against oxidative stress by forming a complex with the promyelocytic leukemia protein Pml and the NAD-dependent deacetylase Sirt1 to activate expression of NeuroD and MafA, two Insulin2 (Ins2) gene transcription factors. |
| 674 | 16154098 | Using acetylation-defective and acetylation-mimicking mutants, we demonstrate that acetylation targets FoxO1 to Pml and prevents ubiquitin-dependent degradation. |
| 675 | 16154098 | We show that hyperglycemia suppresses MafA expression in vivo and that MafA inhibition can be prevented by transgenic expression of constitutively nuclear FoxO1 in beta cells. |
| 676 | 16154098 | FoxO1 protects against pancreatic beta cell failure through NeuroD and MafA induction. |
| 677 | 16154098 | We show that the forkhead protein FoxO1 protects beta cells against oxidative stress by forming a complex with the promyelocytic leukemia protein Pml and the NAD-dependent deacetylase Sirt1 to activate expression of NeuroD and MafA, two Insulin2 (Ins2) gene transcription factors. |
| 678 | 16154098 | Using acetylation-defective and acetylation-mimicking mutants, we demonstrate that acetylation targets FoxO1 to Pml and prevents ubiquitin-dependent degradation. |
| 679 | 16154098 | We show that hyperglycemia suppresses MafA expression in vivo and that MafA inhibition can be prevented by transgenic expression of constitutively nuclear FoxO1 in beta cells. |
| 680 | 16154098 | FoxO1 protects against pancreatic beta cell failure through NeuroD and MafA induction. |
| 681 | 16154098 | We show that the forkhead protein FoxO1 protects beta cells against oxidative stress by forming a complex with the promyelocytic leukemia protein Pml and the NAD-dependent deacetylase Sirt1 to activate expression of NeuroD and MafA, two Insulin2 (Ins2) gene transcription factors. |
| 682 | 16154098 | Using acetylation-defective and acetylation-mimicking mutants, we demonstrate that acetylation targets FoxO1 to Pml and prevents ubiquitin-dependent degradation. |
| 683 | 16154098 | We show that hyperglycemia suppresses MafA expression in vivo and that MafA inhibition can be prevented by transgenic expression of constitutively nuclear FoxO1 in beta cells. |
| 684 | 16154098 | FoxO1 protects against pancreatic beta cell failure through NeuroD and MafA induction. |
| 685 | 16154098 | We show that the forkhead protein FoxO1 protects beta cells against oxidative stress by forming a complex with the promyelocytic leukemia protein Pml and the NAD-dependent deacetylase Sirt1 to activate expression of NeuroD and MafA, two Insulin2 (Ins2) gene transcription factors. |
| 686 | 16154098 | Using acetylation-defective and acetylation-mimicking mutants, we demonstrate that acetylation targets FoxO1 to Pml and prevents ubiquitin-dependent degradation. |
| 687 | 16154098 | We show that hyperglycemia suppresses MafA expression in vivo and that MafA inhibition can be prevented by transgenic expression of constitutively nuclear FoxO1 in beta cells. |
| 688 | 16170201 | The Irs2 branch of the insulin/insulin-like growth factor signaling cascade activates the phosphatidylinositol 3-kinase --> Akt --> Foxo1 cascade in many tissues, including hepatocytes and pancreatic beta-cells. |
| 689 | 16170201 | To determine whether decreased Pten expression could restore beta-cell function and prevent diabetes in Irs2(-/-) mice, we generated wild type or Irs2 knock-out mice that were haploinsufficient for Pten (Irs2(-/-)::Pten(+/-)). |
| 690 | 16170201 | Irs2(-/-) mice develop diabetes by 3 months of age as beta-cell mass declined progressively until insulin production was lost. |
| 691 | 16170201 | Pten insufficiency increased peripheral insulin sensitivity in wild type and Irs2(-/-) mice and increased Akt and Foxo1 phosphorylation in the islets. |
| 692 | 16170201 | Glucose tolerance improved in the Pten(+/-) mice, although beta-cell mass and circulating insulin levels decreased. |
| 693 | 16170201 | Compared with Irs2(-/-) mice, the Irs2(-/-)::Pten(+/-) mice displayed nearly normal glucose tolerance and survived without diabetes, because normal but small islets produced sufficient insulin until the mice died of lymphoproliferative disease at 12 months age. |
| 694 | 16170201 | Thus, steps to enhance phosphatidylinositol 3-kinase signaling can promote beta-cell growth, function, and survival without the Irs2 branch of the insulin/insulin-like growth factor signaling cascade. |
| 695 | 16375695 | Insulin regulation of PEPCK gene expression: a model for rapid and reversible modulation. |
| 696 | 16375695 | Normally, PEPCK expression is induced by glucagon, catecholamines and glucocorticoids during periods of fasting and in response to stress, but is dominantly inhibited by glucose-induced increases in insulin secretion upon feeding. |
| 697 | 16375695 | Thus, defining a molecular mechanism for insulin inhibition of PEPCK gene transcription has been a major goal of research in several labs, because it would allow the development of drugs to prevent episodic increases in circulating glucose in diabetics. |
| 698 | 16375695 | Any mechanism must account for the rapidity, specificity and dominance with which insulin is known to act in regulating PEPCK transcription. |
| 699 | 16375695 | To date Foxo1 (FKHR) is the only transcription factor for which a complete path from the insulin receptor to gene regulation has been described. |
| 700 | 16375695 | While this explains the regulation of some genes, such as IGFBP-1, Foxo1 appears not to play a requisite role in regulating PEPCK transcription. |
| 701 | 16375695 | Investigation of cis-acting elements in the PEPCK promoter has shed considerable light on the mechanisms of activation by cAMP and glucocorticoids but has failed to identify a regulatory element that mediates insulin inhibition of transcription. |
| 702 | 16375695 | Insulin regulation of PEPCK gene expression: a model for rapid and reversible modulation. |
| 703 | 16375695 | Normally, PEPCK expression is induced by glucagon, catecholamines and glucocorticoids during periods of fasting and in response to stress, but is dominantly inhibited by glucose-induced increases in insulin secretion upon feeding. |
| 704 | 16375695 | Thus, defining a molecular mechanism for insulin inhibition of PEPCK gene transcription has been a major goal of research in several labs, because it would allow the development of drugs to prevent episodic increases in circulating glucose in diabetics. |
| 705 | 16375695 | Any mechanism must account for the rapidity, specificity and dominance with which insulin is known to act in regulating PEPCK transcription. |
| 706 | 16375695 | To date Foxo1 (FKHR) is the only transcription factor for which a complete path from the insulin receptor to gene regulation has been described. |
| 707 | 16375695 | While this explains the regulation of some genes, such as IGFBP-1, Foxo1 appears not to play a requisite role in regulating PEPCK transcription. |
| 708 | 16375695 | Investigation of cis-acting elements in the PEPCK promoter has shed considerable light on the mechanisms of activation by cAMP and glucocorticoids but has failed to identify a regulatory element that mediates insulin inhibition of transcription. |
| 709 | 16485043 | Role of the forkhead protein FoxO1 in beta cell compensation to insulin resistance. |
| 710 | 16485043 | We show that the mutant FoxO1 transgene prevents beta cell replication in 2 models of beta cell hyperplasia, 1 due to peripheral insulin resistance (Insulin receptor transgenic knockouts) and 1 due to ectopic local expression of IGF2 (Elastase-IGF2 transgenics), without affecting insulin secretion. |
| 711 | 16485043 | We propose that beta cell compensation to insulin resistance is a proliferative response of existing beta cells to growth factor signaling and requires FoxO1 nuclear exclusion. |
| 712 | 16485043 | Role of the forkhead protein FoxO1 in beta cell compensation to insulin resistance. |
| 713 | 16485043 | We show that the mutant FoxO1 transgene prevents beta cell replication in 2 models of beta cell hyperplasia, 1 due to peripheral insulin resistance (Insulin receptor transgenic knockouts) and 1 due to ectopic local expression of IGF2 (Elastase-IGF2 transgenics), without affecting insulin secretion. |
| 714 | 16485043 | We propose that beta cell compensation to insulin resistance is a proliferative response of existing beta cells to growth factor signaling and requires FoxO1 nuclear exclusion. |
| 715 | 16485043 | Role of the forkhead protein FoxO1 in beta cell compensation to insulin resistance. |
| 716 | 16485043 | We show that the mutant FoxO1 transgene prevents beta cell replication in 2 models of beta cell hyperplasia, 1 due to peripheral insulin resistance (Insulin receptor transgenic knockouts) and 1 due to ectopic local expression of IGF2 (Elastase-IGF2 transgenics), without affecting insulin secretion. |
| 717 | 16485043 | We propose that beta cell compensation to insulin resistance is a proliferative response of existing beta cells to growth factor signaling and requires FoxO1 nuclear exclusion. |
| 718 | 16497530 | The human forkhead box O1A (FOXO1A) gene on chromosome 13q14.1 is a key transcription factor in insulin signaling in liver and adipose tissue and plays a central role in the regulation of key pancreatic beta-cell genes including IPF1. |
| 719 | 16497530 | We hypothesized that sequence variants of FOXO1A contribute to the observed defects in hepatic and peripheral insulin action and altered beta-cell compensation that characterize type 2 diabetes (T2DM). |
| 720 | 16497530 | The human forkhead box O1A (FOXO1A) gene on chromosome 13q14.1 is a key transcription factor in insulin signaling in liver and adipose tissue and plays a central role in the regulation of key pancreatic beta-cell genes including IPF1. |
| 721 | 16497530 | We hypothesized that sequence variants of FOXO1A contribute to the observed defects in hepatic and peripheral insulin action and altered beta-cell compensation that characterize type 2 diabetes (T2DM). |
| 722 | 16604193 | Renal expression of several genes that encode proteins associated with senescence and/or apoptosis (TGF-beta1, connective tissue growth factor, p53, alpha-synuclein, and forkhead box O1) increases in the same progression. |
| 723 | 16644672 | The glucoincretin hormone glucagon-like peptide-1 (GLP-1) increases pancreatic beta-cell proliferation and survival through sequential activation of the epidermal growth factor receptor (EGFR), phosphatidylinositol-3 kinase (PI 3-kinase), and Akt. |
| 724 | 16644672 | GLP-1 inhibited FoxO1 through phosphorylation-dependent nuclear exclusion in pancreatic beta (INS832/13) cells. |
| 725 | 16644672 | The effect of GLP-1 was suppressed by inhibitors of EGFR (AG1478) and PI 3-kinase (LY294002). |
| 726 | 16644672 | Gene expression and chromatin immunoprecipitation assays demonstrated that GLP-1 increases pancreatic and duodenal homeobox gene-1 and Foxa2 expression and inhibits FoxO1 binding to both promoters. |
| 727 | 16804074 | The transcription factor Foxo1 links insulin signaling to decreased transcription of PEPCK and glucose-6-phosphatase (G6Pase) and provides a possible therapeutic target in insulin-resistant states. |
| 728 | 16804074 | In mice with DIO and insulin resistance, Foxo1 ASO therapy lowered plasma glucose concentration and the rate of basal endogenous glucose production. |
| 729 | 16804074 | In addition, Foxo1 ASO therapy lowered both hepatic triglyceride and diacylglycerol content and improved hepatic insulin sensitivity. |
| 730 | 16804074 | Foxo1 ASO also improved adipocyte insulin action. |
| 731 | 16804074 | In conclusion, Foxo1 ASO therapy improved both hepatic insulin and peripheral insulin action. |
| 732 | 16804074 | Foxo1 is a potential therapeutic target for improving insulin resistance. |
| 733 | 16804074 | The transcription factor Foxo1 links insulin signaling to decreased transcription of PEPCK and glucose-6-phosphatase (G6Pase) and provides a possible therapeutic target in insulin-resistant states. |
| 734 | 16804074 | In mice with DIO and insulin resistance, Foxo1 ASO therapy lowered plasma glucose concentration and the rate of basal endogenous glucose production. |
| 735 | 16804074 | In addition, Foxo1 ASO therapy lowered both hepatic triglyceride and diacylglycerol content and improved hepatic insulin sensitivity. |
| 736 | 16804074 | Foxo1 ASO also improved adipocyte insulin action. |
| 737 | 16804074 | In conclusion, Foxo1 ASO therapy improved both hepatic insulin and peripheral insulin action. |
| 738 | 16804074 | Foxo1 is a potential therapeutic target for improving insulin resistance. |
| 739 | 16804074 | The transcription factor Foxo1 links insulin signaling to decreased transcription of PEPCK and glucose-6-phosphatase (G6Pase) and provides a possible therapeutic target in insulin-resistant states. |
| 740 | 16804074 | In mice with DIO and insulin resistance, Foxo1 ASO therapy lowered plasma glucose concentration and the rate of basal endogenous glucose production. |
| 741 | 16804074 | In addition, Foxo1 ASO therapy lowered both hepatic triglyceride and diacylglycerol content and improved hepatic insulin sensitivity. |
| 742 | 16804074 | Foxo1 ASO also improved adipocyte insulin action. |
| 743 | 16804074 | In conclusion, Foxo1 ASO therapy improved both hepatic insulin and peripheral insulin action. |
| 744 | 16804074 | Foxo1 is a potential therapeutic target for improving insulin resistance. |
| 745 | 16804074 | The transcription factor Foxo1 links insulin signaling to decreased transcription of PEPCK and glucose-6-phosphatase (G6Pase) and provides a possible therapeutic target in insulin-resistant states. |
| 746 | 16804074 | In mice with DIO and insulin resistance, Foxo1 ASO therapy lowered plasma glucose concentration and the rate of basal endogenous glucose production. |
| 747 | 16804074 | In addition, Foxo1 ASO therapy lowered both hepatic triglyceride and diacylglycerol content and improved hepatic insulin sensitivity. |
| 748 | 16804074 | Foxo1 ASO also improved adipocyte insulin action. |
| 749 | 16804074 | In conclusion, Foxo1 ASO therapy improved both hepatic insulin and peripheral insulin action. |
| 750 | 16804074 | Foxo1 is a potential therapeutic target for improving insulin resistance. |
| 751 | 16804074 | The transcription factor Foxo1 links insulin signaling to decreased transcription of PEPCK and glucose-6-phosphatase (G6Pase) and provides a possible therapeutic target in insulin-resistant states. |
| 752 | 16804074 | In mice with DIO and insulin resistance, Foxo1 ASO therapy lowered plasma glucose concentration and the rate of basal endogenous glucose production. |
| 753 | 16804074 | In addition, Foxo1 ASO therapy lowered both hepatic triglyceride and diacylglycerol content and improved hepatic insulin sensitivity. |
| 754 | 16804074 | Foxo1 ASO also improved adipocyte insulin action. |
| 755 | 16804074 | In conclusion, Foxo1 ASO therapy improved both hepatic insulin and peripheral insulin action. |
| 756 | 16804074 | Foxo1 is a potential therapeutic target for improving insulin resistance. |
| 757 | 16804074 | The transcription factor Foxo1 links insulin signaling to decreased transcription of PEPCK and glucose-6-phosphatase (G6Pase) and provides a possible therapeutic target in insulin-resistant states. |
| 758 | 16804074 | In mice with DIO and insulin resistance, Foxo1 ASO therapy lowered plasma glucose concentration and the rate of basal endogenous glucose production. |
| 759 | 16804074 | In addition, Foxo1 ASO therapy lowered both hepatic triglyceride and diacylglycerol content and improved hepatic insulin sensitivity. |
| 760 | 16804074 | Foxo1 ASO also improved adipocyte insulin action. |
| 761 | 16804074 | In conclusion, Foxo1 ASO therapy improved both hepatic insulin and peripheral insulin action. |
| 762 | 16804074 | Foxo1 is a potential therapeutic target for improving insulin resistance. |
| 763 | 16865227 | The nutrient response mediated by feeding or fasting plays an important role in controlling gluconeogenic gene expression such as glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxylase (PEPCK). |
| 764 | 16865227 | The FOXO family of forkhead transcription factor Foxo1 (mouse FOXO1) is a key regulator that stimulates the expression of gluconeogenic genes in the nucleus but is phosphorylated by Akt (also known as protein kinase B; PKB) and translocated to the cytoplasm in response to insulin. |
| 765 | 16865227 | Although it has been widely accepted that the cellular signaling of insulin represses Foxo1 function through Akt-dependent phosphorylation, the molecular mechanism behind the modulation of Foxo1 function by nutrient responses, including feeding or fasting, remains unknown in vivo. |
| 766 | 16865227 | Notably, db/db mice exhibited constitutive phosphorylation but dominant nuclear accumulation of Foxo1, even though CREB phosphorylation usually occurred in the fasted status. |
| 767 | 16865227 | Furthermore, in contrast to C57BL/6 mice, the expression of G6Pase, PEPCK and PGC-1alpha genes during feeding was not down-regulated in db/db mice. |
| 768 | 16865227 | The nutrient response mediated by feeding or fasting plays an important role in controlling gluconeogenic gene expression such as glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxylase (PEPCK). |
| 769 | 16865227 | The FOXO family of forkhead transcription factor Foxo1 (mouse FOXO1) is a key regulator that stimulates the expression of gluconeogenic genes in the nucleus but is phosphorylated by Akt (also known as protein kinase B; PKB) and translocated to the cytoplasm in response to insulin. |
| 770 | 16865227 | Although it has been widely accepted that the cellular signaling of insulin represses Foxo1 function through Akt-dependent phosphorylation, the molecular mechanism behind the modulation of Foxo1 function by nutrient responses, including feeding or fasting, remains unknown in vivo. |
| 771 | 16865227 | Notably, db/db mice exhibited constitutive phosphorylation but dominant nuclear accumulation of Foxo1, even though CREB phosphorylation usually occurred in the fasted status. |
| 772 | 16865227 | Furthermore, in contrast to C57BL/6 mice, the expression of G6Pase, PEPCK and PGC-1alpha genes during feeding was not down-regulated in db/db mice. |
| 773 | 16865227 | The nutrient response mediated by feeding or fasting plays an important role in controlling gluconeogenic gene expression such as glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxylase (PEPCK). |
| 774 | 16865227 | The FOXO family of forkhead transcription factor Foxo1 (mouse FOXO1) is a key regulator that stimulates the expression of gluconeogenic genes in the nucleus but is phosphorylated by Akt (also known as protein kinase B; PKB) and translocated to the cytoplasm in response to insulin. |
| 775 | 16865227 | Although it has been widely accepted that the cellular signaling of insulin represses Foxo1 function through Akt-dependent phosphorylation, the molecular mechanism behind the modulation of Foxo1 function by nutrient responses, including feeding or fasting, remains unknown in vivo. |
| 776 | 16865227 | Notably, db/db mice exhibited constitutive phosphorylation but dominant nuclear accumulation of Foxo1, even though CREB phosphorylation usually occurred in the fasted status. |
| 777 | 16865227 | Furthermore, in contrast to C57BL/6 mice, the expression of G6Pase, PEPCK and PGC-1alpha genes during feeding was not down-regulated in db/db mice. |
| 778 | 16870142 | Insulin suppressed angptl4 mRNA expression in time- and dose-dependent manners, and the inhibitory effect was attenuated by a RNA synthesis inhibitor actinomycin D and a phosphoinositide 3-kinase (PI3K) inhibitor LY294002. |
| 779 | 16870142 | Adenoviral-mediated overexpression of forkhead transcription factor Foxo1 increased angptl4 mRNA expression, and insulin significantly suppressed its effect. |
| 780 | 16870142 | In addition, insulin failed to decrease angptl4 mRNA expression in an insulin-resistant state induced by TNF-alpha in 3T3-L1 adipocytes. |
| 781 | 16870142 | These results suggest that insulin downregulates angptl4 mRNA expression via PI3K/Foxo1 pathway in 3T3-L1 adipocytes, and that the reduction of angptl4 mRNA by insulin is attenuated in insulin resistance. |
| 782 | 16870142 | Insulin suppressed angptl4 mRNA expression in time- and dose-dependent manners, and the inhibitory effect was attenuated by a RNA synthesis inhibitor actinomycin D and a phosphoinositide 3-kinase (PI3K) inhibitor LY294002. |
| 783 | 16870142 | Adenoviral-mediated overexpression of forkhead transcription factor Foxo1 increased angptl4 mRNA expression, and insulin significantly suppressed its effect. |
| 784 | 16870142 | In addition, insulin failed to decrease angptl4 mRNA expression in an insulin-resistant state induced by TNF-alpha in 3T3-L1 adipocytes. |
| 785 | 16870142 | These results suggest that insulin downregulates angptl4 mRNA expression via PI3K/Foxo1 pathway in 3T3-L1 adipocytes, and that the reduction of angptl4 mRNA by insulin is attenuated in insulin resistance. |
| 786 | 16873685 | Morphological analysis revealed that high glucose significantly affected the number of endothelial cell colony forming units, uptake and binding of acLDL and Lectin-1, and the ability to differentiate into CD31- and vascular endothelial growth factor receptor 2-positive cells. |
| 787 | 16873685 | Our results indicate that hyperglycemia impairs EPC differentiation and that the process can be restored by benfotiamine administration, via the modulation of Akt/FoxO1 activity. |
| 788 | 16873695 | Insulin regulation of skeletal muscle PDK4 mRNA expression is impaired in acute insulin-resistant states. |
| 789 | 16873695 | We previously showed that insulin has a profound effect to suppress pyruvate dehydrogenase kinase (PDK) 4 expression in rat skeletal muscle. |
| 790 | 16873695 | In the present study, we examined whether insulin's effect on PDK4 expression is impaired in acute insulin-resistant states and, if so, whether this change is accompanied by decreased insulin's effects to stimulate Akt and forkhead box class O (FOXO) 1 phosphorylation. |
| 791 | 16873695 | Insulin's ability to suppress PDK4 mRNA level was impaired in skeletal muscle with Intralipid and lactate infusions, resulting in two- to threefold higher PDK4 mRNA levels with insulin (P < 0.05). |
| 792 | 16873695 | Insulin stimulation of Akt and FOXO1 phosphorylation was also significantly decreased with Intralipid and lactate infusions. |
| 793 | 16873695 | These data suggest that insulin's effect to suppress PDK4 gene expression in skeletal muscle is impaired in insulin-resistant states, and this may be due to impaired insulin signaling for stimulation of Akt and FOXO1 phosphorylation. |
| 794 | 16873695 | Impaired insulin's effect to suppress PDK4 expression may explain the association between PDK4 overexpression and insulin resistance in skeletal muscle. |
| 795 | 16873695 | Insulin regulation of skeletal muscle PDK4 mRNA expression is impaired in acute insulin-resistant states. |
| 796 | 16873695 | We previously showed that insulin has a profound effect to suppress pyruvate dehydrogenase kinase (PDK) 4 expression in rat skeletal muscle. |
| 797 | 16873695 | In the present study, we examined whether insulin's effect on PDK4 expression is impaired in acute insulin-resistant states and, if so, whether this change is accompanied by decreased insulin's effects to stimulate Akt and forkhead box class O (FOXO) 1 phosphorylation. |
| 798 | 16873695 | Insulin's ability to suppress PDK4 mRNA level was impaired in skeletal muscle with Intralipid and lactate infusions, resulting in two- to threefold higher PDK4 mRNA levels with insulin (P < 0.05). |
| 799 | 16873695 | Insulin stimulation of Akt and FOXO1 phosphorylation was also significantly decreased with Intralipid and lactate infusions. |
| 800 | 16873695 | These data suggest that insulin's effect to suppress PDK4 gene expression in skeletal muscle is impaired in insulin-resistant states, and this may be due to impaired insulin signaling for stimulation of Akt and FOXO1 phosphorylation. |
| 801 | 16873695 | Impaired insulin's effect to suppress PDK4 expression may explain the association between PDK4 overexpression and insulin resistance in skeletal muscle. |
| 802 | 16885156 | Insulin regulation of cholesterol 7alpha-hydroxylase expression in human hepatocytes: roles of forkhead box O1 and sterol regulatory element-binding protein 1c. |
| 803 | 16885156 | Real-time PCR assays showed that physiological concentrations of insulin rapidly stimulated cholesterol 7alpha-hydroxylase (CYP7A1) mRNA expression in primary human hepatocytes but inhibited CYP7A1 expression after extended treatment. |
| 804 | 16885156 | The insulin-regulated forkhead box O1 (FoxO1) and steroid regulatory element-binding protein-1c (SREBP-1c) strongly inhibited hepatocyte nuclear factor 4alpha and peroxisome proliferator-activated receptor gamma coactivator-1alpha trans-activation of the CYP7A1 gene. |
| 805 | 16885156 | FoxO1 binds to an insulin response element in the rat CYP7A1 promoter, which is not present in the human CYP7A1 gene. |
| 806 | 16885156 | Insulin rapidly phosphorylates and inactivates FoxO1, whereas insulin induces nuclear SREBP-1c expression in human primary hepatocytes. |
| 807 | 16885156 | Chromatin immunoprecipitation assay shows that insulin reduced FoxO1 and peroxisome proliferators-activated receptor gamma-coactivator-1alpha but increased SREBP-1c recruitment to CYP7A1 chromatin. |
| 808 | 16885156 | We conclude that insulin has dual effects on human CYP7A1 gene transcription; physiological concentrations of insulin rapidly inhibit FoxO1 activity leading to stimulation of the human CYP7A1 gene, whereas prolonged insulin treatment induces SREBP-1c, which inhibits human CYP7A1 gene transcription. |
| 809 | 16885156 | Insulin regulation of cholesterol 7alpha-hydroxylase expression in human hepatocytes: roles of forkhead box O1 and sterol regulatory element-binding protein 1c. |
| 810 | 16885156 | Real-time PCR assays showed that physiological concentrations of insulin rapidly stimulated cholesterol 7alpha-hydroxylase (CYP7A1) mRNA expression in primary human hepatocytes but inhibited CYP7A1 expression after extended treatment. |
| 811 | 16885156 | The insulin-regulated forkhead box O1 (FoxO1) and steroid regulatory element-binding protein-1c (SREBP-1c) strongly inhibited hepatocyte nuclear factor 4alpha and peroxisome proliferator-activated receptor gamma coactivator-1alpha trans-activation of the CYP7A1 gene. |
| 812 | 16885156 | FoxO1 binds to an insulin response element in the rat CYP7A1 promoter, which is not present in the human CYP7A1 gene. |
| 813 | 16885156 | Insulin rapidly phosphorylates and inactivates FoxO1, whereas insulin induces nuclear SREBP-1c expression in human primary hepatocytes. |
| 814 | 16885156 | Chromatin immunoprecipitation assay shows that insulin reduced FoxO1 and peroxisome proliferators-activated receptor gamma-coactivator-1alpha but increased SREBP-1c recruitment to CYP7A1 chromatin. |
| 815 | 16885156 | We conclude that insulin has dual effects on human CYP7A1 gene transcription; physiological concentrations of insulin rapidly inhibit FoxO1 activity leading to stimulation of the human CYP7A1 gene, whereas prolonged insulin treatment induces SREBP-1c, which inhibits human CYP7A1 gene transcription. |
| 816 | 16885156 | Insulin regulation of cholesterol 7alpha-hydroxylase expression in human hepatocytes: roles of forkhead box O1 and sterol regulatory element-binding protein 1c. |
| 817 | 16885156 | Real-time PCR assays showed that physiological concentrations of insulin rapidly stimulated cholesterol 7alpha-hydroxylase (CYP7A1) mRNA expression in primary human hepatocytes but inhibited CYP7A1 expression after extended treatment. |
| 818 | 16885156 | The insulin-regulated forkhead box O1 (FoxO1) and steroid regulatory element-binding protein-1c (SREBP-1c) strongly inhibited hepatocyte nuclear factor 4alpha and peroxisome proliferator-activated receptor gamma coactivator-1alpha trans-activation of the CYP7A1 gene. |
| 819 | 16885156 | FoxO1 binds to an insulin response element in the rat CYP7A1 promoter, which is not present in the human CYP7A1 gene. |
| 820 | 16885156 | Insulin rapidly phosphorylates and inactivates FoxO1, whereas insulin induces nuclear SREBP-1c expression in human primary hepatocytes. |
| 821 | 16885156 | Chromatin immunoprecipitation assay shows that insulin reduced FoxO1 and peroxisome proliferators-activated receptor gamma-coactivator-1alpha but increased SREBP-1c recruitment to CYP7A1 chromatin. |
| 822 | 16885156 | We conclude that insulin has dual effects on human CYP7A1 gene transcription; physiological concentrations of insulin rapidly inhibit FoxO1 activity leading to stimulation of the human CYP7A1 gene, whereas prolonged insulin treatment induces SREBP-1c, which inhibits human CYP7A1 gene transcription. |
| 823 | 16885156 | Insulin regulation of cholesterol 7alpha-hydroxylase expression in human hepatocytes: roles of forkhead box O1 and sterol regulatory element-binding protein 1c. |
| 824 | 16885156 | Real-time PCR assays showed that physiological concentrations of insulin rapidly stimulated cholesterol 7alpha-hydroxylase (CYP7A1) mRNA expression in primary human hepatocytes but inhibited CYP7A1 expression after extended treatment. |
| 825 | 16885156 | The insulin-regulated forkhead box O1 (FoxO1) and steroid regulatory element-binding protein-1c (SREBP-1c) strongly inhibited hepatocyte nuclear factor 4alpha and peroxisome proliferator-activated receptor gamma coactivator-1alpha trans-activation of the CYP7A1 gene. |
| 826 | 16885156 | FoxO1 binds to an insulin response element in the rat CYP7A1 promoter, which is not present in the human CYP7A1 gene. |
| 827 | 16885156 | Insulin rapidly phosphorylates and inactivates FoxO1, whereas insulin induces nuclear SREBP-1c expression in human primary hepatocytes. |
| 828 | 16885156 | Chromatin immunoprecipitation assay shows that insulin reduced FoxO1 and peroxisome proliferators-activated receptor gamma-coactivator-1alpha but increased SREBP-1c recruitment to CYP7A1 chromatin. |
| 829 | 16885156 | We conclude that insulin has dual effects on human CYP7A1 gene transcription; physiological concentrations of insulin rapidly inhibit FoxO1 activity leading to stimulation of the human CYP7A1 gene, whereas prolonged insulin treatment induces SREBP-1c, which inhibits human CYP7A1 gene transcription. |
| 830 | 16885156 | Insulin regulation of cholesterol 7alpha-hydroxylase expression in human hepatocytes: roles of forkhead box O1 and sterol regulatory element-binding protein 1c. |
| 831 | 16885156 | Real-time PCR assays showed that physiological concentrations of insulin rapidly stimulated cholesterol 7alpha-hydroxylase (CYP7A1) mRNA expression in primary human hepatocytes but inhibited CYP7A1 expression after extended treatment. |
| 832 | 16885156 | The insulin-regulated forkhead box O1 (FoxO1) and steroid regulatory element-binding protein-1c (SREBP-1c) strongly inhibited hepatocyte nuclear factor 4alpha and peroxisome proliferator-activated receptor gamma coactivator-1alpha trans-activation of the CYP7A1 gene. |
| 833 | 16885156 | FoxO1 binds to an insulin response element in the rat CYP7A1 promoter, which is not present in the human CYP7A1 gene. |
| 834 | 16885156 | Insulin rapidly phosphorylates and inactivates FoxO1, whereas insulin induces nuclear SREBP-1c expression in human primary hepatocytes. |
| 835 | 16885156 | Chromatin immunoprecipitation assay shows that insulin reduced FoxO1 and peroxisome proliferators-activated receptor gamma-coactivator-1alpha but increased SREBP-1c recruitment to CYP7A1 chromatin. |
| 836 | 16885156 | We conclude that insulin has dual effects on human CYP7A1 gene transcription; physiological concentrations of insulin rapidly inhibit FoxO1 activity leading to stimulation of the human CYP7A1 gene, whereas prolonged insulin treatment induces SREBP-1c, which inhibits human CYP7A1 gene transcription. |
| 837 | 16885156 | Insulin regulation of cholesterol 7alpha-hydroxylase expression in human hepatocytes: roles of forkhead box O1 and sterol regulatory element-binding protein 1c. |
| 838 | 16885156 | Real-time PCR assays showed that physiological concentrations of insulin rapidly stimulated cholesterol 7alpha-hydroxylase (CYP7A1) mRNA expression in primary human hepatocytes but inhibited CYP7A1 expression after extended treatment. |
| 839 | 16885156 | The insulin-regulated forkhead box O1 (FoxO1) and steroid regulatory element-binding protein-1c (SREBP-1c) strongly inhibited hepatocyte nuclear factor 4alpha and peroxisome proliferator-activated receptor gamma coactivator-1alpha trans-activation of the CYP7A1 gene. |
| 840 | 16885156 | FoxO1 binds to an insulin response element in the rat CYP7A1 promoter, which is not present in the human CYP7A1 gene. |
| 841 | 16885156 | Insulin rapidly phosphorylates and inactivates FoxO1, whereas insulin induces nuclear SREBP-1c expression in human primary hepatocytes. |
| 842 | 16885156 | Chromatin immunoprecipitation assay shows that insulin reduced FoxO1 and peroxisome proliferators-activated receptor gamma-coactivator-1alpha but increased SREBP-1c recruitment to CYP7A1 chromatin. |
| 843 | 16885156 | We conclude that insulin has dual effects on human CYP7A1 gene transcription; physiological concentrations of insulin rapidly inhibit FoxO1 activity leading to stimulation of the human CYP7A1 gene, whereas prolonged insulin treatment induces SREBP-1c, which inhibits human CYP7A1 gene transcription. |
| 844 | 16917544 | The forkhead transcription factor FoxO1 has been identified as a negative regulator of insulin/IGF-1 signaling. |
| 845 | 16917544 | Expression of a 3A/LXXAA mutant, in which 3 Akt phosphorylation sites (T24, S253, and S316) and 2 leucine residues in the LXXLL motif (L462 and L463) were replaced by alanine, decreased both Igfbp-1 and G6Pase promoter activity and endogenous Igfbp-1 and G6Pase gene expression in simian virus 40-transformed (SV40-transformed) hepatocytes. |
| 846 | 16917544 | Importantly, mutagenesis of the LXXLL motif eliminated FoxO1 interaction with the nicotinamide adenine dinucleotide-dependent (NAD-dependent) deacetylase sirtuin 1 (Sirt1), sustained the acetylated state of FoxO1, and made FoxO1 nicotinamide and resveratrol insensitive, supporting a role for this motif in Sirt1 binding. |
| 847 | 16917544 | Furthermore, intravenous administration of adenovirus encoding 3A/LXXAA FoxO1 into Lepr db/db mice decreased fasting blood glucose levels and improved glucose tolerance and was accompanied by reduced G6Pase and Igfbp-1 gene expression and increased hepatic glycogen content. |
| 848 | 16917544 | In conclusion, the LXXLL motif of FoxO1 may have an important role for its transcriptional activity and Sirt1 binding and should be a target site for regulation of gene expression of FoxO1 target genes and glucose metabolism in vivo. |
| 849 | 16917544 | The forkhead transcription factor FoxO1 has been identified as a negative regulator of insulin/IGF-1 signaling. |
| 850 | 16917544 | Expression of a 3A/LXXAA mutant, in which 3 Akt phosphorylation sites (T24, S253, and S316) and 2 leucine residues in the LXXLL motif (L462 and L463) were replaced by alanine, decreased both Igfbp-1 and G6Pase promoter activity and endogenous Igfbp-1 and G6Pase gene expression in simian virus 40-transformed (SV40-transformed) hepatocytes. |
| 851 | 16917544 | Importantly, mutagenesis of the LXXLL motif eliminated FoxO1 interaction with the nicotinamide adenine dinucleotide-dependent (NAD-dependent) deacetylase sirtuin 1 (Sirt1), sustained the acetylated state of FoxO1, and made FoxO1 nicotinamide and resveratrol insensitive, supporting a role for this motif in Sirt1 binding. |
| 852 | 16917544 | Furthermore, intravenous administration of adenovirus encoding 3A/LXXAA FoxO1 into Lepr db/db mice decreased fasting blood glucose levels and improved glucose tolerance and was accompanied by reduced G6Pase and Igfbp-1 gene expression and increased hepatic glycogen content. |
| 853 | 16917544 | In conclusion, the LXXLL motif of FoxO1 may have an important role for its transcriptional activity and Sirt1 binding and should be a target site for regulation of gene expression of FoxO1 target genes and glucose metabolism in vivo. |
| 854 | 16917544 | The forkhead transcription factor FoxO1 has been identified as a negative regulator of insulin/IGF-1 signaling. |
| 855 | 16917544 | Expression of a 3A/LXXAA mutant, in which 3 Akt phosphorylation sites (T24, S253, and S316) and 2 leucine residues in the LXXLL motif (L462 and L463) were replaced by alanine, decreased both Igfbp-1 and G6Pase promoter activity and endogenous Igfbp-1 and G6Pase gene expression in simian virus 40-transformed (SV40-transformed) hepatocytes. |
| 856 | 16917544 | Importantly, mutagenesis of the LXXLL motif eliminated FoxO1 interaction with the nicotinamide adenine dinucleotide-dependent (NAD-dependent) deacetylase sirtuin 1 (Sirt1), sustained the acetylated state of FoxO1, and made FoxO1 nicotinamide and resveratrol insensitive, supporting a role for this motif in Sirt1 binding. |
| 857 | 16917544 | Furthermore, intravenous administration of adenovirus encoding 3A/LXXAA FoxO1 into Lepr db/db mice decreased fasting blood glucose levels and improved glucose tolerance and was accompanied by reduced G6Pase and Igfbp-1 gene expression and increased hepatic glycogen content. |
| 858 | 16917544 | In conclusion, the LXXLL motif of FoxO1 may have an important role for its transcriptional activity and Sirt1 binding and should be a target site for regulation of gene expression of FoxO1 target genes and glucose metabolism in vivo. |
| 859 | 16917544 | The forkhead transcription factor FoxO1 has been identified as a negative regulator of insulin/IGF-1 signaling. |
| 860 | 16917544 | Expression of a 3A/LXXAA mutant, in which 3 Akt phosphorylation sites (T24, S253, and S316) and 2 leucine residues in the LXXLL motif (L462 and L463) were replaced by alanine, decreased both Igfbp-1 and G6Pase promoter activity and endogenous Igfbp-1 and G6Pase gene expression in simian virus 40-transformed (SV40-transformed) hepatocytes. |
| 861 | 16917544 | Importantly, mutagenesis of the LXXLL motif eliminated FoxO1 interaction with the nicotinamide adenine dinucleotide-dependent (NAD-dependent) deacetylase sirtuin 1 (Sirt1), sustained the acetylated state of FoxO1, and made FoxO1 nicotinamide and resveratrol insensitive, supporting a role for this motif in Sirt1 binding. |
| 862 | 16917544 | Furthermore, intravenous administration of adenovirus encoding 3A/LXXAA FoxO1 into Lepr db/db mice decreased fasting blood glucose levels and improved glucose tolerance and was accompanied by reduced G6Pase and Igfbp-1 gene expression and increased hepatic glycogen content. |
| 863 | 16917544 | In conclusion, the LXXLL motif of FoxO1 may have an important role for its transcriptional activity and Sirt1 binding and should be a target site for regulation of gene expression of FoxO1 target genes and glucose metabolism in vivo. |
| 864 | 16926159 | Pyrrolidine dithiocarbamate inhibits interleukin-6 signaling through impaired STAT3 activation and association with transcriptional coactivators in hepatocytes. |
| 865 | 16926159 | Interleukin (IL)-6 is a proinflammatory cytokine that has been implicated in the expression of acute phase plasma proteins and hepatic insulin resistance through activation of the JAK/STAT3 pathway. |
| 866 | 16926159 | Here we show that treatment of cultured HepG2 hepatoma cells with PDTC inhibits IL-6-stimulated tyrosine phosphorylation and subsequent nuclear translocation of STAT3 in a dose- and time-dependent fashion. |
| 867 | 16926159 | Although STAT3 coprecipitated with heat-shock protein 90 (Hsp90) in control cells, coprecipitation of the two proteins was greatly reduced after PDTC treatment or after exposure to geldanamycin, an Hsp90 inhibitor. |
| 868 | 16926159 | As a result there was a decrease in IL-6-induced association of STAT3 with the transcriptional coactivators FOXO1a and C/EBPbeta together with significant reduction in the expression of SOCS-3 protein and that of two major acute phase plasma proteins. |
| 869 | 16926159 | Importantly, treatment of HepG2 cells and a primary culture of rat hepatocytes with PDTC restored insulin responsiveness that was abrogated by IL-6. |
| 870 | 16926159 | These studies are consistent with the ability of PDTC to down-regulate IL-6-induced STAT3 activation by altering the stability of STAT3-Hsp90 complex. |
| 871 | 16997836 | FoxO1 plays an important role in mediating the effect of insulin on hepatic metabolism. |
| 872 | 16997836 | Increased FoxO1 activity is associated with reduced ability of insulin to regulate hepatic glucose production. |
| 873 | 16997836 | We studied the effect of FoxO1 on the ability of insulin to regulate hepatic metabolism in normal vs. insulin-resistant liver under fed and fasting conditions. |
| 874 | 16997836 | Conversely, FoxO1 loss of function, caused by hepatic production of its dominant-negative variant, suppressed hepatic gluconeogenesis, resulting in enhanced glucose disposal and improved insulin sensitivity in db/db mice. |
| 875 | 16997836 | Increased FoxO1 activity resulted in up-regulation of hepatic peroxisome proliferator-activated receptor-gamma coactivator-1beta, fatty acid synthase, and acetyl CoA carboxylase expression, accounting for increased hepatic fat infiltration. |
| 876 | 16997836 | These data indicate that hepatic FoxO1 deregulation impairs the ability of insulin to regulate hepatic metabolism, contributing to the development of hepatic steatosis and abnormal metabolism in diabetes. |
| 877 | 16997836 | FoxO1 plays an important role in mediating the effect of insulin on hepatic metabolism. |
| 878 | 16997836 | Increased FoxO1 activity is associated with reduced ability of insulin to regulate hepatic glucose production. |
| 879 | 16997836 | We studied the effect of FoxO1 on the ability of insulin to regulate hepatic metabolism in normal vs. insulin-resistant liver under fed and fasting conditions. |
| 880 | 16997836 | Conversely, FoxO1 loss of function, caused by hepatic production of its dominant-negative variant, suppressed hepatic gluconeogenesis, resulting in enhanced glucose disposal and improved insulin sensitivity in db/db mice. |
| 881 | 16997836 | Increased FoxO1 activity resulted in up-regulation of hepatic peroxisome proliferator-activated receptor-gamma coactivator-1beta, fatty acid synthase, and acetyl CoA carboxylase expression, accounting for increased hepatic fat infiltration. |
| 882 | 16997836 | These data indicate that hepatic FoxO1 deregulation impairs the ability of insulin to regulate hepatic metabolism, contributing to the development of hepatic steatosis and abnormal metabolism in diabetes. |
| 883 | 16997836 | FoxO1 plays an important role in mediating the effect of insulin on hepatic metabolism. |
| 884 | 16997836 | Increased FoxO1 activity is associated with reduced ability of insulin to regulate hepatic glucose production. |
| 885 | 16997836 | We studied the effect of FoxO1 on the ability of insulin to regulate hepatic metabolism in normal vs. insulin-resistant liver under fed and fasting conditions. |
| 886 | 16997836 | Conversely, FoxO1 loss of function, caused by hepatic production of its dominant-negative variant, suppressed hepatic gluconeogenesis, resulting in enhanced glucose disposal and improved insulin sensitivity in db/db mice. |
| 887 | 16997836 | Increased FoxO1 activity resulted in up-regulation of hepatic peroxisome proliferator-activated receptor-gamma coactivator-1beta, fatty acid synthase, and acetyl CoA carboxylase expression, accounting for increased hepatic fat infiltration. |
| 888 | 16997836 | These data indicate that hepatic FoxO1 deregulation impairs the ability of insulin to regulate hepatic metabolism, contributing to the development of hepatic steatosis and abnormal metabolism in diabetes. |
| 889 | 16997836 | FoxO1 plays an important role in mediating the effect of insulin on hepatic metabolism. |
| 890 | 16997836 | Increased FoxO1 activity is associated with reduced ability of insulin to regulate hepatic glucose production. |
| 891 | 16997836 | We studied the effect of FoxO1 on the ability of insulin to regulate hepatic metabolism in normal vs. insulin-resistant liver under fed and fasting conditions. |
| 892 | 16997836 | Conversely, FoxO1 loss of function, caused by hepatic production of its dominant-negative variant, suppressed hepatic gluconeogenesis, resulting in enhanced glucose disposal and improved insulin sensitivity in db/db mice. |
| 893 | 16997836 | Increased FoxO1 activity resulted in up-regulation of hepatic peroxisome proliferator-activated receptor-gamma coactivator-1beta, fatty acid synthase, and acetyl CoA carboxylase expression, accounting for increased hepatic fat infiltration. |
| 894 | 16997836 | These data indicate that hepatic FoxO1 deregulation impairs the ability of insulin to regulate hepatic metabolism, contributing to the development of hepatic steatosis and abnormal metabolism in diabetes. |
| 895 | 16997836 | FoxO1 plays an important role in mediating the effect of insulin on hepatic metabolism. |
| 896 | 16997836 | Increased FoxO1 activity is associated with reduced ability of insulin to regulate hepatic glucose production. |
| 897 | 16997836 | We studied the effect of FoxO1 on the ability of insulin to regulate hepatic metabolism in normal vs. insulin-resistant liver under fed and fasting conditions. |
| 898 | 16997836 | Conversely, FoxO1 loss of function, caused by hepatic production of its dominant-negative variant, suppressed hepatic gluconeogenesis, resulting in enhanced glucose disposal and improved insulin sensitivity in db/db mice. |
| 899 | 16997836 | Increased FoxO1 activity resulted in up-regulation of hepatic peroxisome proliferator-activated receptor-gamma coactivator-1beta, fatty acid synthase, and acetyl CoA carboxylase expression, accounting for increased hepatic fat infiltration. |
| 900 | 16997836 | These data indicate that hepatic FoxO1 deregulation impairs the ability of insulin to regulate hepatic metabolism, contributing to the development of hepatic steatosis and abnormal metabolism in diabetes. |
| 901 | 16997836 | FoxO1 plays an important role in mediating the effect of insulin on hepatic metabolism. |
| 902 | 16997836 | Increased FoxO1 activity is associated with reduced ability of insulin to regulate hepatic glucose production. |
| 903 | 16997836 | We studied the effect of FoxO1 on the ability of insulin to regulate hepatic metabolism in normal vs. insulin-resistant liver under fed and fasting conditions. |
| 904 | 16997836 | Conversely, FoxO1 loss of function, caused by hepatic production of its dominant-negative variant, suppressed hepatic gluconeogenesis, resulting in enhanced glucose disposal and improved insulin sensitivity in db/db mice. |
| 905 | 16997836 | Increased FoxO1 activity resulted in up-regulation of hepatic peroxisome proliferator-activated receptor-gamma coactivator-1beta, fatty acid synthase, and acetyl CoA carboxylase expression, accounting for increased hepatic fat infiltration. |
| 906 | 16997836 | These data indicate that hepatic FoxO1 deregulation impairs the ability of insulin to regulate hepatic metabolism, contributing to the development of hepatic steatosis and abnormal metabolism in diabetes. |
| 907 | 17024043 | Our results indicate that the transcriptional interaction between FOXO1 and PGC-1alpha is indirect. |
| 908 | 17077083 | Interaction of FoxO1 and TSC2 induces insulin resistance through activation of the mammalian target of rapamycin/p70 S6K pathway. |
| 909 | 17077083 | Both TSC2 (tuberin) and forkhead transcription factor FoxO1 are phosphorylated and inhibited by Akt and play important roles in insulin signaling. |
| 910 | 17077083 | However, little is known about the relationship between TSC2 and FoxO1. |
| 911 | 17077083 | Here we identified TSC2 as a FoxO1-binding protein by using a yeast two-hybrid screening with a murine islet cDNA library. |
| 912 | 17077083 | Among FoxOs, only FoxO1 can be associated with TSC2. |
| 913 | 17077083 | The physical association between the C terminus of TSC2 (amino acids 1280-1499) and FoxO1 degrades the TSC1-TSC2 complex and inhibits GTPase-activating protein activity of TSC2 toward Rheb. |
| 914 | 17077083 | Overexpression of wild type FoxO1 enhances p70 S6K phosphorylation, whereas overexpression of TSC2 can reverse these effects. |
| 915 | 17077083 | Knockdown of endogenous FOXO1 in human vascular endothelial cells decreased phosphorylation of p70 S6K. |
| 916 | 17077083 | Prolonged overexpression of wild type FoxO1 enhanced phosphorylation of serine 307 of IRS1 and decreased phosphorylation of Akt and FoxO1 itself even in the presence of serum. |
| 917 | 17077083 | These data suggest a novel mechanism by which FoxO1 regulates the insulin signaling pathway through negative regulation of TSC2 function. |
| 918 | 17077083 | Interaction of FoxO1 and TSC2 induces insulin resistance through activation of the mammalian target of rapamycin/p70 S6K pathway. |
| 919 | 17077083 | Both TSC2 (tuberin) and forkhead transcription factor FoxO1 are phosphorylated and inhibited by Akt and play important roles in insulin signaling. |
| 920 | 17077083 | However, little is known about the relationship between TSC2 and FoxO1. |
| 921 | 17077083 | Here we identified TSC2 as a FoxO1-binding protein by using a yeast two-hybrid screening with a murine islet cDNA library. |
| 922 | 17077083 | Among FoxOs, only FoxO1 can be associated with TSC2. |
| 923 | 17077083 | The physical association between the C terminus of TSC2 (amino acids 1280-1499) and FoxO1 degrades the TSC1-TSC2 complex and inhibits GTPase-activating protein activity of TSC2 toward Rheb. |
| 924 | 17077083 | Overexpression of wild type FoxO1 enhances p70 S6K phosphorylation, whereas overexpression of TSC2 can reverse these effects. |
| 925 | 17077083 | Knockdown of endogenous FOXO1 in human vascular endothelial cells decreased phosphorylation of p70 S6K. |
| 926 | 17077083 | Prolonged overexpression of wild type FoxO1 enhanced phosphorylation of serine 307 of IRS1 and decreased phosphorylation of Akt and FoxO1 itself even in the presence of serum. |
| 927 | 17077083 | These data suggest a novel mechanism by which FoxO1 regulates the insulin signaling pathway through negative regulation of TSC2 function. |
| 928 | 17077083 | Interaction of FoxO1 and TSC2 induces insulin resistance through activation of the mammalian target of rapamycin/p70 S6K pathway. |
| 929 | 17077083 | Both TSC2 (tuberin) and forkhead transcription factor FoxO1 are phosphorylated and inhibited by Akt and play important roles in insulin signaling. |
| 930 | 17077083 | However, little is known about the relationship between TSC2 and FoxO1. |
| 931 | 17077083 | Here we identified TSC2 as a FoxO1-binding protein by using a yeast two-hybrid screening with a murine islet cDNA library. |
| 932 | 17077083 | Among FoxOs, only FoxO1 can be associated with TSC2. |
| 933 | 17077083 | The physical association between the C terminus of TSC2 (amino acids 1280-1499) and FoxO1 degrades the TSC1-TSC2 complex and inhibits GTPase-activating protein activity of TSC2 toward Rheb. |
| 934 | 17077083 | Overexpression of wild type FoxO1 enhances p70 S6K phosphorylation, whereas overexpression of TSC2 can reverse these effects. |
| 935 | 17077083 | Knockdown of endogenous FOXO1 in human vascular endothelial cells decreased phosphorylation of p70 S6K. |
| 936 | 17077083 | Prolonged overexpression of wild type FoxO1 enhanced phosphorylation of serine 307 of IRS1 and decreased phosphorylation of Akt and FoxO1 itself even in the presence of serum. |
| 937 | 17077083 | These data suggest a novel mechanism by which FoxO1 regulates the insulin signaling pathway through negative regulation of TSC2 function. |
| 938 | 17077083 | Interaction of FoxO1 and TSC2 induces insulin resistance through activation of the mammalian target of rapamycin/p70 S6K pathway. |
| 939 | 17077083 | Both TSC2 (tuberin) and forkhead transcription factor FoxO1 are phosphorylated and inhibited by Akt and play important roles in insulin signaling. |
| 940 | 17077083 | However, little is known about the relationship between TSC2 and FoxO1. |
| 941 | 17077083 | Here we identified TSC2 as a FoxO1-binding protein by using a yeast two-hybrid screening with a murine islet cDNA library. |
| 942 | 17077083 | Among FoxOs, only FoxO1 can be associated with TSC2. |
| 943 | 17077083 | The physical association between the C terminus of TSC2 (amino acids 1280-1499) and FoxO1 degrades the TSC1-TSC2 complex and inhibits GTPase-activating protein activity of TSC2 toward Rheb. |
| 944 | 17077083 | Overexpression of wild type FoxO1 enhances p70 S6K phosphorylation, whereas overexpression of TSC2 can reverse these effects. |
| 945 | 17077083 | Knockdown of endogenous FOXO1 in human vascular endothelial cells decreased phosphorylation of p70 S6K. |
| 946 | 17077083 | Prolonged overexpression of wild type FoxO1 enhanced phosphorylation of serine 307 of IRS1 and decreased phosphorylation of Akt and FoxO1 itself even in the presence of serum. |
| 947 | 17077083 | These data suggest a novel mechanism by which FoxO1 regulates the insulin signaling pathway through negative regulation of TSC2 function. |
| 948 | 17077083 | Interaction of FoxO1 and TSC2 induces insulin resistance through activation of the mammalian target of rapamycin/p70 S6K pathway. |
| 949 | 17077083 | Both TSC2 (tuberin) and forkhead transcription factor FoxO1 are phosphorylated and inhibited by Akt and play important roles in insulin signaling. |
| 950 | 17077083 | However, little is known about the relationship between TSC2 and FoxO1. |
| 951 | 17077083 | Here we identified TSC2 as a FoxO1-binding protein by using a yeast two-hybrid screening with a murine islet cDNA library. |
| 952 | 17077083 | Among FoxOs, only FoxO1 can be associated with TSC2. |
| 953 | 17077083 | The physical association between the C terminus of TSC2 (amino acids 1280-1499) and FoxO1 degrades the TSC1-TSC2 complex and inhibits GTPase-activating protein activity of TSC2 toward Rheb. |
| 954 | 17077083 | Overexpression of wild type FoxO1 enhances p70 S6K phosphorylation, whereas overexpression of TSC2 can reverse these effects. |
| 955 | 17077083 | Knockdown of endogenous FOXO1 in human vascular endothelial cells decreased phosphorylation of p70 S6K. |
| 956 | 17077083 | Prolonged overexpression of wild type FoxO1 enhanced phosphorylation of serine 307 of IRS1 and decreased phosphorylation of Akt and FoxO1 itself even in the presence of serum. |
| 957 | 17077083 | These data suggest a novel mechanism by which FoxO1 regulates the insulin signaling pathway through negative regulation of TSC2 function. |
| 958 | 17077083 | Interaction of FoxO1 and TSC2 induces insulin resistance through activation of the mammalian target of rapamycin/p70 S6K pathway. |
| 959 | 17077083 | Both TSC2 (tuberin) and forkhead transcription factor FoxO1 are phosphorylated and inhibited by Akt and play important roles in insulin signaling. |
| 960 | 17077083 | However, little is known about the relationship between TSC2 and FoxO1. |
| 961 | 17077083 | Here we identified TSC2 as a FoxO1-binding protein by using a yeast two-hybrid screening with a murine islet cDNA library. |
| 962 | 17077083 | Among FoxOs, only FoxO1 can be associated with TSC2. |
| 963 | 17077083 | The physical association between the C terminus of TSC2 (amino acids 1280-1499) and FoxO1 degrades the TSC1-TSC2 complex and inhibits GTPase-activating protein activity of TSC2 toward Rheb. |
| 964 | 17077083 | Overexpression of wild type FoxO1 enhances p70 S6K phosphorylation, whereas overexpression of TSC2 can reverse these effects. |
| 965 | 17077083 | Knockdown of endogenous FOXO1 in human vascular endothelial cells decreased phosphorylation of p70 S6K. |
| 966 | 17077083 | Prolonged overexpression of wild type FoxO1 enhanced phosphorylation of serine 307 of IRS1 and decreased phosphorylation of Akt and FoxO1 itself even in the presence of serum. |
| 967 | 17077083 | These data suggest a novel mechanism by which FoxO1 regulates the insulin signaling pathway through negative regulation of TSC2 function. |
| 968 | 17077083 | Interaction of FoxO1 and TSC2 induces insulin resistance through activation of the mammalian target of rapamycin/p70 S6K pathway. |
| 969 | 17077083 | Both TSC2 (tuberin) and forkhead transcription factor FoxO1 are phosphorylated and inhibited by Akt and play important roles in insulin signaling. |
| 970 | 17077083 | However, little is known about the relationship between TSC2 and FoxO1. |
| 971 | 17077083 | Here we identified TSC2 as a FoxO1-binding protein by using a yeast two-hybrid screening with a murine islet cDNA library. |
| 972 | 17077083 | Among FoxOs, only FoxO1 can be associated with TSC2. |
| 973 | 17077083 | The physical association between the C terminus of TSC2 (amino acids 1280-1499) and FoxO1 degrades the TSC1-TSC2 complex and inhibits GTPase-activating protein activity of TSC2 toward Rheb. |
| 974 | 17077083 | Overexpression of wild type FoxO1 enhances p70 S6K phosphorylation, whereas overexpression of TSC2 can reverse these effects. |
| 975 | 17077083 | Knockdown of endogenous FOXO1 in human vascular endothelial cells decreased phosphorylation of p70 S6K. |
| 976 | 17077083 | Prolonged overexpression of wild type FoxO1 enhanced phosphorylation of serine 307 of IRS1 and decreased phosphorylation of Akt and FoxO1 itself even in the presence of serum. |
| 977 | 17077083 | These data suggest a novel mechanism by which FoxO1 regulates the insulin signaling pathway through negative regulation of TSC2 function. |
| 978 | 17077083 | Interaction of FoxO1 and TSC2 induces insulin resistance through activation of the mammalian target of rapamycin/p70 S6K pathway. |
| 979 | 17077083 | Both TSC2 (tuberin) and forkhead transcription factor FoxO1 are phosphorylated and inhibited by Akt and play important roles in insulin signaling. |
| 980 | 17077083 | However, little is known about the relationship between TSC2 and FoxO1. |
| 981 | 17077083 | Here we identified TSC2 as a FoxO1-binding protein by using a yeast two-hybrid screening with a murine islet cDNA library. |
| 982 | 17077083 | Among FoxOs, only FoxO1 can be associated with TSC2. |
| 983 | 17077083 | The physical association between the C terminus of TSC2 (amino acids 1280-1499) and FoxO1 degrades the TSC1-TSC2 complex and inhibits GTPase-activating protein activity of TSC2 toward Rheb. |
| 984 | 17077083 | Overexpression of wild type FoxO1 enhances p70 S6K phosphorylation, whereas overexpression of TSC2 can reverse these effects. |
| 985 | 17077083 | Knockdown of endogenous FOXO1 in human vascular endothelial cells decreased phosphorylation of p70 S6K. |
| 986 | 17077083 | Prolonged overexpression of wild type FoxO1 enhanced phosphorylation of serine 307 of IRS1 and decreased phosphorylation of Akt and FoxO1 itself even in the presence of serum. |
| 987 | 17077083 | These data suggest a novel mechanism by which FoxO1 regulates the insulin signaling pathway through negative regulation of TSC2 function. |
| 988 | 17077083 | Interaction of FoxO1 and TSC2 induces insulin resistance through activation of the mammalian target of rapamycin/p70 S6K pathway. |
| 989 | 17077083 | Both TSC2 (tuberin) and forkhead transcription factor FoxO1 are phosphorylated and inhibited by Akt and play important roles in insulin signaling. |
| 990 | 17077083 | However, little is known about the relationship between TSC2 and FoxO1. |
| 991 | 17077083 | Here we identified TSC2 as a FoxO1-binding protein by using a yeast two-hybrid screening with a murine islet cDNA library. |
| 992 | 17077083 | Among FoxOs, only FoxO1 can be associated with TSC2. |
| 993 | 17077083 | The physical association between the C terminus of TSC2 (amino acids 1280-1499) and FoxO1 degrades the TSC1-TSC2 complex and inhibits GTPase-activating protein activity of TSC2 toward Rheb. |
| 994 | 17077083 | Overexpression of wild type FoxO1 enhances p70 S6K phosphorylation, whereas overexpression of TSC2 can reverse these effects. |
| 995 | 17077083 | Knockdown of endogenous FOXO1 in human vascular endothelial cells decreased phosphorylation of p70 S6K. |
| 996 | 17077083 | Prolonged overexpression of wild type FoxO1 enhanced phosphorylation of serine 307 of IRS1 and decreased phosphorylation of Akt and FoxO1 itself even in the presence of serum. |
| 997 | 17077083 | These data suggest a novel mechanism by which FoxO1 regulates the insulin signaling pathway through negative regulation of TSC2 function. |
| 998 | 17077083 | Interaction of FoxO1 and TSC2 induces insulin resistance through activation of the mammalian target of rapamycin/p70 S6K pathway. |
| 999 | 17077083 | Both TSC2 (tuberin) and forkhead transcription factor FoxO1 are phosphorylated and inhibited by Akt and play important roles in insulin signaling. |
| 1000 | 17077083 | However, little is known about the relationship between TSC2 and FoxO1. |
| 1001 | 17077083 | Here we identified TSC2 as a FoxO1-binding protein by using a yeast two-hybrid screening with a murine islet cDNA library. |
| 1002 | 17077083 | Among FoxOs, only FoxO1 can be associated with TSC2. |
| 1003 | 17077083 | The physical association between the C terminus of TSC2 (amino acids 1280-1499) and FoxO1 degrades the TSC1-TSC2 complex and inhibits GTPase-activating protein activity of TSC2 toward Rheb. |
| 1004 | 17077083 | Overexpression of wild type FoxO1 enhances p70 S6K phosphorylation, whereas overexpression of TSC2 can reverse these effects. |
| 1005 | 17077083 | Knockdown of endogenous FOXO1 in human vascular endothelial cells decreased phosphorylation of p70 S6K. |
| 1006 | 17077083 | Prolonged overexpression of wild type FoxO1 enhanced phosphorylation of serine 307 of IRS1 and decreased phosphorylation of Akt and FoxO1 itself even in the presence of serum. |
| 1007 | 17077083 | These data suggest a novel mechanism by which FoxO1 regulates the insulin signaling pathway through negative regulation of TSC2 function. |
| 1008 | 17079227 | Estrogen-related receptors stimulate pyruvate dehydrogenase kinase isoform 4 gene expression. |
| 1009 | 17079227 | The pyruvate dehydrogenase complex (PDC) catalyzes the conversion of pyruvate to acetyl-CoA in mitochondria and is a key regulatory enzyme in the oxidation of glucose to acetyl-CoA. |
| 1010 | 17079227 | Phosphorylation of PDC by the pyruvate dehydrogenase kinases (PDK2 and PDK4) inhibits PDC activity. |
| 1011 | 17079227 | In these studies we have investigated the transcriptional regulation of the PDK4 gene by the estrogen-related receptors (ERRalpha and ERRgamma). |
| 1012 | 17079227 | Previously, we found that the peroxisome proliferator-activated receptor gamma coactivator (PGC-1alpha) stimulates the expression of PDK4. |
| 1013 | 17079227 | Here we report that ERRalpha and ERRgamma stimulate the PDK4 gene in hepatoma cells, suggesting a novel role for ERRs in controlling pyruvate metabolism. |
| 1014 | 17079227 | In addition, both ERR isoforms recruit PGC-1alpha to the PDK4 promoter. |
| 1015 | 17079227 | Insulin, which decreases the expression of the PDK4 gene, inhibits the induction of PDK4 by ERRalpha and ERRgamma. |
| 1016 | 17079227 | The forkhead transcription factor (FoxO1) binds the PDK4 gene and contributes to the induction of PDK4 by ERRs and PGC-1alpha. |
| 1017 | 17079227 | Insulin suppresses PDK4 expression in part through the dissociation of FoxO1 and PGC-1alpha from the PDK4 promoter. |
| 1018 | 17079227 | Estrogen-related receptors stimulate pyruvate dehydrogenase kinase isoform 4 gene expression. |
| 1019 | 17079227 | The pyruvate dehydrogenase complex (PDC) catalyzes the conversion of pyruvate to acetyl-CoA in mitochondria and is a key regulatory enzyme in the oxidation of glucose to acetyl-CoA. |
| 1020 | 17079227 | Phosphorylation of PDC by the pyruvate dehydrogenase kinases (PDK2 and PDK4) inhibits PDC activity. |
| 1021 | 17079227 | In these studies we have investigated the transcriptional regulation of the PDK4 gene by the estrogen-related receptors (ERRalpha and ERRgamma). |
| 1022 | 17079227 | Previously, we found that the peroxisome proliferator-activated receptor gamma coactivator (PGC-1alpha) stimulates the expression of PDK4. |
| 1023 | 17079227 | Here we report that ERRalpha and ERRgamma stimulate the PDK4 gene in hepatoma cells, suggesting a novel role for ERRs in controlling pyruvate metabolism. |
| 1024 | 17079227 | In addition, both ERR isoforms recruit PGC-1alpha to the PDK4 promoter. |
| 1025 | 17079227 | Insulin, which decreases the expression of the PDK4 gene, inhibits the induction of PDK4 by ERRalpha and ERRgamma. |
| 1026 | 17079227 | The forkhead transcription factor (FoxO1) binds the PDK4 gene and contributes to the induction of PDK4 by ERRs and PGC-1alpha. |
| 1027 | 17079227 | Insulin suppresses PDK4 expression in part through the dissociation of FoxO1 and PGC-1alpha from the PDK4 promoter. |
| 1028 | 17090532 | SIRT1 regulates adiponectin gene expression through Foxo1-C/enhancer-binding protein alpha transcriptional complex. |
| 1029 | 17090532 | Recent studies have indicated that forkhead transcription factor O1 (Foxo1) and silent information regulator 2 mammalian ortholog SIRT1 are involved in adipogenesis. |
| 1030 | 17090532 | Here we have shown that Foxo1 up-regulates adiponectin gene transcription through a Foxo1-responsive region in the mouse adiponectin promoter that contains two adjacent Foxo1 binding sites. |
| 1031 | 17090532 | Foxo1 interacts with CCAAT/enhancer-binding protein alpha (C/EBPalpha) to form a transcription complex at the mouse adiponectin promoter and up-regulates adiponectin gene transcription. |
| 1032 | 17090532 | Our study has revealed that C/EBPalpha accesses the adiponectin promoter through two Foxo1 binding sites and acts as a co-activator. |
| 1033 | 17090532 | Further, SIRT1 increases adiponectin transcription in adipocytes by activating Foxo1 and enhancing Foxo1 and C/EBPalpha interaction. |
| 1034 | 17090532 | Importantly, both Foxo1 and SIRT1 protein levels were significantly lower in epididymal fat tissues from db/db and high fat diet-induced obese mice compared with normal mice. |
| 1035 | 17090532 | We propose that low expression of SIRT1 and Foxo1 leads to impaired Foxo1-C/EBPalpha complex formation, which contributes to the diminished adiponectin expression in obesity and type 2 diabetes. |
| 1036 | 17090532 | SIRT1 regulates adiponectin gene expression through Foxo1-C/enhancer-binding protein alpha transcriptional complex. |
| 1037 | 17090532 | Recent studies have indicated that forkhead transcription factor O1 (Foxo1) and silent information regulator 2 mammalian ortholog SIRT1 are involved in adipogenesis. |
| 1038 | 17090532 | Here we have shown that Foxo1 up-regulates adiponectin gene transcription through a Foxo1-responsive region in the mouse adiponectin promoter that contains two adjacent Foxo1 binding sites. |
| 1039 | 17090532 | Foxo1 interacts with CCAAT/enhancer-binding protein alpha (C/EBPalpha) to form a transcription complex at the mouse adiponectin promoter and up-regulates adiponectin gene transcription. |
| 1040 | 17090532 | Our study has revealed that C/EBPalpha accesses the adiponectin promoter through two Foxo1 binding sites and acts as a co-activator. |
| 1041 | 17090532 | Further, SIRT1 increases adiponectin transcription in adipocytes by activating Foxo1 and enhancing Foxo1 and C/EBPalpha interaction. |
| 1042 | 17090532 | Importantly, both Foxo1 and SIRT1 protein levels were significantly lower in epididymal fat tissues from db/db and high fat diet-induced obese mice compared with normal mice. |
| 1043 | 17090532 | We propose that low expression of SIRT1 and Foxo1 leads to impaired Foxo1-C/EBPalpha complex formation, which contributes to the diminished adiponectin expression in obesity and type 2 diabetes. |
| 1044 | 17090532 | SIRT1 regulates adiponectin gene expression through Foxo1-C/enhancer-binding protein alpha transcriptional complex. |
| 1045 | 17090532 | Recent studies have indicated that forkhead transcription factor O1 (Foxo1) and silent information regulator 2 mammalian ortholog SIRT1 are involved in adipogenesis. |
| 1046 | 17090532 | Here we have shown that Foxo1 up-regulates adiponectin gene transcription through a Foxo1-responsive region in the mouse adiponectin promoter that contains two adjacent Foxo1 binding sites. |
| 1047 | 17090532 | Foxo1 interacts with CCAAT/enhancer-binding protein alpha (C/EBPalpha) to form a transcription complex at the mouse adiponectin promoter and up-regulates adiponectin gene transcription. |
| 1048 | 17090532 | Our study has revealed that C/EBPalpha accesses the adiponectin promoter through two Foxo1 binding sites and acts as a co-activator. |
| 1049 | 17090532 | Further, SIRT1 increases adiponectin transcription in adipocytes by activating Foxo1 and enhancing Foxo1 and C/EBPalpha interaction. |
| 1050 | 17090532 | Importantly, both Foxo1 and SIRT1 protein levels were significantly lower in epididymal fat tissues from db/db and high fat diet-induced obese mice compared with normal mice. |
| 1051 | 17090532 | We propose that low expression of SIRT1 and Foxo1 leads to impaired Foxo1-C/EBPalpha complex formation, which contributes to the diminished adiponectin expression in obesity and type 2 diabetes. |
| 1052 | 17090532 | SIRT1 regulates adiponectin gene expression through Foxo1-C/enhancer-binding protein alpha transcriptional complex. |
| 1053 | 17090532 | Recent studies have indicated that forkhead transcription factor O1 (Foxo1) and silent information regulator 2 mammalian ortholog SIRT1 are involved in adipogenesis. |
| 1054 | 17090532 | Here we have shown that Foxo1 up-regulates adiponectin gene transcription through a Foxo1-responsive region in the mouse adiponectin promoter that contains two adjacent Foxo1 binding sites. |
| 1055 | 17090532 | Foxo1 interacts with CCAAT/enhancer-binding protein alpha (C/EBPalpha) to form a transcription complex at the mouse adiponectin promoter and up-regulates adiponectin gene transcription. |
| 1056 | 17090532 | Our study has revealed that C/EBPalpha accesses the adiponectin promoter through two Foxo1 binding sites and acts as a co-activator. |
| 1057 | 17090532 | Further, SIRT1 increases adiponectin transcription in adipocytes by activating Foxo1 and enhancing Foxo1 and C/EBPalpha interaction. |
| 1058 | 17090532 | Importantly, both Foxo1 and SIRT1 protein levels were significantly lower in epididymal fat tissues from db/db and high fat diet-induced obese mice compared with normal mice. |
| 1059 | 17090532 | We propose that low expression of SIRT1 and Foxo1 leads to impaired Foxo1-C/EBPalpha complex formation, which contributes to the diminished adiponectin expression in obesity and type 2 diabetes. |
| 1060 | 17090532 | SIRT1 regulates adiponectin gene expression through Foxo1-C/enhancer-binding protein alpha transcriptional complex. |
| 1061 | 17090532 | Recent studies have indicated that forkhead transcription factor O1 (Foxo1) and silent information regulator 2 mammalian ortholog SIRT1 are involved in adipogenesis. |
| 1062 | 17090532 | Here we have shown that Foxo1 up-regulates adiponectin gene transcription through a Foxo1-responsive region in the mouse adiponectin promoter that contains two adjacent Foxo1 binding sites. |
| 1063 | 17090532 | Foxo1 interacts with CCAAT/enhancer-binding protein alpha (C/EBPalpha) to form a transcription complex at the mouse adiponectin promoter and up-regulates adiponectin gene transcription. |
| 1064 | 17090532 | Our study has revealed that C/EBPalpha accesses the adiponectin promoter through two Foxo1 binding sites and acts as a co-activator. |
| 1065 | 17090532 | Further, SIRT1 increases adiponectin transcription in adipocytes by activating Foxo1 and enhancing Foxo1 and C/EBPalpha interaction. |
| 1066 | 17090532 | Importantly, both Foxo1 and SIRT1 protein levels were significantly lower in epididymal fat tissues from db/db and high fat diet-induced obese mice compared with normal mice. |
| 1067 | 17090532 | We propose that low expression of SIRT1 and Foxo1 leads to impaired Foxo1-C/EBPalpha complex formation, which contributes to the diminished adiponectin expression in obesity and type 2 diabetes. |
| 1068 | 17090532 | SIRT1 regulates adiponectin gene expression through Foxo1-C/enhancer-binding protein alpha transcriptional complex. |
| 1069 | 17090532 | Recent studies have indicated that forkhead transcription factor O1 (Foxo1) and silent information regulator 2 mammalian ortholog SIRT1 are involved in adipogenesis. |
| 1070 | 17090532 | Here we have shown that Foxo1 up-regulates adiponectin gene transcription through a Foxo1-responsive region in the mouse adiponectin promoter that contains two adjacent Foxo1 binding sites. |
| 1071 | 17090532 | Foxo1 interacts with CCAAT/enhancer-binding protein alpha (C/EBPalpha) to form a transcription complex at the mouse adiponectin promoter and up-regulates adiponectin gene transcription. |
| 1072 | 17090532 | Our study has revealed that C/EBPalpha accesses the adiponectin promoter through two Foxo1 binding sites and acts as a co-activator. |
| 1073 | 17090532 | Further, SIRT1 increases adiponectin transcription in adipocytes by activating Foxo1 and enhancing Foxo1 and C/EBPalpha interaction. |
| 1074 | 17090532 | Importantly, both Foxo1 and SIRT1 protein levels were significantly lower in epididymal fat tissues from db/db and high fat diet-induced obese mice compared with normal mice. |
| 1075 | 17090532 | We propose that low expression of SIRT1 and Foxo1 leads to impaired Foxo1-C/EBPalpha complex formation, which contributes to the diminished adiponectin expression in obesity and type 2 diabetes. |
| 1076 | 17090532 | SIRT1 regulates adiponectin gene expression through Foxo1-C/enhancer-binding protein alpha transcriptional complex. |
| 1077 | 17090532 | Recent studies have indicated that forkhead transcription factor O1 (Foxo1) and silent information regulator 2 mammalian ortholog SIRT1 are involved in adipogenesis. |
| 1078 | 17090532 | Here we have shown that Foxo1 up-regulates adiponectin gene transcription through a Foxo1-responsive region in the mouse adiponectin promoter that contains two adjacent Foxo1 binding sites. |
| 1079 | 17090532 | Foxo1 interacts with CCAAT/enhancer-binding protein alpha (C/EBPalpha) to form a transcription complex at the mouse adiponectin promoter and up-regulates adiponectin gene transcription. |
| 1080 | 17090532 | Our study has revealed that C/EBPalpha accesses the adiponectin promoter through two Foxo1 binding sites and acts as a co-activator. |
| 1081 | 17090532 | Further, SIRT1 increases adiponectin transcription in adipocytes by activating Foxo1 and enhancing Foxo1 and C/EBPalpha interaction. |
| 1082 | 17090532 | Importantly, both Foxo1 and SIRT1 protein levels were significantly lower in epididymal fat tissues from db/db and high fat diet-induced obese mice compared with normal mice. |
| 1083 | 17090532 | We propose that low expression of SIRT1 and Foxo1 leads to impaired Foxo1-C/EBPalpha complex formation, which contributes to the diminished adiponectin expression in obesity and type 2 diabetes. |
| 1084 | 17107961 | The transcription factor Foxo1 protects beta-cells against oxidative stress induced by hyperglycemia and prevents beta-cell replication in insulin-resistant states. |
| 1085 | 17107961 | Functional analyses show decreased glucose utilization and insulin secretion in beta-cells overexpressing Foxo1. |
| 1086 | 17107961 | The transcription factor Foxo1 protects beta-cells against oxidative stress induced by hyperglycemia and prevents beta-cell replication in insulin-resistant states. |
| 1087 | 17107961 | Functional analyses show decreased glucose utilization and insulin secretion in beta-cells overexpressing Foxo1. |
| 1088 | 17130472 | We found insulin receptor substrate (IRS)2 and enhanced-activated Akt immunoreactivity in islets and ducts that correlated with increased pancreatic duodenal homeobox (PDX)1 expression. |
| 1089 | 17130472 | In contrast, forkhead box O1 expression was decreased in islets but increased in ducts, suggesting distinct PDX1 regulatory mechanisms in these tissues. |
| 1090 | 17210752 | Bidirectional regulation of upstream IGF-I/insulin receptor signaling and downstream FOXO1 in cardiomyocytes. |
| 1091 | 17210752 | 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. |
| 1092 | 17210752 | This study was carried out to elucidate how IGF-I and insulin receptor signaling modulate FOXO1 in cardiomyocytes. |
| 1093 | 17210752 | In cardiomyocytes, activation of IGF-I receptor and insulin receptor lead to rapid phosphorylation of FOXO1. |
| 1094 | 17210752 | Inhibition of phosphatidylinositol 3-kinase/Akt pathway suppressed the effect of insulin and IGF-I on FOXO1 phosphorylation. |
| 1095 | 17210752 | To explore whether FOXO1 could modulate IGF-I and insulin signaling, a constitutively active FOXO1 was overexpressed in cardiomyocytes. |
| 1096 | 17210752 | The abundance of insulin receptor and IGF-I receptor was significantly upregulated in the cells overexpressing active FOXO1, accompanied by increased receptor phosphorylation upon insulin/IGF-I stimulation. |
| 1097 | 17210752 | Interestingly, overexpression of constitutively active FOXO1 also led to activation of MEK and Akt phosphorylation. |
| 1098 | 17210752 | IGF-I-stimulated MEK and Akt phosphorylation were augmented byoverexpression of constitutively active FOXO1. |
| 1099 | 17210752 | These findings indicate bidirectional regulation of insulin/IGF-I receptor signaling and FOXO1 in cardiomyocytes. |
| 1100 | 17210752 | FOXO1 may provide feedback control through upregulation of insulin and IGF-I receptor signaling. |
| 1101 | 17210752 | Bidirectional regulation of upstream IGF-I/insulin receptor signaling and downstream FOXO1 in cardiomyocytes. |
| 1102 | 17210752 | 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. |
| 1103 | 17210752 | This study was carried out to elucidate how IGF-I and insulin receptor signaling modulate FOXO1 in cardiomyocytes. |
| 1104 | 17210752 | In cardiomyocytes, activation of IGF-I receptor and insulin receptor lead to rapid phosphorylation of FOXO1. |
| 1105 | 17210752 | Inhibition of phosphatidylinositol 3-kinase/Akt pathway suppressed the effect of insulin and IGF-I on FOXO1 phosphorylation. |
| 1106 | 17210752 | To explore whether FOXO1 could modulate IGF-I and insulin signaling, a constitutively active FOXO1 was overexpressed in cardiomyocytes. |
| 1107 | 17210752 | The abundance of insulin receptor and IGF-I receptor was significantly upregulated in the cells overexpressing active FOXO1, accompanied by increased receptor phosphorylation upon insulin/IGF-I stimulation. |
| 1108 | 17210752 | Interestingly, overexpression of constitutively active FOXO1 also led to activation of MEK and Akt phosphorylation. |
| 1109 | 17210752 | IGF-I-stimulated MEK and Akt phosphorylation were augmented byoverexpression of constitutively active FOXO1. |
| 1110 | 17210752 | These findings indicate bidirectional regulation of insulin/IGF-I receptor signaling and FOXO1 in cardiomyocytes. |
| 1111 | 17210752 | FOXO1 may provide feedback control through upregulation of insulin and IGF-I receptor signaling. |
| 1112 | 17210752 | Bidirectional regulation of upstream IGF-I/insulin receptor signaling and downstream FOXO1 in cardiomyocytes. |
| 1113 | 17210752 | 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. |
| 1114 | 17210752 | This study was carried out to elucidate how IGF-I and insulin receptor signaling modulate FOXO1 in cardiomyocytes. |
| 1115 | 17210752 | In cardiomyocytes, activation of IGF-I receptor and insulin receptor lead to rapid phosphorylation of FOXO1. |
| 1116 | 17210752 | Inhibition of phosphatidylinositol 3-kinase/Akt pathway suppressed the effect of insulin and IGF-I on FOXO1 phosphorylation. |
| 1117 | 17210752 | To explore whether FOXO1 could modulate IGF-I and insulin signaling, a constitutively active FOXO1 was overexpressed in cardiomyocytes. |
| 1118 | 17210752 | The abundance of insulin receptor and IGF-I receptor was significantly upregulated in the cells overexpressing active FOXO1, accompanied by increased receptor phosphorylation upon insulin/IGF-I stimulation. |
| 1119 | 17210752 | Interestingly, overexpression of constitutively active FOXO1 also led to activation of MEK and Akt phosphorylation. |
| 1120 | 17210752 | IGF-I-stimulated MEK and Akt phosphorylation were augmented byoverexpression of constitutively active FOXO1. |
| 1121 | 17210752 | These findings indicate bidirectional regulation of insulin/IGF-I receptor signaling and FOXO1 in cardiomyocytes. |
| 1122 | 17210752 | FOXO1 may provide feedback control through upregulation of insulin and IGF-I receptor signaling. |
| 1123 | 17210752 | Bidirectional regulation of upstream IGF-I/insulin receptor signaling and downstream FOXO1 in cardiomyocytes. |
| 1124 | 17210752 | 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. |
| 1125 | 17210752 | This study was carried out to elucidate how IGF-I and insulin receptor signaling modulate FOXO1 in cardiomyocytes. |
| 1126 | 17210752 | In cardiomyocytes, activation of IGF-I receptor and insulin receptor lead to rapid phosphorylation of FOXO1. |
| 1127 | 17210752 | Inhibition of phosphatidylinositol 3-kinase/Akt pathway suppressed the effect of insulin and IGF-I on FOXO1 phosphorylation. |
| 1128 | 17210752 | To explore whether FOXO1 could modulate IGF-I and insulin signaling, a constitutively active FOXO1 was overexpressed in cardiomyocytes. |
| 1129 | 17210752 | The abundance of insulin receptor and IGF-I receptor was significantly upregulated in the cells overexpressing active FOXO1, accompanied by increased receptor phosphorylation upon insulin/IGF-I stimulation. |
| 1130 | 17210752 | Interestingly, overexpression of constitutively active FOXO1 also led to activation of MEK and Akt phosphorylation. |
| 1131 | 17210752 | IGF-I-stimulated MEK and Akt phosphorylation were augmented byoverexpression of constitutively active FOXO1. |
| 1132 | 17210752 | These findings indicate bidirectional regulation of insulin/IGF-I receptor signaling and FOXO1 in cardiomyocytes. |
| 1133 | 17210752 | FOXO1 may provide feedback control through upregulation of insulin and IGF-I receptor signaling. |
| 1134 | 17210752 | Bidirectional regulation of upstream IGF-I/insulin receptor signaling and downstream FOXO1 in cardiomyocytes. |
| 1135 | 17210752 | 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. |
| 1136 | 17210752 | This study was carried out to elucidate how IGF-I and insulin receptor signaling modulate FOXO1 in cardiomyocytes. |
| 1137 | 17210752 | In cardiomyocytes, activation of IGF-I receptor and insulin receptor lead to rapid phosphorylation of FOXO1. |
| 1138 | 17210752 | Inhibition of phosphatidylinositol 3-kinase/Akt pathway suppressed the effect of insulin and IGF-I on FOXO1 phosphorylation. |
| 1139 | 17210752 | To explore whether FOXO1 could modulate IGF-I and insulin signaling, a constitutively active FOXO1 was overexpressed in cardiomyocytes. |
| 1140 | 17210752 | The abundance of insulin receptor and IGF-I receptor was significantly upregulated in the cells overexpressing active FOXO1, accompanied by increased receptor phosphorylation upon insulin/IGF-I stimulation. |
| 1141 | 17210752 | Interestingly, overexpression of constitutively active FOXO1 also led to activation of MEK and Akt phosphorylation. |
| 1142 | 17210752 | IGF-I-stimulated MEK and Akt phosphorylation were augmented byoverexpression of constitutively active FOXO1. |
| 1143 | 17210752 | These findings indicate bidirectional regulation of insulin/IGF-I receptor signaling and FOXO1 in cardiomyocytes. |
| 1144 | 17210752 | FOXO1 may provide feedback control through upregulation of insulin and IGF-I receptor signaling. |
| 1145 | 17210752 | Bidirectional regulation of upstream IGF-I/insulin receptor signaling and downstream FOXO1 in cardiomyocytes. |
| 1146 | 17210752 | 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. |
| 1147 | 17210752 | This study was carried out to elucidate how IGF-I and insulin receptor signaling modulate FOXO1 in cardiomyocytes. |
| 1148 | 17210752 | In cardiomyocytes, activation of IGF-I receptor and insulin receptor lead to rapid phosphorylation of FOXO1. |
| 1149 | 17210752 | Inhibition of phosphatidylinositol 3-kinase/Akt pathway suppressed the effect of insulin and IGF-I on FOXO1 phosphorylation. |
| 1150 | 17210752 | To explore whether FOXO1 could modulate IGF-I and insulin signaling, a constitutively active FOXO1 was overexpressed in cardiomyocytes. |
| 1151 | 17210752 | The abundance of insulin receptor and IGF-I receptor was significantly upregulated in the cells overexpressing active FOXO1, accompanied by increased receptor phosphorylation upon insulin/IGF-I stimulation. |
| 1152 | 17210752 | Interestingly, overexpression of constitutively active FOXO1 also led to activation of MEK and Akt phosphorylation. |
| 1153 | 17210752 | IGF-I-stimulated MEK and Akt phosphorylation were augmented byoverexpression of constitutively active FOXO1. |
| 1154 | 17210752 | These findings indicate bidirectional regulation of insulin/IGF-I receptor signaling and FOXO1 in cardiomyocytes. |
| 1155 | 17210752 | FOXO1 may provide feedback control through upregulation of insulin and IGF-I receptor signaling. |
| 1156 | 17210752 | Bidirectional regulation of upstream IGF-I/insulin receptor signaling and downstream FOXO1 in cardiomyocytes. |
| 1157 | 17210752 | 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. |
| 1158 | 17210752 | This study was carried out to elucidate how IGF-I and insulin receptor signaling modulate FOXO1 in cardiomyocytes. |
| 1159 | 17210752 | In cardiomyocytes, activation of IGF-I receptor and insulin receptor lead to rapid phosphorylation of FOXO1. |
| 1160 | 17210752 | Inhibition of phosphatidylinositol 3-kinase/Akt pathway suppressed the effect of insulin and IGF-I on FOXO1 phosphorylation. |
| 1161 | 17210752 | To explore whether FOXO1 could modulate IGF-I and insulin signaling, a constitutively active FOXO1 was overexpressed in cardiomyocytes. |
| 1162 | 17210752 | The abundance of insulin receptor and IGF-I receptor was significantly upregulated in the cells overexpressing active FOXO1, accompanied by increased receptor phosphorylation upon insulin/IGF-I stimulation. |
| 1163 | 17210752 | Interestingly, overexpression of constitutively active FOXO1 also led to activation of MEK and Akt phosphorylation. |
| 1164 | 17210752 | IGF-I-stimulated MEK and Akt phosphorylation were augmented byoverexpression of constitutively active FOXO1. |
| 1165 | 17210752 | These findings indicate bidirectional regulation of insulin/IGF-I receptor signaling and FOXO1 in cardiomyocytes. |
| 1166 | 17210752 | FOXO1 may provide feedback control through upregulation of insulin and IGF-I receptor signaling. |
| 1167 | 17210752 | Bidirectional regulation of upstream IGF-I/insulin receptor signaling and downstream FOXO1 in cardiomyocytes. |
| 1168 | 17210752 | 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. |
| 1169 | 17210752 | This study was carried out to elucidate how IGF-I and insulin receptor signaling modulate FOXO1 in cardiomyocytes. |
| 1170 | 17210752 | In cardiomyocytes, activation of IGF-I receptor and insulin receptor lead to rapid phosphorylation of FOXO1. |
| 1171 | 17210752 | Inhibition of phosphatidylinositol 3-kinase/Akt pathway suppressed the effect of insulin and IGF-I on FOXO1 phosphorylation. |
| 1172 | 17210752 | To explore whether FOXO1 could modulate IGF-I and insulin signaling, a constitutively active FOXO1 was overexpressed in cardiomyocytes. |
| 1173 | 17210752 | The abundance of insulin receptor and IGF-I receptor was significantly upregulated in the cells overexpressing active FOXO1, accompanied by increased receptor phosphorylation upon insulin/IGF-I stimulation. |
| 1174 | 17210752 | Interestingly, overexpression of constitutively active FOXO1 also led to activation of MEK and Akt phosphorylation. |
| 1175 | 17210752 | IGF-I-stimulated MEK and Akt phosphorylation were augmented byoverexpression of constitutively active FOXO1. |
| 1176 | 17210752 | These findings indicate bidirectional regulation of insulin/IGF-I receptor signaling and FOXO1 in cardiomyocytes. |
| 1177 | 17210752 | FOXO1 may provide feedback control through upregulation of insulin and IGF-I receptor signaling. |
| 1178 | 17210752 | Bidirectional regulation of upstream IGF-I/insulin receptor signaling and downstream FOXO1 in cardiomyocytes. |
| 1179 | 17210752 | 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. |
| 1180 | 17210752 | This study was carried out to elucidate how IGF-I and insulin receptor signaling modulate FOXO1 in cardiomyocytes. |
| 1181 | 17210752 | In cardiomyocytes, activation of IGF-I receptor and insulin receptor lead to rapid phosphorylation of FOXO1. |
| 1182 | 17210752 | Inhibition of phosphatidylinositol 3-kinase/Akt pathway suppressed the effect of insulin and IGF-I on FOXO1 phosphorylation. |
| 1183 | 17210752 | To explore whether FOXO1 could modulate IGF-I and insulin signaling, a constitutively active FOXO1 was overexpressed in cardiomyocytes. |
| 1184 | 17210752 | The abundance of insulin receptor and IGF-I receptor was significantly upregulated in the cells overexpressing active FOXO1, accompanied by increased receptor phosphorylation upon insulin/IGF-I stimulation. |
| 1185 | 17210752 | Interestingly, overexpression of constitutively active FOXO1 also led to activation of MEK and Akt phosphorylation. |
| 1186 | 17210752 | IGF-I-stimulated MEK and Akt phosphorylation were augmented byoverexpression of constitutively active FOXO1. |
| 1187 | 17210752 | These findings indicate bidirectional regulation of insulin/IGF-I receptor signaling and FOXO1 in cardiomyocytes. |
| 1188 | 17210752 | FOXO1 may provide feedback control through upregulation of insulin and IGF-I receptor signaling. |
| 1189 | 17210752 | Bidirectional regulation of upstream IGF-I/insulin receptor signaling and downstream FOXO1 in cardiomyocytes. |
| 1190 | 17210752 | 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. |
| 1191 | 17210752 | This study was carried out to elucidate how IGF-I and insulin receptor signaling modulate FOXO1 in cardiomyocytes. |
| 1192 | 17210752 | In cardiomyocytes, activation of IGF-I receptor and insulin receptor lead to rapid phosphorylation of FOXO1. |
| 1193 | 17210752 | Inhibition of phosphatidylinositol 3-kinase/Akt pathway suppressed the effect of insulin and IGF-I on FOXO1 phosphorylation. |
| 1194 | 17210752 | To explore whether FOXO1 could modulate IGF-I and insulin signaling, a constitutively active FOXO1 was overexpressed in cardiomyocytes. |
| 1195 | 17210752 | The abundance of insulin receptor and IGF-I receptor was significantly upregulated in the cells overexpressing active FOXO1, accompanied by increased receptor phosphorylation upon insulin/IGF-I stimulation. |
| 1196 | 17210752 | Interestingly, overexpression of constitutively active FOXO1 also led to activation of MEK and Akt phosphorylation. |
| 1197 | 17210752 | IGF-I-stimulated MEK and Akt phosphorylation were augmented byoverexpression of constitutively active FOXO1. |
| 1198 | 17210752 | These findings indicate bidirectional regulation of insulin/IGF-I receptor signaling and FOXO1 in cardiomyocytes. |
| 1199 | 17210752 | FOXO1 may provide feedback control through upregulation of insulin and IGF-I receptor signaling. |
| 1200 | 17210752 | Bidirectional regulation of upstream IGF-I/insulin receptor signaling and downstream FOXO1 in cardiomyocytes. |
| 1201 | 17210752 | 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. |
| 1202 | 17210752 | This study was carried out to elucidate how IGF-I and insulin receptor signaling modulate FOXO1 in cardiomyocytes. |
| 1203 | 17210752 | In cardiomyocytes, activation of IGF-I receptor and insulin receptor lead to rapid phosphorylation of FOXO1. |
| 1204 | 17210752 | Inhibition of phosphatidylinositol 3-kinase/Akt pathway suppressed the effect of insulin and IGF-I on FOXO1 phosphorylation. |
| 1205 | 17210752 | To explore whether FOXO1 could modulate IGF-I and insulin signaling, a constitutively active FOXO1 was overexpressed in cardiomyocytes. |
| 1206 | 17210752 | The abundance of insulin receptor and IGF-I receptor was significantly upregulated in the cells overexpressing active FOXO1, accompanied by increased receptor phosphorylation upon insulin/IGF-I stimulation. |
| 1207 | 17210752 | Interestingly, overexpression of constitutively active FOXO1 also led to activation of MEK and Akt phosphorylation. |
| 1208 | 17210752 | IGF-I-stimulated MEK and Akt phosphorylation were augmented byoverexpression of constitutively active FOXO1. |
| 1209 | 17210752 | These findings indicate bidirectional regulation of insulin/IGF-I receptor signaling and FOXO1 in cardiomyocytes. |
| 1210 | 17210752 | FOXO1 may provide feedback control through upregulation of insulin and IGF-I receptor signaling. |
| 1211 | 17245409 | Haplotypes in the human Foxo1a and Foxo3a genes; impact on disease and mortality at old age. |
| 1212 | 17245409 | In mammals, the Daf-16 homologues are forkhead (FOXO) transcription factors, of which specific functions have been identified for Foxo1a and Foxo3a. |
| 1213 | 17245409 | Here, we analysed the effect of genetic variance in Foxo1a and Foxo3a on metabolic profile, age-related diseases, fertility, fecundity and mortality. |
| 1214 | 17245409 | In conclusion, this study shows that genetic variation in evolutionarily conserved Foxo1a and Foxo3a genes influences lifespan in our study population. |
| 1215 | 17245409 | Haplotypes in the human Foxo1a and Foxo3a genes; impact on disease and mortality at old age. |
| 1216 | 17245409 | In mammals, the Daf-16 homologues are forkhead (FOXO) transcription factors, of which specific functions have been identified for Foxo1a and Foxo3a. |
| 1217 | 17245409 | Here, we analysed the effect of genetic variance in Foxo1a and Foxo3a on metabolic profile, age-related diseases, fertility, fecundity and mortality. |
| 1218 | 17245409 | In conclusion, this study shows that genetic variation in evolutionarily conserved Foxo1a and Foxo3a genes influences lifespan in our study population. |
| 1219 | 17245409 | Haplotypes in the human Foxo1a and Foxo3a genes; impact on disease and mortality at old age. |
| 1220 | 17245409 | In mammals, the Daf-16 homologues are forkhead (FOXO) transcription factors, of which specific functions have been identified for Foxo1a and Foxo3a. |
| 1221 | 17245409 | Here, we analysed the effect of genetic variance in Foxo1a and Foxo3a on metabolic profile, age-related diseases, fertility, fecundity and mortality. |
| 1222 | 17245409 | In conclusion, this study shows that genetic variation in evolutionarily conserved Foxo1a and Foxo3a genes influences lifespan in our study population. |
| 1223 | 17245409 | Haplotypes in the human Foxo1a and Foxo3a genes; impact on disease and mortality at old age. |
| 1224 | 17245409 | In mammals, the Daf-16 homologues are forkhead (FOXO) transcription factors, of which specific functions have been identified for Foxo1a and Foxo3a. |
| 1225 | 17245409 | Here, we analysed the effect of genetic variance in Foxo1a and Foxo3a on metabolic profile, age-related diseases, fertility, fecundity and mortality. |
| 1226 | 17245409 | In conclusion, this study shows that genetic variation in evolutionarily conserved Foxo1a and Foxo3a genes influences lifespan in our study population. |
| 1227 | 17270172 | Our results suggest that quiescence of small cells correlates with up-regulation of Cdk inhibitors p27(Kip1), p16(INK4a) and p21(CIP1), PTEN, Hep27 and Foxo1a and with down-regulation of c-Myc and the receptors for EGF, FGF2 and HGF. |
| 1228 | 17270172 | The exit from quiescence correlates with activation of EGFR expression and down-regulation of p27(Kip1) and p16(INK4a). |
| 1229 | 17279346 | SREBP-1c and TFE3, energy transcription factors that regulate hepatic insulin signaling. |
| 1230 | 17279346 | Conversely, TFE3 is a novel bHLH transcription factor that strongly activates various insulin signaling molecules, protecting against the development of insulin resistance and the metabolic syndrome. |
| 1231 | 17279346 | Regulation of IRS-2 is the primary site where TFE3 in synergy with Foxo1, and SREBP-1c converge. |
| 1232 | 17279346 | Taken together, TFE3/Foxo1 and SREBP-1c reciprocally regulate IRS-2 expression and insulin sensitivity in the liver. |
| 1233 | 17279346 | In this review, I will discuss roles of SREBP-1c and TFE3 in homeostasis of energy metabolism and in metabolic disturbances, focusing on hepatic insulin sensitivity. |
| 1234 | 17317207 | Transcriptional regulation of the GLUT4 gene: from PPAR-gamma and FOXO1 to FFA and inflammation. |
| 1235 | 17317207 | The insulin-responsive glucose transporter 4 (GLUT4) has a major role in glucose uptake and metabolism in insulin target tissues (i.e. adipose and muscle cells). |
| 1236 | 17317207 | In these tissues, the peroxisome proliferator-activated receptor (PPAR) family of nuclear receptors and the winged-helix-forkhead box class O (FOXO) family of factors are two key families of transcription factors that regulate glucose homeostasis and insulin responsiveness. |
| 1237 | 17317207 | Based on our studies of the interplay between PPAR-gamma, FOXO1 and free fatty acids, and inflammation in regulating GLUT4 transcription in sickness and in health, we suggest a novel paradigm to increase insulin sensitivity in bona fide insulin target cells. |
| 1238 | 17317207 | Transcriptional regulation of the GLUT4 gene: from PPAR-gamma and FOXO1 to FFA and inflammation. |
| 1239 | 17317207 | The insulin-responsive glucose transporter 4 (GLUT4) has a major role in glucose uptake and metabolism in insulin target tissues (i.e. adipose and muscle cells). |
| 1240 | 17317207 | In these tissues, the peroxisome proliferator-activated receptor (PPAR) family of nuclear receptors and the winged-helix-forkhead box class O (FOXO) family of factors are two key families of transcription factors that regulate glucose homeostasis and insulin responsiveness. |
| 1241 | 17317207 | Based on our studies of the interplay between PPAR-gamma, FOXO1 and free fatty acids, and inflammation in regulating GLUT4 transcription in sickness and in health, we suggest a novel paradigm to increase insulin sensitivity in bona fide insulin target cells. |
| 1242 | 17374693 | The FoxO1 downregulation correlated with an increase in the production of ROS and a proinflammatory adipokine pattern characterized by a decrease in adiponectin and an increase in IL-6, plasminogen activator inhibitor-1, and monocyte chemotactic protein-1 mRNA expression levels. |
| 1243 | 17374693 | Together these results indicate that the insulin-resistant adipocyte produced by the exposure to a high concentration of fatty acids is characterized by decreased levels of FoxO1. |
| 1244 | 17374693 | These data also suggest that modulation of the Sirt1/FoxO1 pathway is a potentially useful therapeutic target for the obesity-induced dysfunctional adipocyte. |
| 1245 | 17374693 | The FoxO1 downregulation correlated with an increase in the production of ROS and a proinflammatory adipokine pattern characterized by a decrease in adiponectin and an increase in IL-6, plasminogen activator inhibitor-1, and monocyte chemotactic protein-1 mRNA expression levels. |
| 1246 | 17374693 | Together these results indicate that the insulin-resistant adipocyte produced by the exposure to a high concentration of fatty acids is characterized by decreased levels of FoxO1. |
| 1247 | 17374693 | These data also suggest that modulation of the Sirt1/FoxO1 pathway is a potentially useful therapeutic target for the obesity-induced dysfunctional adipocyte. |
| 1248 | 17374693 | The FoxO1 downregulation correlated with an increase in the production of ROS and a proinflammatory adipokine pattern characterized by a decrease in adiponectin and an increase in IL-6, plasminogen activator inhibitor-1, and monocyte chemotactic protein-1 mRNA expression levels. |
| 1249 | 17374693 | Together these results indicate that the insulin-resistant adipocyte produced by the exposure to a high concentration of fatty acids is characterized by decreased levels of FoxO1. |
| 1250 | 17374693 | These data also suggest that modulation of the Sirt1/FoxO1 pathway is a potentially useful therapeutic target for the obesity-induced dysfunctional adipocyte. |
| 1251 | 17510498 | The expression pattern of FoxO1 during pancreatic organogenesis is similar to that of Pdx1, Nkx2.2 and Pax4, transcription factors known to be critical for beta cell development. |
| 1252 | 17510498 | FoxO1 is expressed in a subset of pancreatic duct cells, in which insulin and/or Pdx1 are occasionally expressed. |
| 1253 | 17510498 | FoxO1 inhibits beta cell proliferation through suppression of Pdx1 by competing with FoxA2 and protects against beta cell failure induced by oxidative stress through NeuroD and MafA induction. |
| 1254 | 17510498 | The expression pattern of FoxO1 during pancreatic organogenesis is similar to that of Pdx1, Nkx2.2 and Pax4, transcription factors known to be critical for beta cell development. |
| 1255 | 17510498 | FoxO1 is expressed in a subset of pancreatic duct cells, in which insulin and/or Pdx1 are occasionally expressed. |
| 1256 | 17510498 | FoxO1 inhibits beta cell proliferation through suppression of Pdx1 by competing with FoxA2 and protects against beta cell failure induced by oxidative stress through NeuroD and MafA induction. |
| 1257 | 17510498 | The expression pattern of FoxO1 during pancreatic organogenesis is similar to that of Pdx1, Nkx2.2 and Pax4, transcription factors known to be critical for beta cell development. |
| 1258 | 17510498 | FoxO1 is expressed in a subset of pancreatic duct cells, in which insulin and/or Pdx1 are occasionally expressed. |
| 1259 | 17510498 | FoxO1 inhibits beta cell proliferation through suppression of Pdx1 by competing with FoxA2 and protects against beta cell failure induced by oxidative stress through NeuroD and MafA induction. |
| 1260 | 17575086 | Western blot analysis revealed enhanced phosphorylation of nuclear factor Foxo3a without changes in Foxo3a, Foxo1a, pFoxo1a, silent information regulator (Sirt), and Akt and pAkt in hearts of high-fat diet-fed FVB mice. |
| 1261 | 17575086 | The peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha), a key regulator of mitochondrial biogenesis, was significantly depressed by high-fat diet feeding and in vitro palmitic acid treatment. |
| 1262 | 17575086 | RT-PCR further depicted reduced levels of the PGC-1alpha downstream nuclear respiratory factors 1 and 2, mitochondrial transcription factor A, and mitochondrial DNA copy number in hearts of high-fat-fed FVB mice. |
| 1263 | 17647137 | Recently, two types of adiponectin receptors (AdipoR1 and AdipoR2) were identified. |
| 1264 | 17647137 | While, although physical exercise is useful for improving insulin sensitivity, the effect of physical exercise on adiponectin and adiponectin receptors are still unclear. |
| 1265 | 17647137 | Following an acute exercise, plasma glucose, insulin, FFA, and adiponectin were measured. |
| 1266 | 17647137 | Although acute exercise did not significantly change plasma adiponectin concentration at 2 hours or 18 hours after the exercise compared with control group, the expression levels of AdipoR1 significantly increased in both skeletal muscle (2H: 1.2-fold, p=0.0423, 18H: 1.4-fold, p=0.0006) and liver (2H: 1.3-fold, p=0.0448) compared with control group. |
| 1267 | 17647137 | These findings suggest that acute exercise affects the expression level of adiponectin receptors, and an increase of Foxo1 expression might be relative to regulate adiponectin receptors. |
| 1268 | 17681146 | SIRT2 regulates adipocyte differentiation through FoxO1 acetylation/deacetylation. |
| 1269 | 17681146 | Both effects are accompanied by corresponding changes in the expression of PPARgamma, C/EBPalpha, and genes marking terminal adipocyte differentiation, including Glut4, aP2, and fatty acid synthase. |
| 1270 | 17681146 | The mechanism underlying the effects of reduced SIRT2 in 3T3-L1 adipocytes includes increased acetylation of FOXO1, with direct interaction between SIRT2 and FOXO1. |
| 1271 | 17681146 | Thus, Sirt2 acts as an important regulator of adipocyte differentiation through modulation of FOXO1 acetylation/phosphorylation and activity and may play a role in controlling adipose tissue mass and function. |
| 1272 | 17767907 | Conversely, Foxo1 deletion in liver curtails excessive glucose production caused by generalized ablation of insulin receptors and prevents neonatal diabetes and hepatosteatosis in insulin receptor knockout mice. |
| 1273 | 17805301 | Insulin modulates gluconeogenesis by inhibition of the coactivator TORC2. |
| 1274 | 17805301 | During feeding, increases in circulating pancreatic insulin inhibit hepatic glucose output through the activation of the Ser/Thr kinase AKT and subsequent phosphorylation of the forkhead transcription factor FOXO1 (refs 1-3). |
| 1275 | 17805301 | Under fasting conditions, FOXO1 increases gluconeogenic gene expression in concert with the cAMP responsive coactivator TORC2 (refs 4-8). |
| 1276 | 17805301 | In response to pancreatic glucagon, TORC2 is de-phosphorylated at Ser 171 and transported to the nucleus, in which it stimulates the gluconeogenic programme by binding to CREB. |
| 1277 | 17805301 | Here we show in mice that insulin inhibits gluconeogenic gene expression during re-feeding by promoting the phosphorylation and ubiquitin-dependent degradation of TORC2. |
| 1278 | 17805301 | Insulin disrupts TORC2 activity by induction of the Ser/Thr kinase SIK2, which we show here undergoes AKT2-mediated phosphorylation at Ser 358. |
| 1279 | 17805301 | Activated SIK2 in turn stimulated the Ser 171 phosphorylation and cytoplasmic translocation of TORC2. |
| 1280 | 17805301 | Insulin modulates gluconeogenesis by inhibition of the coactivator TORC2. |
| 1281 | 17805301 | During feeding, increases in circulating pancreatic insulin inhibit hepatic glucose output through the activation of the Ser/Thr kinase AKT and subsequent phosphorylation of the forkhead transcription factor FOXO1 (refs 1-3). |
| 1282 | 17805301 | Under fasting conditions, FOXO1 increases gluconeogenic gene expression in concert with the cAMP responsive coactivator TORC2 (refs 4-8). |
| 1283 | 17805301 | In response to pancreatic glucagon, TORC2 is de-phosphorylated at Ser 171 and transported to the nucleus, in which it stimulates the gluconeogenic programme by binding to CREB. |
| 1284 | 17805301 | Here we show in mice that insulin inhibits gluconeogenic gene expression during re-feeding by promoting the phosphorylation and ubiquitin-dependent degradation of TORC2. |
| 1285 | 17805301 | Insulin disrupts TORC2 activity by induction of the Ser/Thr kinase SIK2, which we show here undergoes AKT2-mediated phosphorylation at Ser 358. |
| 1286 | 17805301 | Activated SIK2 in turn stimulated the Ser 171 phosphorylation and cytoplasmic translocation of TORC2. |
| 1287 | 17885675 | In search for the possible downstream target genes of Foxo-1, we show that when Foxo-1 expression is blocked both in cells and in mice, the level of MyoD, a myogenic factor, is increased while a muscle negative regulator GDF-8 or myostatin is suppressed. |
| 1288 | 17919188 | FoxO1 regulates beta-cell proliferation and protects against beta-cell failure induced by oxidative stress through NeuroD and MafA induction. |
| 1289 | 17919188 | In addition, FoxO1 nuclear exclusion is required for the proliferative effects of glucoincretin glucagon-like peptide-1 in islets. |
| 1290 | 17919188 | FoxO1 regulates beta-cell proliferation and protects against beta-cell failure induced by oxidative stress through NeuroD and MafA induction. |
| 1291 | 17919188 | In addition, FoxO1 nuclear exclusion is required for the proliferative effects of glucoincretin glucagon-like peptide-1 in islets. |
| 1292 | 18056789 | Chronic late-gestation hypoglycemia upregulates hepatic PEPCK associated with increased PGC1alpha mRNA and phosphorylated CREB in fetal sheep. |
| 1293 | 18056789 | Peroxisome proliferator-activated receptor-gamma coactivator-1alpha mRNA and phosphorylation of cAMP response element binding protein at Ser(133) were both increased, with no change in Akt, forkhead transcription factor FoxO1, hepatocyte nuclear factor-4alpha, or CCAAT enhancer binding protein-beta. |
| 1294 | 18162514 | The effects of OXA on cAMP, adenylate-cyclase-kinase (AKT), phosphoinositide-dependent kinase (PDK)-1, forkhead box O-1 (Foxo1), and cAMP response element-binding protein were measured by ELISA and Western blot. |
| 1295 | 18162514 | OXA decreased cAMP and Ca(2+)(i) concentration and increased AKT, PDK-1, and Foxo1 phosphorylation. |
| 1296 | 18162514 | OXA increases AKT/PDK-1 phosphorylation and inhibits proglucagon expression via phosphatidylinositol 3-kinase- and Foxo-1-dependent pathways. |
| 1297 | 18162514 | The effects of OXA on cAMP, adenylate-cyclase-kinase (AKT), phosphoinositide-dependent kinase (PDK)-1, forkhead box O-1 (Foxo1), and cAMP response element-binding protein were measured by ELISA and Western blot. |
| 1298 | 18162514 | OXA decreased cAMP and Ca(2+)(i) concentration and increased AKT, PDK-1, and Foxo1 phosphorylation. |
| 1299 | 18162514 | OXA increases AKT/PDK-1 phosphorylation and inhibits proglucagon expression via phosphatidylinositol 3-kinase- and Foxo-1-dependent pathways. |
| 1300 | 18245813 | Iron depletion improves insulin resistance in patients with nonalcoholic fatty liver disease and diabetes and also stabilizes the hypoxia-inducible factor (HIF)-1, resulting in increased glucose uptake in vitro. |
| 1301 | 18245813 | In HepG2 cells, deferoxamine stabilized HIF-1alpha and induced the constitutive glucose transporter Glut1 and the insulin receptor. |
| 1302 | 18245813 | Up-regulation of insulin receptor by deferoxamine was mimicked by the intracellular iron chelator deferasirox and the hypoxia inducer CoCl2 and required the HIF-1 obligate partner ARNT/HIF-1beta. |
| 1303 | 18245813 | Deferoxamine consistently increased the phosphorylation status of Akt/PKB and its targets FoxO1 and Gsk3beta, which mediate the effect of insulin on gluconeogenesis and glycogen synthesis, and up-regulated genes involved in glucose uptake and utilization. |
| 1304 | 18245813 | Iron depletion of Sprague-Dawley rats increased HIF-1alpha expression, improved glucose clearance, and was associated with up-regulation of insulin receptor and Akt/PKB levels and of glucose transport in hepatic tissue. |
| 1305 | 18308721 | CD36-dependent regulation of muscle FoxO1 and PDK4 in the PPAR delta/beta-mediated adaptation to metabolic stress. |
| 1306 | 18308721 | Increased fatty acid flux or enforced CD36 expression in C(2)C(12) cells is sufficient to induce FoxO1 and PDK4, whereas CD36 knockdown has opposite effects. |
| 1307 | 18308721 | In vivo, CD36 loss blunts fasting induction of FoxO1 and PDK4 and the associated suppression of glucose oxidation. |
| 1308 | 18308721 | Loss of PPARdelta/beta phenocopies CD36 deficiency in blunting fasting induction of muscle FoxO1 and PDK4 in vivo. |
| 1309 | 18308721 | FoxO1 in turn can regulate CD36, lipoprotein lipase, and PDK4, reinforcing the action of PPARdelta/beta to increase muscle reliance on FA. |
| 1310 | 18308721 | CD36-dependent regulation of muscle FoxO1 and PDK4 in the PPAR delta/beta-mediated adaptation to metabolic stress. |
| 1311 | 18308721 | Increased fatty acid flux or enforced CD36 expression in C(2)C(12) cells is sufficient to induce FoxO1 and PDK4, whereas CD36 knockdown has opposite effects. |
| 1312 | 18308721 | In vivo, CD36 loss blunts fasting induction of FoxO1 and PDK4 and the associated suppression of glucose oxidation. |
| 1313 | 18308721 | Loss of PPARdelta/beta phenocopies CD36 deficiency in blunting fasting induction of muscle FoxO1 and PDK4 in vivo. |
| 1314 | 18308721 | FoxO1 in turn can regulate CD36, lipoprotein lipase, and PDK4, reinforcing the action of PPARdelta/beta to increase muscle reliance on FA. |
| 1315 | 18308721 | CD36-dependent regulation of muscle FoxO1 and PDK4 in the PPAR delta/beta-mediated adaptation to metabolic stress. |
| 1316 | 18308721 | Increased fatty acid flux or enforced CD36 expression in C(2)C(12) cells is sufficient to induce FoxO1 and PDK4, whereas CD36 knockdown has opposite effects. |
| 1317 | 18308721 | In vivo, CD36 loss blunts fasting induction of FoxO1 and PDK4 and the associated suppression of glucose oxidation. |
| 1318 | 18308721 | Loss of PPARdelta/beta phenocopies CD36 deficiency in blunting fasting induction of muscle FoxO1 and PDK4 in vivo. |
| 1319 | 18308721 | FoxO1 in turn can regulate CD36, lipoprotein lipase, and PDK4, reinforcing the action of PPARdelta/beta to increase muscle reliance on FA. |
| 1320 | 18308721 | CD36-dependent regulation of muscle FoxO1 and PDK4 in the PPAR delta/beta-mediated adaptation to metabolic stress. |
| 1321 | 18308721 | Increased fatty acid flux or enforced CD36 expression in C(2)C(12) cells is sufficient to induce FoxO1 and PDK4, whereas CD36 knockdown has opposite effects. |
| 1322 | 18308721 | In vivo, CD36 loss blunts fasting induction of FoxO1 and PDK4 and the associated suppression of glucose oxidation. |
| 1323 | 18308721 | Loss of PPARdelta/beta phenocopies CD36 deficiency in blunting fasting induction of muscle FoxO1 and PDK4 in vivo. |
| 1324 | 18308721 | FoxO1 in turn can regulate CD36, lipoprotein lipase, and PDK4, reinforcing the action of PPARdelta/beta to increase muscle reliance on FA. |
| 1325 | 18388859 | ProF binds to the transcription factor Foxo1 (Forkhead box O1), a negative regulator of insulin action and adipogenesis, and facilitates the phosphorylation and thus inactivation of Foxo1 by Akt. |
| 1326 | 18388859 | Thus, ProF modulates Foxo1 phosphorylation by Akt, promoting adipocyte differentiation. |
| 1327 | 18388859 | ProF binds to the transcription factor Foxo1 (Forkhead box O1), a negative regulator of insulin action and adipogenesis, and facilitates the phosphorylation and thus inactivation of Foxo1 by Akt. |
| 1328 | 18388859 | Thus, ProF modulates Foxo1 phosphorylation by Akt, promoting adipocyte differentiation. |
| 1329 | 18391974 | The importance of FoxO1 in energy homeostasis is particularly striking under conditions of metabolic dysfunction or insulin resistance. |
| 1330 | 18391974 | In addition, the increase in pancreatic beta cell mass that normally occurs in response to a rise in insulin demand is blunted by nuclear FoxO1 expression. |
| 1331 | 18391974 | The importance of FoxO1 in energy homeostasis is particularly striking under conditions of metabolic dysfunction or insulin resistance. |
| 1332 | 18391974 | In addition, the increase in pancreatic beta cell mass that normally occurs in response to a rise in insulin demand is blunted by nuclear FoxO1 expression. |
| 1333 | 18403263 | Of the mammalian forkhead family members in the O class, FoxO1, FoxO3a and FoxO4 can fill a crucial void for the treatment of disorders that include aging, cancer, diabetes, infertility, neurodegeneration and immune system dysfunction. |
| 1334 | 18460817 | In comparison with the control, the mRNA levels of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase were significantly reduced and glucokinase mRNA was increased 3 h after the administration of biotin or insulin. |
| 1335 | 18460817 | In addition, forkhead box O1 and sterol regulatory element-binding protein 1c mRNA expression that was enhanced by the insulin treatment was inversely decreased by biotin. |
| 1336 | 18497885 | FoxO1 mediates insulin-dependent regulation of hepatic VLDL production in mice. |
| 1337 | 18497885 | To characterize the underlying mechanism, we studied hepatic MTP regulation by forkhead box O1 (FoxO1), a transcription factor that plays a key role in hepatic insulin signaling. |
| 1338 | 18497885 | In HepG2 cells, MTP expression was induced by FoxO1 and inhibited by exposure to insulin. |
| 1339 | 18497885 | This effect correlated with the ability of FoxO1 to bind and stimulate MTP promoter activity. |
| 1340 | 18497885 | Deletion or mutation of the FoxO1 target site within the MTP promoter disabled FoxO1 binding and resulted in abolition of insulin-dependent regulation of MTP expression. |
| 1341 | 18497885 | We generated mice that expressed a constitutively active FoxO1 transgene and found that increased FoxO1 activity was associated with enhanced MTP expression, augmented VLDL production, and elevated plasma triglyceride levels. |
| 1342 | 18497885 | In contrast, RNAi-mediated silencing of hepatic FoxO1 was associated with reduced MTP and VLDL production in adult mice. |
| 1343 | 18497885 | Furthermore, we found that hepatic FoxO1 abundance and MTP production were increased in mice with abnormal triglyceride metabolism. |
| 1344 | 18497885 | These data suggest that FoxO1 mediates insulin regulation of MTP production and that augmented MTP levels may be a causative factor for VLDL overproduction and hypertriglyceridemia in diabetes. |
| 1345 | 18497885 | FoxO1 mediates insulin-dependent regulation of hepatic VLDL production in mice. |
| 1346 | 18497885 | To characterize the underlying mechanism, we studied hepatic MTP regulation by forkhead box O1 (FoxO1), a transcription factor that plays a key role in hepatic insulin signaling. |
| 1347 | 18497885 | In HepG2 cells, MTP expression was induced by FoxO1 and inhibited by exposure to insulin. |
| 1348 | 18497885 | This effect correlated with the ability of FoxO1 to bind and stimulate MTP promoter activity. |
| 1349 | 18497885 | Deletion or mutation of the FoxO1 target site within the MTP promoter disabled FoxO1 binding and resulted in abolition of insulin-dependent regulation of MTP expression. |
| 1350 | 18497885 | We generated mice that expressed a constitutively active FoxO1 transgene and found that increased FoxO1 activity was associated with enhanced MTP expression, augmented VLDL production, and elevated plasma triglyceride levels. |
| 1351 | 18497885 | In contrast, RNAi-mediated silencing of hepatic FoxO1 was associated with reduced MTP and VLDL production in adult mice. |
| 1352 | 18497885 | Furthermore, we found that hepatic FoxO1 abundance and MTP production were increased in mice with abnormal triglyceride metabolism. |
| 1353 | 18497885 | These data suggest that FoxO1 mediates insulin regulation of MTP production and that augmented MTP levels may be a causative factor for VLDL overproduction and hypertriglyceridemia in diabetes. |
| 1354 | 18497885 | FoxO1 mediates insulin-dependent regulation of hepatic VLDL production in mice. |
| 1355 | 18497885 | To characterize the underlying mechanism, we studied hepatic MTP regulation by forkhead box O1 (FoxO1), a transcription factor that plays a key role in hepatic insulin signaling. |
| 1356 | 18497885 | In HepG2 cells, MTP expression was induced by FoxO1 and inhibited by exposure to insulin. |
| 1357 | 18497885 | This effect correlated with the ability of FoxO1 to bind and stimulate MTP promoter activity. |
| 1358 | 18497885 | Deletion or mutation of the FoxO1 target site within the MTP promoter disabled FoxO1 binding and resulted in abolition of insulin-dependent regulation of MTP expression. |
| 1359 | 18497885 | We generated mice that expressed a constitutively active FoxO1 transgene and found that increased FoxO1 activity was associated with enhanced MTP expression, augmented VLDL production, and elevated plasma triglyceride levels. |
| 1360 | 18497885 | In contrast, RNAi-mediated silencing of hepatic FoxO1 was associated with reduced MTP and VLDL production in adult mice. |
| 1361 | 18497885 | Furthermore, we found that hepatic FoxO1 abundance and MTP production were increased in mice with abnormal triglyceride metabolism. |
| 1362 | 18497885 | These data suggest that FoxO1 mediates insulin regulation of MTP production and that augmented MTP levels may be a causative factor for VLDL overproduction and hypertriglyceridemia in diabetes. |
| 1363 | 18497885 | FoxO1 mediates insulin-dependent regulation of hepatic VLDL production in mice. |
| 1364 | 18497885 | To characterize the underlying mechanism, we studied hepatic MTP regulation by forkhead box O1 (FoxO1), a transcription factor that plays a key role in hepatic insulin signaling. |
| 1365 | 18497885 | In HepG2 cells, MTP expression was induced by FoxO1 and inhibited by exposure to insulin. |
| 1366 | 18497885 | This effect correlated with the ability of FoxO1 to bind and stimulate MTP promoter activity. |
| 1367 | 18497885 | Deletion or mutation of the FoxO1 target site within the MTP promoter disabled FoxO1 binding and resulted in abolition of insulin-dependent regulation of MTP expression. |
| 1368 | 18497885 | We generated mice that expressed a constitutively active FoxO1 transgene and found that increased FoxO1 activity was associated with enhanced MTP expression, augmented VLDL production, and elevated plasma triglyceride levels. |
| 1369 | 18497885 | In contrast, RNAi-mediated silencing of hepatic FoxO1 was associated with reduced MTP and VLDL production in adult mice. |
| 1370 | 18497885 | Furthermore, we found that hepatic FoxO1 abundance and MTP production were increased in mice with abnormal triglyceride metabolism. |
| 1371 | 18497885 | These data suggest that FoxO1 mediates insulin regulation of MTP production and that augmented MTP levels may be a causative factor for VLDL overproduction and hypertriglyceridemia in diabetes. |
| 1372 | 18497885 | FoxO1 mediates insulin-dependent regulation of hepatic VLDL production in mice. |
| 1373 | 18497885 | To characterize the underlying mechanism, we studied hepatic MTP regulation by forkhead box O1 (FoxO1), a transcription factor that plays a key role in hepatic insulin signaling. |
| 1374 | 18497885 | In HepG2 cells, MTP expression was induced by FoxO1 and inhibited by exposure to insulin. |
| 1375 | 18497885 | This effect correlated with the ability of FoxO1 to bind and stimulate MTP promoter activity. |
| 1376 | 18497885 | Deletion or mutation of the FoxO1 target site within the MTP promoter disabled FoxO1 binding and resulted in abolition of insulin-dependent regulation of MTP expression. |
| 1377 | 18497885 | We generated mice that expressed a constitutively active FoxO1 transgene and found that increased FoxO1 activity was associated with enhanced MTP expression, augmented VLDL production, and elevated plasma triglyceride levels. |
| 1378 | 18497885 | In contrast, RNAi-mediated silencing of hepatic FoxO1 was associated with reduced MTP and VLDL production in adult mice. |
| 1379 | 18497885 | Furthermore, we found that hepatic FoxO1 abundance and MTP production were increased in mice with abnormal triglyceride metabolism. |
| 1380 | 18497885 | These data suggest that FoxO1 mediates insulin regulation of MTP production and that augmented MTP levels may be a causative factor for VLDL overproduction and hypertriglyceridemia in diabetes. |
| 1381 | 18497885 | FoxO1 mediates insulin-dependent regulation of hepatic VLDL production in mice. |
| 1382 | 18497885 | To characterize the underlying mechanism, we studied hepatic MTP regulation by forkhead box O1 (FoxO1), a transcription factor that plays a key role in hepatic insulin signaling. |
| 1383 | 18497885 | In HepG2 cells, MTP expression was induced by FoxO1 and inhibited by exposure to insulin. |
| 1384 | 18497885 | This effect correlated with the ability of FoxO1 to bind and stimulate MTP promoter activity. |
| 1385 | 18497885 | Deletion or mutation of the FoxO1 target site within the MTP promoter disabled FoxO1 binding and resulted in abolition of insulin-dependent regulation of MTP expression. |
| 1386 | 18497885 | We generated mice that expressed a constitutively active FoxO1 transgene and found that increased FoxO1 activity was associated with enhanced MTP expression, augmented VLDL production, and elevated plasma triglyceride levels. |
| 1387 | 18497885 | In contrast, RNAi-mediated silencing of hepatic FoxO1 was associated with reduced MTP and VLDL production in adult mice. |
| 1388 | 18497885 | Furthermore, we found that hepatic FoxO1 abundance and MTP production were increased in mice with abnormal triglyceride metabolism. |
| 1389 | 18497885 | These data suggest that FoxO1 mediates insulin regulation of MTP production and that augmented MTP levels may be a causative factor for VLDL overproduction and hypertriglyceridemia in diabetes. |
| 1390 | 18497885 | FoxO1 mediates insulin-dependent regulation of hepatic VLDL production in mice. |
| 1391 | 18497885 | To characterize the underlying mechanism, we studied hepatic MTP regulation by forkhead box O1 (FoxO1), a transcription factor that plays a key role in hepatic insulin signaling. |
| 1392 | 18497885 | In HepG2 cells, MTP expression was induced by FoxO1 and inhibited by exposure to insulin. |
| 1393 | 18497885 | This effect correlated with the ability of FoxO1 to bind and stimulate MTP promoter activity. |
| 1394 | 18497885 | Deletion or mutation of the FoxO1 target site within the MTP promoter disabled FoxO1 binding and resulted in abolition of insulin-dependent regulation of MTP expression. |
| 1395 | 18497885 | We generated mice that expressed a constitutively active FoxO1 transgene and found that increased FoxO1 activity was associated with enhanced MTP expression, augmented VLDL production, and elevated plasma triglyceride levels. |
| 1396 | 18497885 | In contrast, RNAi-mediated silencing of hepatic FoxO1 was associated with reduced MTP and VLDL production in adult mice. |
| 1397 | 18497885 | Furthermore, we found that hepatic FoxO1 abundance and MTP production were increased in mice with abnormal triglyceride metabolism. |
| 1398 | 18497885 | These data suggest that FoxO1 mediates insulin regulation of MTP production and that augmented MTP levels may be a causative factor for VLDL overproduction and hypertriglyceridemia in diabetes. |
| 1399 | 18497885 | FoxO1 mediates insulin-dependent regulation of hepatic VLDL production in mice. |
| 1400 | 18497885 | To characterize the underlying mechanism, we studied hepatic MTP regulation by forkhead box O1 (FoxO1), a transcription factor that plays a key role in hepatic insulin signaling. |
| 1401 | 18497885 | In HepG2 cells, MTP expression was induced by FoxO1 and inhibited by exposure to insulin. |
| 1402 | 18497885 | This effect correlated with the ability of FoxO1 to bind and stimulate MTP promoter activity. |
| 1403 | 18497885 | Deletion or mutation of the FoxO1 target site within the MTP promoter disabled FoxO1 binding and resulted in abolition of insulin-dependent regulation of MTP expression. |
| 1404 | 18497885 | We generated mice that expressed a constitutively active FoxO1 transgene and found that increased FoxO1 activity was associated with enhanced MTP expression, augmented VLDL production, and elevated plasma triglyceride levels. |
| 1405 | 18497885 | In contrast, RNAi-mediated silencing of hepatic FoxO1 was associated with reduced MTP and VLDL production in adult mice. |
| 1406 | 18497885 | Furthermore, we found that hepatic FoxO1 abundance and MTP production were increased in mice with abnormal triglyceride metabolism. |
| 1407 | 18497885 | These data suggest that FoxO1 mediates insulin regulation of MTP production and that augmented MTP levels may be a causative factor for VLDL overproduction and hypertriglyceridemia in diabetes. |
| 1408 | 18497885 | FoxO1 mediates insulin-dependent regulation of hepatic VLDL production in mice. |
| 1409 | 18497885 | To characterize the underlying mechanism, we studied hepatic MTP regulation by forkhead box O1 (FoxO1), a transcription factor that plays a key role in hepatic insulin signaling. |
| 1410 | 18497885 | In HepG2 cells, MTP expression was induced by FoxO1 and inhibited by exposure to insulin. |
| 1411 | 18497885 | This effect correlated with the ability of FoxO1 to bind and stimulate MTP promoter activity. |
| 1412 | 18497885 | Deletion or mutation of the FoxO1 target site within the MTP promoter disabled FoxO1 binding and resulted in abolition of insulin-dependent regulation of MTP expression. |
| 1413 | 18497885 | We generated mice that expressed a constitutively active FoxO1 transgene and found that increased FoxO1 activity was associated with enhanced MTP expression, augmented VLDL production, and elevated plasma triglyceride levels. |
| 1414 | 18497885 | In contrast, RNAi-mediated silencing of hepatic FoxO1 was associated with reduced MTP and VLDL production in adult mice. |
| 1415 | 18497885 | Furthermore, we found that hepatic FoxO1 abundance and MTP production were increased in mice with abnormal triglyceride metabolism. |
| 1416 | 18497885 | These data suggest that FoxO1 mediates insulin regulation of MTP production and that augmented MTP levels may be a causative factor for VLDL overproduction and hypertriglyceridemia in diabetes. |
| 1417 | 18511845 | TGFbeta1, TNFalpha, and insulin signaling crosstalk in regulation of the rat cholesterol 7alpha-hydroxylase gene expression. |
| 1418 | 18511845 | Previous studies show that TGFbeta1, TNFalpha, and insulin inhibit cholesterol 7alpha-hydroxylase (CYP7A1) gene transcription and bile acid synthesis in human hepatocytes. |
| 1419 | 18511845 | In this study, we investigated insulin, TGFbeta1, and TNFalpha regulation of rat Cyp7a1 gene transcription. |
| 1420 | 18511845 | Smad3, FoxO1, and HNF4alpha synergistically stimulated rat Cyp7a1 gene transcription. |
| 1421 | 18511845 | Mutations of the Smad3, FoxO1, or HNF4alpha binding site attenuated the rat Cyp7a1 promoter activity. |
| 1422 | 18511845 | Furthermore, TNFalpha and cJun attenuated TGFbeta1 stimulation of rat Cyp7a1. |
| 1423 | 18511845 | Insulin or adenovirus-mediated expression of constitutively active AKT1 inhibited FoxO1 and Smad3 synergy. |
| 1424 | 18511845 | In streptozotocin-induced diabetic rats, Cyp7a1 mRNA expression levels were induced and insulin attenuated CYP7A1 mRNA levels. |
| 1425 | 18511845 | Chromatin immunoprecipitation assay showed that FoxO1 binding to Cyp7a1 chromatin was increased in diabetic rat livers and insulin reduced FoxO1 binding. |
| 1426 | 18511845 | The crosstalk of insulin, TGFbeta and TNFalpha signaling pathways may regulate bile acid synthesis and lipid homeostasis in diabetes, fatty liver disease, and liver fibrosis. |
| 1427 | 18511845 | TGFbeta1, TNFalpha, and insulin signaling crosstalk in regulation of the rat cholesterol 7alpha-hydroxylase gene expression. |
| 1428 | 18511845 | Previous studies show that TGFbeta1, TNFalpha, and insulin inhibit cholesterol 7alpha-hydroxylase (CYP7A1) gene transcription and bile acid synthesis in human hepatocytes. |
| 1429 | 18511845 | In this study, we investigated insulin, TGFbeta1, and TNFalpha regulation of rat Cyp7a1 gene transcription. |
| 1430 | 18511845 | Smad3, FoxO1, and HNF4alpha synergistically stimulated rat Cyp7a1 gene transcription. |
| 1431 | 18511845 | Mutations of the Smad3, FoxO1, or HNF4alpha binding site attenuated the rat Cyp7a1 promoter activity. |
| 1432 | 18511845 | Furthermore, TNFalpha and cJun attenuated TGFbeta1 stimulation of rat Cyp7a1. |
| 1433 | 18511845 | Insulin or adenovirus-mediated expression of constitutively active AKT1 inhibited FoxO1 and Smad3 synergy. |
| 1434 | 18511845 | In streptozotocin-induced diabetic rats, Cyp7a1 mRNA expression levels were induced and insulin attenuated CYP7A1 mRNA levels. |
| 1435 | 18511845 | Chromatin immunoprecipitation assay showed that FoxO1 binding to Cyp7a1 chromatin was increased in diabetic rat livers and insulin reduced FoxO1 binding. |
| 1436 | 18511845 | The crosstalk of insulin, TGFbeta and TNFalpha signaling pathways may regulate bile acid synthesis and lipid homeostasis in diabetes, fatty liver disease, and liver fibrosis. |
| 1437 | 18511845 | TGFbeta1, TNFalpha, and insulin signaling crosstalk in regulation of the rat cholesterol 7alpha-hydroxylase gene expression. |
| 1438 | 18511845 | Previous studies show that TGFbeta1, TNFalpha, and insulin inhibit cholesterol 7alpha-hydroxylase (CYP7A1) gene transcription and bile acid synthesis in human hepatocytes. |
| 1439 | 18511845 | In this study, we investigated insulin, TGFbeta1, and TNFalpha regulation of rat Cyp7a1 gene transcription. |
| 1440 | 18511845 | Smad3, FoxO1, and HNF4alpha synergistically stimulated rat Cyp7a1 gene transcription. |
| 1441 | 18511845 | Mutations of the Smad3, FoxO1, or HNF4alpha binding site attenuated the rat Cyp7a1 promoter activity. |
| 1442 | 18511845 | Furthermore, TNFalpha and cJun attenuated TGFbeta1 stimulation of rat Cyp7a1. |
| 1443 | 18511845 | Insulin or adenovirus-mediated expression of constitutively active AKT1 inhibited FoxO1 and Smad3 synergy. |
| 1444 | 18511845 | In streptozotocin-induced diabetic rats, Cyp7a1 mRNA expression levels were induced and insulin attenuated CYP7A1 mRNA levels. |
| 1445 | 18511845 | Chromatin immunoprecipitation assay showed that FoxO1 binding to Cyp7a1 chromatin was increased in diabetic rat livers and insulin reduced FoxO1 binding. |
| 1446 | 18511845 | The crosstalk of insulin, TGFbeta and TNFalpha signaling pathways may regulate bile acid synthesis and lipid homeostasis in diabetes, fatty liver disease, and liver fibrosis. |
| 1447 | 18587407 | Disinhibition of the forkhead transcription factor FoxO1, increases expression of the biliary cholesterol transporters Abcg5 and Abcg8, resulting in an increase in biliary cholesterol secretion. |
| 1448 | 18587407 | Hepatic insulin resistance also decreases expression of the bile acid synthetic enzymes, particularly Cyp7b1, and produces partial resistance to the farnesoid X receptor, leading to a lithogenic bile salt profile. |
| 1449 | 18590693 | Inactivation of hepatic Foxo1 by insulin signaling is required for adaptive nutrient homeostasis and endocrine growth regulation. |
| 1450 | 18590693 | To assess the contribution of Foxo1 to metabolic dysregulation during hepatic insulin resistance, we disrupted Foxo1 expression in the liver of mice lacking hepatic Irs1 and Irs2 (DKO mice). |
| 1451 | 18590693 | DKO mice were small and developed diabetes; analysis of the DKO-liver transcriptome identified perturbed expression of growth and metabolic genes, including increased Ppargc1a and Igfbp1, and decreased glucokinase, Srebp1c, Ghr, and Igf1. |
| 1452 | 18590693 | Liver-specific deletion of Foxo1 in DKO mice resulted in significant normalization of the DKO-liver transcriptome and partial restoration of the response to fasting and feeding, near normal blood glucose and insulin concentrations, and normalization of body size. |
| 1453 | 18590693 | These results demonstrate that constitutively active Foxo1 significantly contributes to hyperglycemia during severe hepatic insulin resistance, and that the Irs1/2 --> PI3K --> Akt --> Foxo1 branch of insulin signaling is largely responsible for hepatic insulin-regulated glucose homeostasis and somatic growth. |
| 1454 | 18590693 | Inactivation of hepatic Foxo1 by insulin signaling is required for adaptive nutrient homeostasis and endocrine growth regulation. |
| 1455 | 18590693 | To assess the contribution of Foxo1 to metabolic dysregulation during hepatic insulin resistance, we disrupted Foxo1 expression in the liver of mice lacking hepatic Irs1 and Irs2 (DKO mice). |
| 1456 | 18590693 | DKO mice were small and developed diabetes; analysis of the DKO-liver transcriptome identified perturbed expression of growth and metabolic genes, including increased Ppargc1a and Igfbp1, and decreased glucokinase, Srebp1c, Ghr, and Igf1. |
| 1457 | 18590693 | Liver-specific deletion of Foxo1 in DKO mice resulted in significant normalization of the DKO-liver transcriptome and partial restoration of the response to fasting and feeding, near normal blood glucose and insulin concentrations, and normalization of body size. |
| 1458 | 18590693 | These results demonstrate that constitutively active Foxo1 significantly contributes to hyperglycemia during severe hepatic insulin resistance, and that the Irs1/2 --> PI3K --> Akt --> Foxo1 branch of insulin signaling is largely responsible for hepatic insulin-regulated glucose homeostasis and somatic growth. |
| 1459 | 18590693 | Inactivation of hepatic Foxo1 by insulin signaling is required for adaptive nutrient homeostasis and endocrine growth regulation. |
| 1460 | 18590693 | To assess the contribution of Foxo1 to metabolic dysregulation during hepatic insulin resistance, we disrupted Foxo1 expression in the liver of mice lacking hepatic Irs1 and Irs2 (DKO mice). |
| 1461 | 18590693 | DKO mice were small and developed diabetes; analysis of the DKO-liver transcriptome identified perturbed expression of growth and metabolic genes, including increased Ppargc1a and Igfbp1, and decreased glucokinase, Srebp1c, Ghr, and Igf1. |
| 1462 | 18590693 | Liver-specific deletion of Foxo1 in DKO mice resulted in significant normalization of the DKO-liver transcriptome and partial restoration of the response to fasting and feeding, near normal blood glucose and insulin concentrations, and normalization of body size. |
| 1463 | 18590693 | These results demonstrate that constitutively active Foxo1 significantly contributes to hyperglycemia during severe hepatic insulin resistance, and that the Irs1/2 --> PI3K --> Akt --> Foxo1 branch of insulin signaling is largely responsible for hepatic insulin-regulated glucose homeostasis and somatic growth. |
| 1464 | 18590693 | Inactivation of hepatic Foxo1 by insulin signaling is required for adaptive nutrient homeostasis and endocrine growth regulation. |
| 1465 | 18590693 | To assess the contribution of Foxo1 to metabolic dysregulation during hepatic insulin resistance, we disrupted Foxo1 expression in the liver of mice lacking hepatic Irs1 and Irs2 (DKO mice). |
| 1466 | 18590693 | DKO mice were small and developed diabetes; analysis of the DKO-liver transcriptome identified perturbed expression of growth and metabolic genes, including increased Ppargc1a and Igfbp1, and decreased glucokinase, Srebp1c, Ghr, and Igf1. |
| 1467 | 18590693 | Liver-specific deletion of Foxo1 in DKO mice resulted in significant normalization of the DKO-liver transcriptome and partial restoration of the response to fasting and feeding, near normal blood glucose and insulin concentrations, and normalization of body size. |
| 1468 | 18590693 | These results demonstrate that constitutively active Foxo1 significantly contributes to hyperglycemia during severe hepatic insulin resistance, and that the Irs1/2 --> PI3K --> Akt --> Foxo1 branch of insulin signaling is largely responsible for hepatic insulin-regulated glucose homeostasis and somatic growth. |
| 1469 | 18713797 | Palmitate also reduced insulin-stimulated IR and IRS-2 tyrosine phosphorylation, IRS-2-associated PI 3-kinase activity, and phosphorylation of Akt, p70 S6 kinase, GSK-3 and FOXO1A. |
| 1470 | 18927507 | FoxO1 integrates insulin signaling to VLDL production. |
| 1471 | 18927507 | Our recent studies illustrate that the forkhead transcription factor FoxO1 acts in the liver to integrate hepatic insulin action to VLDL production. |
| 1472 | 18927507 | Augmented FoxO1 activity in insulin resistant livers promotes hepatic VLDL overproduction and predisposes to the development of hypertriglyceridemia. |
| 1473 | 18927507 | FoxO1 integrates insulin signaling to VLDL production. |
| 1474 | 18927507 | Our recent studies illustrate that the forkhead transcription factor FoxO1 acts in the liver to integrate hepatic insulin action to VLDL production. |
| 1475 | 18927507 | Augmented FoxO1 activity in insulin resistant livers promotes hepatic VLDL overproduction and predisposes to the development of hypertriglyceridemia. |
| 1476 | 18927507 | FoxO1 integrates insulin signaling to VLDL production. |
| 1477 | 18927507 | Our recent studies illustrate that the forkhead transcription factor FoxO1 acts in the liver to integrate hepatic insulin action to VLDL production. |
| 1478 | 18927507 | Augmented FoxO1 activity in insulin resistant livers promotes hepatic VLDL overproduction and predisposes to the development of hypertriglyceridemia. |
| 1479 | 19237543 | FGF15/FGFR4 integrates growth factor signaling with hepatic bile acid metabolism and insulin action. |
| 1480 | 19237543 | The current studies show FGF15 signaling decreases hepatic forkhead transcription factor 1 (FoxO1) activity through phosphatidylinositol (PI) 3-kinase-dependent phosphorylation. |
| 1481 | 19237543 | The bile acid receptor FXR (farnesoid X receptor) activates expression of fibroblast growth factor (FGF) 15 in the intestine, which acts through hepatic FGFR4 to suppress cholesterol-7alpha hydroxylase (CYP7A1) and limit bile acid production. |
| 1482 | 19237543 | Because FoxO1 activity and CYP7A1 gene expression are both increased by fasting, we hypothesized CYP7A1 might be a FoxO1 target gene. |
| 1483 | 19237543 | Consistent with recently reported results, we show CYP7A1 is a direct target of FoxO1. |
| 1484 | 19237543 | FGFR4 is the major hepatic FGF receptor isoform and is responsible for the hepatic effects of FGF15. |
| 1485 | 19237543 | We also show that expression of FGFR4 in liver was decreased by fasting, increased by insulin, and reduced by streptozotocin-induced diabetes, implicating FGFR4 as a primary target of insulin regulation. |
| 1486 | 19237543 | Because insulin and FGF both target the PI 3-kinase pathway, these observations suggest FoxO1 is a key node in the convergence of FGF and insulin signaling pathways and functions as a key integrator for the regulation of glucose and bile acid metabolism. |
| 1487 | 19237543 | FGF15/FGFR4 integrates growth factor signaling with hepatic bile acid metabolism and insulin action. |
| 1488 | 19237543 | The current studies show FGF15 signaling decreases hepatic forkhead transcription factor 1 (FoxO1) activity through phosphatidylinositol (PI) 3-kinase-dependent phosphorylation. |
| 1489 | 19237543 | The bile acid receptor FXR (farnesoid X receptor) activates expression of fibroblast growth factor (FGF) 15 in the intestine, which acts through hepatic FGFR4 to suppress cholesterol-7alpha hydroxylase (CYP7A1) and limit bile acid production. |
| 1490 | 19237543 | Because FoxO1 activity and CYP7A1 gene expression are both increased by fasting, we hypothesized CYP7A1 might be a FoxO1 target gene. |
| 1491 | 19237543 | Consistent with recently reported results, we show CYP7A1 is a direct target of FoxO1. |
| 1492 | 19237543 | FGFR4 is the major hepatic FGF receptor isoform and is responsible for the hepatic effects of FGF15. |
| 1493 | 19237543 | We also show that expression of FGFR4 in liver was decreased by fasting, increased by insulin, and reduced by streptozotocin-induced diabetes, implicating FGFR4 as a primary target of insulin regulation. |
| 1494 | 19237543 | Because insulin and FGF both target the PI 3-kinase pathway, these observations suggest FoxO1 is a key node in the convergence of FGF and insulin signaling pathways and functions as a key integrator for the regulation of glucose and bile acid metabolism. |
| 1495 | 19237543 | FGF15/FGFR4 integrates growth factor signaling with hepatic bile acid metabolism and insulin action. |
| 1496 | 19237543 | The current studies show FGF15 signaling decreases hepatic forkhead transcription factor 1 (FoxO1) activity through phosphatidylinositol (PI) 3-kinase-dependent phosphorylation. |
| 1497 | 19237543 | The bile acid receptor FXR (farnesoid X receptor) activates expression of fibroblast growth factor (FGF) 15 in the intestine, which acts through hepatic FGFR4 to suppress cholesterol-7alpha hydroxylase (CYP7A1) and limit bile acid production. |
| 1498 | 19237543 | Because FoxO1 activity and CYP7A1 gene expression are both increased by fasting, we hypothesized CYP7A1 might be a FoxO1 target gene. |
| 1499 | 19237543 | Consistent with recently reported results, we show CYP7A1 is a direct target of FoxO1. |
| 1500 | 19237543 | FGFR4 is the major hepatic FGF receptor isoform and is responsible for the hepatic effects of FGF15. |
| 1501 | 19237543 | We also show that expression of FGFR4 in liver was decreased by fasting, increased by insulin, and reduced by streptozotocin-induced diabetes, implicating FGFR4 as a primary target of insulin regulation. |
| 1502 | 19237543 | Because insulin and FGF both target the PI 3-kinase pathway, these observations suggest FoxO1 is a key node in the convergence of FGF and insulin signaling pathways and functions as a key integrator for the regulation of glucose and bile acid metabolism. |
| 1503 | 19237543 | FGF15/FGFR4 integrates growth factor signaling with hepatic bile acid metabolism and insulin action. |
| 1504 | 19237543 | The current studies show FGF15 signaling decreases hepatic forkhead transcription factor 1 (FoxO1) activity through phosphatidylinositol (PI) 3-kinase-dependent phosphorylation. |
| 1505 | 19237543 | The bile acid receptor FXR (farnesoid X receptor) activates expression of fibroblast growth factor (FGF) 15 in the intestine, which acts through hepatic FGFR4 to suppress cholesterol-7alpha hydroxylase (CYP7A1) and limit bile acid production. |
| 1506 | 19237543 | Because FoxO1 activity and CYP7A1 gene expression are both increased by fasting, we hypothesized CYP7A1 might be a FoxO1 target gene. |
| 1507 | 19237543 | Consistent with recently reported results, we show CYP7A1 is a direct target of FoxO1. |
| 1508 | 19237543 | FGFR4 is the major hepatic FGF receptor isoform and is responsible for the hepatic effects of FGF15. |
| 1509 | 19237543 | We also show that expression of FGFR4 in liver was decreased by fasting, increased by insulin, and reduced by streptozotocin-induced diabetes, implicating FGFR4 as a primary target of insulin regulation. |
| 1510 | 19237543 | Because insulin and FGF both target the PI 3-kinase pathway, these observations suggest FoxO1 is a key node in the convergence of FGF and insulin signaling pathways and functions as a key integrator for the regulation of glucose and bile acid metabolism. |
| 1511 | 19254690 | Up-regulation of thioredoxin interacting protein (Txnip) by p38 MAPK and FOXO1 contributes to the impaired thioredoxin activity and increased ROS in glucose-treated endothelial cells. |
| 1512 | 19254690 | To investigate the mechanisms involved, we found that glucose enhanced the expression of thioredoxin interacting protein (Txnip), a Trx inhibitory protein, through p38 mitogen-activated protein kinase (MAPK). |
| 1513 | 19254690 | We also showed that glucose regulated Txnip at transcription level and p38 MAPK and forkhead box O1 transcriptional factor (FOXO1) were involved in the process. |
| 1514 | 19254690 | Taken together, upregulation of Txnip and subsequent impairment of thioredoxin antioxidative system through p38 MAPK and FOXO1 may represent a novel mechanism for glucose-induced increase in intracellular ROS. |
| 1515 | 19254690 | Up-regulation of thioredoxin interacting protein (Txnip) by p38 MAPK and FOXO1 contributes to the impaired thioredoxin activity and increased ROS in glucose-treated endothelial cells. |
| 1516 | 19254690 | To investigate the mechanisms involved, we found that glucose enhanced the expression of thioredoxin interacting protein (Txnip), a Trx inhibitory protein, through p38 mitogen-activated protein kinase (MAPK). |
| 1517 | 19254690 | We also showed that glucose regulated Txnip at transcription level and p38 MAPK and forkhead box O1 transcriptional factor (FOXO1) were involved in the process. |
| 1518 | 19254690 | Taken together, upregulation of Txnip and subsequent impairment of thioredoxin antioxidative system through p38 MAPK and FOXO1 may represent a novel mechanism for glucose-induced increase in intracellular ROS. |
| 1519 | 19254690 | Up-regulation of thioredoxin interacting protein (Txnip) by p38 MAPK and FOXO1 contributes to the impaired thioredoxin activity and increased ROS in glucose-treated endothelial cells. |
| 1520 | 19254690 | To investigate the mechanisms involved, we found that glucose enhanced the expression of thioredoxin interacting protein (Txnip), a Trx inhibitory protein, through p38 mitogen-activated protein kinase (MAPK). |
| 1521 | 19254690 | We also showed that glucose regulated Txnip at transcription level and p38 MAPK and forkhead box O1 transcriptional factor (FOXO1) were involved in the process. |
| 1522 | 19254690 | Taken together, upregulation of Txnip and subsequent impairment of thioredoxin antioxidative system through p38 MAPK and FOXO1 may represent a novel mechanism for glucose-induced increase in intracellular ROS. |
| 1523 | 19262508 | AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. |
| 1524 | 19262508 | Here we demonstrate that AMPK controls the expression of genes involved in energy metabolism in mouse skeletal muscle by acting in coordination with another metabolic sensor, the NAD+-dependent type III deacetylase SIRT1. |
| 1525 | 19262508 | AMPK enhances SIRT1 activity by increasing cellular NAD+ levels, resulting in the deacetylation and modulation of the activity of downstream SIRT1 targets that include the peroxisome proliferator-activated receptor-gamma coactivator 1alpha and the forkhead box O1 (FOXO1) and O3 (FOXO3a) transcription factors. |
| 1526 | 19262508 | The AMPK-induced SIRT1-mediated deacetylation of these targets explains many of the convergent biological effects of AMPK and SIRT1 on energy metabolism. |
| 1527 | 19264873 | Muscle-specific overexpression of heparin-binding epidermal growth factor-like growth factor increases peripheral glucose disposal and insulin sensitivity. |
| 1528 | 19264873 | In the present study, we found that exercise up-regulates heparin-binding epidermal growth factor-like growth factor (HB-EGF) in skeletal muscle. |
| 1529 | 19264873 | These changes were accompanied by increased kinase activity of Akt in skeletal muscle and consequent inhibition of Forkhead box O1-dependent expression of the pyruvate dehydrogenase kinase 4 gene. |
| 1530 | 19264873 | Our results suggest that HB-EGF produced by contracting muscle acts as an insulin sensitizer that facilitates peripheral glucose disposal. |
| 1531 | 19273580 | Acute exercise modulates the Foxo1/PGC-1alpha pathway in the liver of diet-induced obesity rats. |
| 1532 | 19273580 | PGC-1alpha and Foxo1 can physically interact with one another and represent an important signal transduction pathway that governs the synthesis of glucose in the liver. |
| 1533 | 19273580 | However, the effect of physical activity on PGC-1alpha/Foxo1 association is unknown. |
| 1534 | 19273580 | 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. |
| 1535 | 19273580 | Acute exercise modulates the Foxo1/PGC-1alpha pathway in the liver of diet-induced obesity rats. |
| 1536 | 19273580 | PGC-1alpha and Foxo1 can physically interact with one another and represent an important signal transduction pathway that governs the synthesis of glucose in the liver. |
| 1537 | 19273580 | However, the effect of physical activity on PGC-1alpha/Foxo1 association is unknown. |
| 1538 | 19273580 | 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. |
| 1539 | 19273580 | Acute exercise modulates the Foxo1/PGC-1alpha pathway in the liver of diet-induced obesity rats. |
| 1540 | 19273580 | PGC-1alpha and Foxo1 can physically interact with one another and represent an important signal transduction pathway that governs the synthesis of glucose in the liver. |
| 1541 | 19273580 | However, the effect of physical activity on PGC-1alpha/Foxo1 association is unknown. |
| 1542 | 19273580 | 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. |
| 1543 | 19273580 | Acute exercise modulates the Foxo1/PGC-1alpha pathway in the liver of diet-induced obesity rats. |
| 1544 | 19273580 | PGC-1alpha and Foxo1 can physically interact with one another and represent an important signal transduction pathway that governs the synthesis of glucose in the liver. |
| 1545 | 19273580 | However, the effect of physical activity on PGC-1alpha/Foxo1 association is unknown. |
| 1546 | 19273580 | 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. |
| 1547 | 19533653 | Atrogin-1, MuRF1, and FoXO, as well as phosphorylated GSK-3beta and 4E-BP1 are reduced in skeletal muscle of chronic spinal cord-injured patients. |
| 1548 | 19533653 | Therefore, the aim of this study was to determine whether there was an increase in catabolic signaling targets, such as atrogin-1, muscle ring finger-1 (MuRF1), forkhead transcription factor (FoXO), and myostatin, and decreases in anabolic signaling targets, such as insulin-like growth factor (IGF), v-akt murine thymoma viral oncogene (Akt), glycogen synthase kinase-beta (GSK-3beta), mammalian target of rapamycin (mTOR), eukaryotic initiation factor 4E binding protein 1 (4E-BP1), and p70(s6kinase) in chronic complete SCI patients. |
| 1549 | 19533653 | In SCI patients, when compared with controls, there was a significant reduction in mRNA levels of atrogin-1 (59%; P < 0.05), MuRF1 (55%; P < 0.05), and myostatin (46%; P < 0.01), and in protein levels of FoXO1 (72%; P < 0.05), FoXO3a (60%; P < 0.05), and atrogin-1 (36%; P < 0.05). |
| 1550 | 19533653 | Decreases in the protein levels of IGF-1 (48%; P < 0.001) and phosphorylated GSK-3beta (54%; P < 0.05), 4E-BP1 (48%; P < 0.05), and p70(s6kinase) (60%; P = 0.1) were also observed, the latter three in an Akt- and mTOR-independent manner. |
| 1551 | 19533653 | Reductions in atrogin-1, MuRF1, FoXO, and myostatin suggest the existence of an internal mechanism aimed at reducing further loss of muscle proteins during chronic SCI. |
| 1552 | 19533653 | The downregulation of signaling proteins that regulate anabolism, such as IGF, GSK-3beta, and 4E-BP1, would reduce the ability to increase protein synthesis rates. |
| 1553 | 19549853 | SirT1 knockdown in liver decreases basal hepatic glucose production and increases hepatic insulin responsiveness in diabetic rats. |
| 1554 | 19549853 | Because Sirtuin 1 (SirT1) induces hepatic gluconeogenesis during fasting through the induction of phosphoenolpyruvate carboxylase kinase (PEPCK), fructose-1,6-bisphosphatase (FBPase), and glucose-6-phosphatase (G6Pase) gene transcription, we hypothesized that reducing SirT1, by using an antisense oligonucleotide (ASO), would decrease fasting hyperglycemia in a rat model of T2DM. |
| 1555 | 19549853 | Whole body insulin sensitivity was also increased in the SirT1 ASO treated rats as reflected by a 25% increase in the glucose infusion rate required to maintain euglycemia during the hyperinsulinemic-euglycemic clamp and could entirely be attributed to increased suppression of hepatic glucose production by insulin. |
| 1556 | 19549853 | The reduction in basal and clamped rates of glucose production could in turn be attributed to decreased expression of PEPCK, FBPase, and G6Pase due to increased acetylation of signal transducer and activator of transcription 3 (STAT3), forkhead box O1 (FOXO1), and peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha), known substrates of SirT1. |
| 1557 | 19639221 | Bis(maltolato)-oxovanadium (IV)-induced phosphorylation of PKB, GSK-3 and FOXO1 contributes to its glucoregulatory responses (review). |
| 1558 | 19639221 | While the precise molecular mechanism by which BMOV exerts its insulin-mimetic effects remains poorly defined, studies have shown that BMOV is a potent activator of several key components of the insulin signaling pathways, such as phosphatidyl-inositol 3-kinase (PI3-K), and its downstream effector, protein kinase B (PKB). |
| 1559 | 19639221 | In addition, BMOV-induced phosphorylation of PKB has also been associated with the enhanced phosphorylation of glycogen synthase kinase-3 (GSK-3) and forkhead box protein 1 (FOXO1). |
| 1560 | 19639221 | Since PKB is instrumental in mediating the effects of insulin on glucose transport, glycogen synthesis and gluconeogenesis, it is reasonable to suggest that activation of this pathway by BMOV serves as a mechanism for its insulin-like effects. |
| 1561 | 19639221 | Bis(maltolato)-oxovanadium (IV)-induced phosphorylation of PKB, GSK-3 and FOXO1 contributes to its glucoregulatory responses (review). |
| 1562 | 19639221 | While the precise molecular mechanism by which BMOV exerts its insulin-mimetic effects remains poorly defined, studies have shown that BMOV is a potent activator of several key components of the insulin signaling pathways, such as phosphatidyl-inositol 3-kinase (PI3-K), and its downstream effector, protein kinase B (PKB). |
| 1563 | 19639221 | In addition, BMOV-induced phosphorylation of PKB has also been associated with the enhanced phosphorylation of glycogen synthase kinase-3 (GSK-3) and forkhead box protein 1 (FOXO1). |
| 1564 | 19639221 | Since PKB is instrumental in mediating the effects of insulin on glucose transport, glycogen synthesis and gluconeogenesis, it is reasonable to suggest that activation of this pathway by BMOV serves as a mechanism for its insulin-like effects. |
| 1565 | 19745063 | The transcription factor forkhead box 01 (FOXO1) was tested for mediating TNF stimulation of osteoclastogenic and inflammatory factors in bone morphogenetic protein 2 pretreated ATDC5 and C3H10T1/2 chondrogenic cells. |
| 1566 | 19745063 | FOXO1 knockdown by small-interfering RNA significantly reduced TNF-alpha, receptor activator for nuclear factor kB ligand, macrophage colony-stimulating factor, interleukin-1alpha, and interleukin-6 mRNA compared with scrambled small-interfering RNA. |
| 1567 | 19745063 | An association between FOXO1 and the TNF-alpha promoter was demonstrated by chromatin immunoprecipitation assay. |
| 1568 | 19745063 | These results suggest that diabetes-enhanced TNF-alpha increases the expression of resorptive factors in chondrocytes through a process that involves activation of FOXO1 and that TNF-alpha dysregulation leads to enhanced osteoclast formation and accelerated loss of cartilage. |
| 1569 | 19745063 | The transcription factor forkhead box 01 (FOXO1) was tested for mediating TNF stimulation of osteoclastogenic and inflammatory factors in bone morphogenetic protein 2 pretreated ATDC5 and C3H10T1/2 chondrogenic cells. |
| 1570 | 19745063 | FOXO1 knockdown by small-interfering RNA significantly reduced TNF-alpha, receptor activator for nuclear factor kB ligand, macrophage colony-stimulating factor, interleukin-1alpha, and interleukin-6 mRNA compared with scrambled small-interfering RNA. |
| 1571 | 19745063 | An association between FOXO1 and the TNF-alpha promoter was demonstrated by chromatin immunoprecipitation assay. |
| 1572 | 19745063 | These results suggest that diabetes-enhanced TNF-alpha increases the expression of resorptive factors in chondrocytes through a process that involves activation of FOXO1 and that TNF-alpha dysregulation leads to enhanced osteoclast formation and accelerated loss of cartilage. |
| 1573 | 19745063 | The transcription factor forkhead box 01 (FOXO1) was tested for mediating TNF stimulation of osteoclastogenic and inflammatory factors in bone morphogenetic protein 2 pretreated ATDC5 and C3H10T1/2 chondrogenic cells. |
| 1574 | 19745063 | FOXO1 knockdown by small-interfering RNA significantly reduced TNF-alpha, receptor activator for nuclear factor kB ligand, macrophage colony-stimulating factor, interleukin-1alpha, and interleukin-6 mRNA compared with scrambled small-interfering RNA. |
| 1575 | 19745063 | An association between FOXO1 and the TNF-alpha promoter was demonstrated by chromatin immunoprecipitation assay. |
| 1576 | 19745063 | These results suggest that diabetes-enhanced TNF-alpha increases the expression of resorptive factors in chondrocytes through a process that involves activation of FOXO1 and that TNF-alpha dysregulation leads to enhanced osteoclast formation and accelerated loss of cartilage. |
| 1577 | 19745063 | The transcription factor forkhead box 01 (FOXO1) was tested for mediating TNF stimulation of osteoclastogenic and inflammatory factors in bone morphogenetic protein 2 pretreated ATDC5 and C3H10T1/2 chondrogenic cells. |
| 1578 | 19745063 | FOXO1 knockdown by small-interfering RNA significantly reduced TNF-alpha, receptor activator for nuclear factor kB ligand, macrophage colony-stimulating factor, interleukin-1alpha, and interleukin-6 mRNA compared with scrambled small-interfering RNA. |
| 1579 | 19745063 | An association between FOXO1 and the TNF-alpha promoter was demonstrated by chromatin immunoprecipitation assay. |
| 1580 | 19745063 | These results suggest that diabetes-enhanced TNF-alpha increases the expression of resorptive factors in chondrocytes through a process that involves activation of FOXO1 and that TNF-alpha dysregulation leads to enhanced osteoclast formation and accelerated loss of cartilage. |
| 1581 | 19767734 | The obesity susceptibility gene Cpe links FoxO1 signaling in hypothalamic pro-opiomelanocortin neurons with regulation of food intake. |
| 1582 | 19767734 | Insulin and leptin inhibit food intake through actions in the central nervous system that are partly mediated by the transcription factor FoxO1. |
| 1583 | 19767734 | We show that FoxO1 ablation in pro-opiomelanocortin (Pomc)-expressing neurons in mice (here called Pomc-Foxo1(-/-) mice) increases Carboxypeptidase E (Cpe) expression, resulting in selective increases of alpha-melanocyte-stimulating hormone (alpha-Msh) and carboxy-cleaved beta-endorphin, the products of Cpe-dependent processing of Pomc. |
| 1584 | 19767734 | We show that Cpe expression is downregulated by diet-induced obesity and that FoxO1 deletion offsets the decrease, protecting against weight gain. |
| 1585 | 19767734 | Moreover, moderate Cpe overexpression in the arcuate nucleus phenocopies features of the FoxO1 mutation. |
| 1586 | 19767734 | The obesity susceptibility gene Cpe links FoxO1 signaling in hypothalamic pro-opiomelanocortin neurons with regulation of food intake. |
| 1587 | 19767734 | Insulin and leptin inhibit food intake through actions in the central nervous system that are partly mediated by the transcription factor FoxO1. |
| 1588 | 19767734 | We show that FoxO1 ablation in pro-opiomelanocortin (Pomc)-expressing neurons in mice (here called Pomc-Foxo1(-/-) mice) increases Carboxypeptidase E (Cpe) expression, resulting in selective increases of alpha-melanocyte-stimulating hormone (alpha-Msh) and carboxy-cleaved beta-endorphin, the products of Cpe-dependent processing of Pomc. |
| 1589 | 19767734 | We show that Cpe expression is downregulated by diet-induced obesity and that FoxO1 deletion offsets the decrease, protecting against weight gain. |
| 1590 | 19767734 | Moreover, moderate Cpe overexpression in the arcuate nucleus phenocopies features of the FoxO1 mutation. |
| 1591 | 19767734 | The obesity susceptibility gene Cpe links FoxO1 signaling in hypothalamic pro-opiomelanocortin neurons with regulation of food intake. |
| 1592 | 19767734 | Insulin and leptin inhibit food intake through actions in the central nervous system that are partly mediated by the transcription factor FoxO1. |
| 1593 | 19767734 | We show that FoxO1 ablation in pro-opiomelanocortin (Pomc)-expressing neurons in mice (here called Pomc-Foxo1(-/-) mice) increases Carboxypeptidase E (Cpe) expression, resulting in selective increases of alpha-melanocyte-stimulating hormone (alpha-Msh) and carboxy-cleaved beta-endorphin, the products of Cpe-dependent processing of Pomc. |
| 1594 | 19767734 | We show that Cpe expression is downregulated by diet-induced obesity and that FoxO1 deletion offsets the decrease, protecting against weight gain. |
| 1595 | 19767734 | Moreover, moderate Cpe overexpression in the arcuate nucleus phenocopies features of the FoxO1 mutation. |
| 1596 | 19767734 | The obesity susceptibility gene Cpe links FoxO1 signaling in hypothalamic pro-opiomelanocortin neurons with regulation of food intake. |
| 1597 | 19767734 | Insulin and leptin inhibit food intake through actions in the central nervous system that are partly mediated by the transcription factor FoxO1. |
| 1598 | 19767734 | We show that FoxO1 ablation in pro-opiomelanocortin (Pomc)-expressing neurons in mice (here called Pomc-Foxo1(-/-) mice) increases Carboxypeptidase E (Cpe) expression, resulting in selective increases of alpha-melanocyte-stimulating hormone (alpha-Msh) and carboxy-cleaved beta-endorphin, the products of Cpe-dependent processing of Pomc. |
| 1599 | 19767734 | We show that Cpe expression is downregulated by diet-induced obesity and that FoxO1 deletion offsets the decrease, protecting against weight gain. |
| 1600 | 19767734 | Moreover, moderate Cpe overexpression in the arcuate nucleus phenocopies features of the FoxO1 mutation. |
| 1601 | 19767734 | The obesity susceptibility gene Cpe links FoxO1 signaling in hypothalamic pro-opiomelanocortin neurons with regulation of food intake. |
| 1602 | 19767734 | Insulin and leptin inhibit food intake through actions in the central nervous system that are partly mediated by the transcription factor FoxO1. |
| 1603 | 19767734 | We show that FoxO1 ablation in pro-opiomelanocortin (Pomc)-expressing neurons in mice (here called Pomc-Foxo1(-/-) mice) increases Carboxypeptidase E (Cpe) expression, resulting in selective increases of alpha-melanocyte-stimulating hormone (alpha-Msh) and carboxy-cleaved beta-endorphin, the products of Cpe-dependent processing of Pomc. |
| 1604 | 19767734 | We show that Cpe expression is downregulated by diet-induced obesity and that FoxO1 deletion offsets the decrease, protecting against weight gain. |
| 1605 | 19767734 | Moreover, moderate Cpe overexpression in the arcuate nucleus phenocopies features of the FoxO1 mutation. |
| 1606 | 19769745 | Circulating tumour necrosis factor-alpha (TNFalpha) levels, which are elevated in obesity-associated insulin resistance and diabetes, inhibit insulin signalling at several points in the signalling cascade. |
| 1607 | 19769745 | As the transcription factor Foxa2 has been implicated, in part, in the regulation of gluconeogenic genes, we studied the effects of TNFalpha and/or insulin on its cellular status in hepatocytes, followed by an assessment of its occupancy on the phosphoenolpyruvate carboxykinase (PEPCK) promoter. |
| 1608 | 19769745 | Preincubation of cells with TNFalpha, followed by insulin, significantly prevented insulin-mediated nuclear exclusion of Foxa2 and substantially increased its nuclear concentration. |
| 1609 | 19769745 | TNFalpha alone, however, did not alter the status of cellular Foxa2 or its occupancy on the PEPCK promoter. |
| 1610 | 19769745 | TNFalpha preincubation also significantly attenuated insulin-induced inhibition of the expression of gluconeogenic enzymes and hepatic glucose production. |
| 1611 | 19769745 | Insulin inhibition of PEPCK expression and the preventive effect of TNFalpha could be partially but significantly restored in the presence of Foxa2 siRNA. |
| 1612 | 19769745 | Several other well-known mediators of insulin action in the liver in general and of gluconeogenic genes in particular include Foxo1, PGC-1 and SREBP-1c. |
| 1613 | 19769745 | Our results indicate that another transcription factor, Foxa2, is at least partly responsible for the attenuating effect of TNFalpha on insulin action on PEPCK expression and glucose production in HepG2 cells. |
| 1614 | 19837872 | Forkhead box O1/pancreatic and duodenal homeobox 1 intracellular translocation is regulated by c-Jun N-terminal kinase and involved in prostaglandin E2-induced pancreatic beta-cell dysfunction. |
| 1615 | 19837872 | We found that PGE(2) time-dependently increased the c-Jun N-terminal kinase (JNK) pathway activity. |
| 1616 | 19837872 | JNK inhibition by the JNK-specific inhibitor SP600125 reversed PGE(2)-inhibited glucose-stimulated insulin secretion (GSIS). |
| 1617 | 19837872 | PGE(2) induced dephosphorylation of Akt and FOXO1, leading to nuclear localization and transactivation of FOXO1. |
| 1618 | 19837872 | Activation of FOXO1 induced nuclear exclusion but had no obvious effect on the whole-cell protein level of pancreatic and duodenal homeobox 1 (PDX1). |
| 1619 | 19837872 | In addition, we demonstrated that DN-JNK1 but not DN-JNK2 or CA-Akt abolished the PGE(2)-induced AP-1 luciferase reporter activity, whereas DN-JNK1 and CA-Akt but not DN-JNK2 reversed the effect of PGE(2) on FOXO1 transcriptional activity, and overexpression of DN-JNK1 rescued PGE(2)-impaired GSIS in mouse islets. |
| 1620 | 19837872 | PGE(2)-mediated JNK1 activation, through dephosphorylation of Akt and FOXO1, leads to nuclear accumulation of FOXO1 and nucleocytoplasmic shuttling of PDX1, finally resulting in defective GSIS in pancreatic beta-cells. |
| 1621 | 19837872 | Forkhead box O1/pancreatic and duodenal homeobox 1 intracellular translocation is regulated by c-Jun N-terminal kinase and involved in prostaglandin E2-induced pancreatic beta-cell dysfunction. |
| 1622 | 19837872 | We found that PGE(2) time-dependently increased the c-Jun N-terminal kinase (JNK) pathway activity. |
| 1623 | 19837872 | JNK inhibition by the JNK-specific inhibitor SP600125 reversed PGE(2)-inhibited glucose-stimulated insulin secretion (GSIS). |
| 1624 | 19837872 | PGE(2) induced dephosphorylation of Akt and FOXO1, leading to nuclear localization and transactivation of FOXO1. |
| 1625 | 19837872 | Activation of FOXO1 induced nuclear exclusion but had no obvious effect on the whole-cell protein level of pancreatic and duodenal homeobox 1 (PDX1). |
| 1626 | 19837872 | In addition, we demonstrated that DN-JNK1 but not DN-JNK2 or CA-Akt abolished the PGE(2)-induced AP-1 luciferase reporter activity, whereas DN-JNK1 and CA-Akt but not DN-JNK2 reversed the effect of PGE(2) on FOXO1 transcriptional activity, and overexpression of DN-JNK1 rescued PGE(2)-impaired GSIS in mouse islets. |
| 1627 | 19837872 | PGE(2)-mediated JNK1 activation, through dephosphorylation of Akt and FOXO1, leads to nuclear accumulation of FOXO1 and nucleocytoplasmic shuttling of PDX1, finally resulting in defective GSIS in pancreatic beta-cells. |
| 1628 | 19837872 | Forkhead box O1/pancreatic and duodenal homeobox 1 intracellular translocation is regulated by c-Jun N-terminal kinase and involved in prostaglandin E2-induced pancreatic beta-cell dysfunction. |
| 1629 | 19837872 | We found that PGE(2) time-dependently increased the c-Jun N-terminal kinase (JNK) pathway activity. |
| 1630 | 19837872 | JNK inhibition by the JNK-specific inhibitor SP600125 reversed PGE(2)-inhibited glucose-stimulated insulin secretion (GSIS). |
| 1631 | 19837872 | PGE(2) induced dephosphorylation of Akt and FOXO1, leading to nuclear localization and transactivation of FOXO1. |
| 1632 | 19837872 | Activation of FOXO1 induced nuclear exclusion but had no obvious effect on the whole-cell protein level of pancreatic and duodenal homeobox 1 (PDX1). |
| 1633 | 19837872 | In addition, we demonstrated that DN-JNK1 but not DN-JNK2 or CA-Akt abolished the PGE(2)-induced AP-1 luciferase reporter activity, whereas DN-JNK1 and CA-Akt but not DN-JNK2 reversed the effect of PGE(2) on FOXO1 transcriptional activity, and overexpression of DN-JNK1 rescued PGE(2)-impaired GSIS in mouse islets. |
| 1634 | 19837872 | PGE(2)-mediated JNK1 activation, through dephosphorylation of Akt and FOXO1, leads to nuclear accumulation of FOXO1 and nucleocytoplasmic shuttling of PDX1, finally resulting in defective GSIS in pancreatic beta-cells. |
| 1635 | 19837872 | Forkhead box O1/pancreatic and duodenal homeobox 1 intracellular translocation is regulated by c-Jun N-terminal kinase and involved in prostaglandin E2-induced pancreatic beta-cell dysfunction. |
| 1636 | 19837872 | We found that PGE(2) time-dependently increased the c-Jun N-terminal kinase (JNK) pathway activity. |
| 1637 | 19837872 | JNK inhibition by the JNK-specific inhibitor SP600125 reversed PGE(2)-inhibited glucose-stimulated insulin secretion (GSIS). |
| 1638 | 19837872 | PGE(2) induced dephosphorylation of Akt and FOXO1, leading to nuclear localization and transactivation of FOXO1. |
| 1639 | 19837872 | Activation of FOXO1 induced nuclear exclusion but had no obvious effect on the whole-cell protein level of pancreatic and duodenal homeobox 1 (PDX1). |
| 1640 | 19837872 | In addition, we demonstrated that DN-JNK1 but not DN-JNK2 or CA-Akt abolished the PGE(2)-induced AP-1 luciferase reporter activity, whereas DN-JNK1 and CA-Akt but not DN-JNK2 reversed the effect of PGE(2) on FOXO1 transcriptional activity, and overexpression of DN-JNK1 rescued PGE(2)-impaired GSIS in mouse islets. |
| 1641 | 19837872 | PGE(2)-mediated JNK1 activation, through dephosphorylation of Akt and FOXO1, leads to nuclear accumulation of FOXO1 and nucleocytoplasmic shuttling of PDX1, finally resulting in defective GSIS in pancreatic beta-cells. |
| 1642 | 19837872 | Forkhead box O1/pancreatic and duodenal homeobox 1 intracellular translocation is regulated by c-Jun N-terminal kinase and involved in prostaglandin E2-induced pancreatic beta-cell dysfunction. |
| 1643 | 19837872 | We found that PGE(2) time-dependently increased the c-Jun N-terminal kinase (JNK) pathway activity. |
| 1644 | 19837872 | JNK inhibition by the JNK-specific inhibitor SP600125 reversed PGE(2)-inhibited glucose-stimulated insulin secretion (GSIS). |
| 1645 | 19837872 | PGE(2) induced dephosphorylation of Akt and FOXO1, leading to nuclear localization and transactivation of FOXO1. |
| 1646 | 19837872 | Activation of FOXO1 induced nuclear exclusion but had no obvious effect on the whole-cell protein level of pancreatic and duodenal homeobox 1 (PDX1). |
| 1647 | 19837872 | In addition, we demonstrated that DN-JNK1 but not DN-JNK2 or CA-Akt abolished the PGE(2)-induced AP-1 luciferase reporter activity, whereas DN-JNK1 and CA-Akt but not DN-JNK2 reversed the effect of PGE(2) on FOXO1 transcriptional activity, and overexpression of DN-JNK1 rescued PGE(2)-impaired GSIS in mouse islets. |
| 1648 | 19837872 | PGE(2)-mediated JNK1 activation, through dephosphorylation of Akt and FOXO1, leads to nuclear accumulation of FOXO1 and nucleocytoplasmic shuttling of PDX1, finally resulting in defective GSIS in pancreatic beta-cells. |
| 1649 | 19838201 | Foxo1 integrates insulin signaling with mitochondrial function in the liver. |
| 1650 | 19838201 | Here we used previously generated mice with hepatic insulin resistance owing to the deletion of the genes encoding insulin receptor substrate-1 (Irs-1) and Irs-2 (referred to here as double-knockout (DKO) mice) to establish the molecular link between dysregulated insulin action and mitochondrial function. |
| 1651 | 19838201 | The expression of several forkhead box O1 (Foxo1) target genes increased in the DKO liver, including heme oxygenase-1 (Hmox1), which disrupts complex III and IV of the respiratory chain and lowers the NAD(+)/NADH ratio and ATP production. |
| 1652 | 19838201 | Although peroxisome proliferator-activated receptor-gamma coactivator-1alpha (Ppargc-1alpha) was also upregulated in DKO liver, it was acetylated and failed to promote compensatory mitochondrial biogenesis or function. |
| 1653 | 19838201 | Deletion of hepatic Foxo1 in DKO liver normalized the expression of Hmox1 and the NAD(+)/NADH ratio, reduced Ppargc-1alpha acetylation and restored mitochondrial oxidative metabolism and biogenesis. |
| 1654 | 19838201 | Thus, Foxo1 integrates insulin signaling with mitochondrial function, and inhibition of Foxo1 can improve hepatic metabolism during insulin resistance and the metabolic syndrome. |
| 1655 | 19838201 | Foxo1 integrates insulin signaling with mitochondrial function in the liver. |
| 1656 | 19838201 | Here we used previously generated mice with hepatic insulin resistance owing to the deletion of the genes encoding insulin receptor substrate-1 (Irs-1) and Irs-2 (referred to here as double-knockout (DKO) mice) to establish the molecular link between dysregulated insulin action and mitochondrial function. |
| 1657 | 19838201 | The expression of several forkhead box O1 (Foxo1) target genes increased in the DKO liver, including heme oxygenase-1 (Hmox1), which disrupts complex III and IV of the respiratory chain and lowers the NAD(+)/NADH ratio and ATP production. |
| 1658 | 19838201 | Although peroxisome proliferator-activated receptor-gamma coactivator-1alpha (Ppargc-1alpha) was also upregulated in DKO liver, it was acetylated and failed to promote compensatory mitochondrial biogenesis or function. |
| 1659 | 19838201 | Deletion of hepatic Foxo1 in DKO liver normalized the expression of Hmox1 and the NAD(+)/NADH ratio, reduced Ppargc-1alpha acetylation and restored mitochondrial oxidative metabolism and biogenesis. |
| 1660 | 19838201 | Thus, Foxo1 integrates insulin signaling with mitochondrial function, and inhibition of Foxo1 can improve hepatic metabolism during insulin resistance and the metabolic syndrome. |
| 1661 | 19838201 | Foxo1 integrates insulin signaling with mitochondrial function in the liver. |
| 1662 | 19838201 | Here we used previously generated mice with hepatic insulin resistance owing to the deletion of the genes encoding insulin receptor substrate-1 (Irs-1) and Irs-2 (referred to here as double-knockout (DKO) mice) to establish the molecular link between dysregulated insulin action and mitochondrial function. |
| 1663 | 19838201 | The expression of several forkhead box O1 (Foxo1) target genes increased in the DKO liver, including heme oxygenase-1 (Hmox1), which disrupts complex III and IV of the respiratory chain and lowers the NAD(+)/NADH ratio and ATP production. |
| 1664 | 19838201 | Although peroxisome proliferator-activated receptor-gamma coactivator-1alpha (Ppargc-1alpha) was also upregulated in DKO liver, it was acetylated and failed to promote compensatory mitochondrial biogenesis or function. |
| 1665 | 19838201 | Deletion of hepatic Foxo1 in DKO liver normalized the expression of Hmox1 and the NAD(+)/NADH ratio, reduced Ppargc-1alpha acetylation and restored mitochondrial oxidative metabolism and biogenesis. |
| 1666 | 19838201 | Thus, Foxo1 integrates insulin signaling with mitochondrial function, and inhibition of Foxo1 can improve hepatic metabolism during insulin resistance and the metabolic syndrome. |
| 1667 | 19838201 | Foxo1 integrates insulin signaling with mitochondrial function in the liver. |
| 1668 | 19838201 | Here we used previously generated mice with hepatic insulin resistance owing to the deletion of the genes encoding insulin receptor substrate-1 (Irs-1) and Irs-2 (referred to here as double-knockout (DKO) mice) to establish the molecular link between dysregulated insulin action and mitochondrial function. |
| 1669 | 19838201 | The expression of several forkhead box O1 (Foxo1) target genes increased in the DKO liver, including heme oxygenase-1 (Hmox1), which disrupts complex III and IV of the respiratory chain and lowers the NAD(+)/NADH ratio and ATP production. |
| 1670 | 19838201 | Although peroxisome proliferator-activated receptor-gamma coactivator-1alpha (Ppargc-1alpha) was also upregulated in DKO liver, it was acetylated and failed to promote compensatory mitochondrial biogenesis or function. |
| 1671 | 19838201 | Deletion of hepatic Foxo1 in DKO liver normalized the expression of Hmox1 and the NAD(+)/NADH ratio, reduced Ppargc-1alpha acetylation and restored mitochondrial oxidative metabolism and biogenesis. |
| 1672 | 19838201 | Thus, Foxo1 integrates insulin signaling with mitochondrial function, and inhibition of Foxo1 can improve hepatic metabolism during insulin resistance and the metabolic syndrome. |
| 1673 | 19902175 | Impaired wound healing in mouse models of diabetes is mediated by TNF-alpha dysregulation and associated with enhanced activation of forkhead box O1 (FOXO1). |
| 1674 | 20142634 | This study was performed to establish whether only 2 sessions per week of combined aerobic and resistance exercise are enough to reduce glycated hemoglobin (HbA(1c)) and to induce changes in skeletal muscle gene expression in Type 2 diabetes mellitus (DM2) subjects with metabolic syndrome. |
| 1675 | 20142634 | There was a significant increase of mRNA of peroxisome proliferator- activated receptor (PPAR)-gamma after 6 months of train - ing (p=0.024); PPARalpha mRNA levels were significantly increased at 6 (p=0.035) and 12 months (p=0.044). |
| 1676 | 20142634 | The mRNA quantification of other genes measured [mitochondrially encoded cytochrome c oxidase subunit II (MTCO2), cytochrome c oxidase subunit Vb (COX5b), PPARgamma coactivator 1alpha (PGC- 1alpha), glucose transporter 4 (GLUT 4), forkhead transcription factor BOX O1 (FOXO-1), carnitine palmitoyltransferase 1 (CPT-1), lipoprotein lipase (LPL), and insulin receptor substrate 1 (IRS-1)] did not show significant changes at 6 and 12 months. |
| 1677 | 20142634 | This study suggests that a twice-per-week frequency of exercise is sufficient to improve glucose control and the expression of skeletal muscle PPARgamma and PPARalpha in DM2 subjects with metabolic syndrome. |
| 1678 | 20182516 | Functional recovery of diabetic mouse hearts by glutaredoxin-1 gene therapy: role of Akt-FoxO-signaling network. |
| 1679 | 20182516 | In concert, Glrx-1 prevented diabetes and ischemia-reperfusion induced reduction of cardioprotective proteins including Akt, FoxO-1, and hemeoxygenase-1, and abolished the death signal triggered by Jnk, p38 mitogen-activated protein kinase, and c-Src. |
| 1680 | 20200974 | TNF-alpha mediates diabetes-enhanced chondrocyte apoptosis during fracture healing and stimulates chondrocyte apoptosis through FOXO1. |
| 1681 | 20200974 | Tumor necrosis factor alpha (TNF-alpha) protein levels were assessed by ELISA and caspase-3 by bioactivity assay. |
| 1682 | 20200974 | In vitro studies investigated the proapoptotic transcription factor FOXO1 in regulating TNF-induced apoptosis of chondrogenic ATDC5 and C3H10T1/2 cells as representative of differentiated chondrocytes, which are important during endochondral ossification. mRNA profiling revealed an upregulation of gene sets related to apoptosis in the diabetic group on day 16 when cartilage resorption is active but not day 12 or day 22. |
| 1683 | 20200974 | This coincided with elevated TNF-alpha protein levels, chondrocyte apoptosis, enhanced caspase-3 activity, and increased FOXO1 nuclear translocation (p < .05). |
| 1684 | 20200974 | Silencing FOXO1 using siRNA in vitro significantly reduced TNF-induced apoptosis and caspase activity in differentiated chondrocytes. |
| 1685 | 20200974 | The mRNA levels of the proapoptotic genes caspase-3, caspase-8, caspase-9, and TRAIL were significantly reduced with silencing of FOXO1 in chondrocytic cells. |
| 1686 | 20200974 | Inhibiting caspase-8 and caspase-9 significantly reduced TNF-induced apoptosis in chondrogenic cells. |
| 1687 | 20200974 | Diabetes increased chondrocyte apoptosis through a mechanism that involved enhanced production of TNF-alpha, which stimulates chondrocyte apoptosis and upregulates mRNA levels of apoptotic genes through FOXO1 activation. |
| 1688 | 20200974 | TNF-alpha mediates diabetes-enhanced chondrocyte apoptosis during fracture healing and stimulates chondrocyte apoptosis through FOXO1. |
| 1689 | 20200974 | Tumor necrosis factor alpha (TNF-alpha) protein levels were assessed by ELISA and caspase-3 by bioactivity assay. |
| 1690 | 20200974 | In vitro studies investigated the proapoptotic transcription factor FOXO1 in regulating TNF-induced apoptosis of chondrogenic ATDC5 and C3H10T1/2 cells as representative of differentiated chondrocytes, which are important during endochondral ossification. mRNA profiling revealed an upregulation of gene sets related to apoptosis in the diabetic group on day 16 when cartilage resorption is active but not day 12 or day 22. |
| 1691 | 20200974 | This coincided with elevated TNF-alpha protein levels, chondrocyte apoptosis, enhanced caspase-3 activity, and increased FOXO1 nuclear translocation (p < .05). |
| 1692 | 20200974 | Silencing FOXO1 using siRNA in vitro significantly reduced TNF-induced apoptosis and caspase activity in differentiated chondrocytes. |
| 1693 | 20200974 | The mRNA levels of the proapoptotic genes caspase-3, caspase-8, caspase-9, and TRAIL were significantly reduced with silencing of FOXO1 in chondrocytic cells. |
| 1694 | 20200974 | Inhibiting caspase-8 and caspase-9 significantly reduced TNF-induced apoptosis in chondrogenic cells. |
| 1695 | 20200974 | Diabetes increased chondrocyte apoptosis through a mechanism that involved enhanced production of TNF-alpha, which stimulates chondrocyte apoptosis and upregulates mRNA levels of apoptotic genes through FOXO1 activation. |
| 1696 | 20200974 | TNF-alpha mediates diabetes-enhanced chondrocyte apoptosis during fracture healing and stimulates chondrocyte apoptosis through FOXO1. |
| 1697 | 20200974 | Tumor necrosis factor alpha (TNF-alpha) protein levels were assessed by ELISA and caspase-3 by bioactivity assay. |
| 1698 | 20200974 | In vitro studies investigated the proapoptotic transcription factor FOXO1 in regulating TNF-induced apoptosis of chondrogenic ATDC5 and C3H10T1/2 cells as representative of differentiated chondrocytes, which are important during endochondral ossification. mRNA profiling revealed an upregulation of gene sets related to apoptosis in the diabetic group on day 16 when cartilage resorption is active but not day 12 or day 22. |
| 1699 | 20200974 | This coincided with elevated TNF-alpha protein levels, chondrocyte apoptosis, enhanced caspase-3 activity, and increased FOXO1 nuclear translocation (p < .05). |
| 1700 | 20200974 | Silencing FOXO1 using siRNA in vitro significantly reduced TNF-induced apoptosis and caspase activity in differentiated chondrocytes. |
| 1701 | 20200974 | The mRNA levels of the proapoptotic genes caspase-3, caspase-8, caspase-9, and TRAIL were significantly reduced with silencing of FOXO1 in chondrocytic cells. |
| 1702 | 20200974 | Inhibiting caspase-8 and caspase-9 significantly reduced TNF-induced apoptosis in chondrogenic cells. |
| 1703 | 20200974 | Diabetes increased chondrocyte apoptosis through a mechanism that involved enhanced production of TNF-alpha, which stimulates chondrocyte apoptosis and upregulates mRNA levels of apoptotic genes through FOXO1 activation. |
| 1704 | 20200974 | TNF-alpha mediates diabetes-enhanced chondrocyte apoptosis during fracture healing and stimulates chondrocyte apoptosis through FOXO1. |
| 1705 | 20200974 | Tumor necrosis factor alpha (TNF-alpha) protein levels were assessed by ELISA and caspase-3 by bioactivity assay. |
| 1706 | 20200974 | In vitro studies investigated the proapoptotic transcription factor FOXO1 in regulating TNF-induced apoptosis of chondrogenic ATDC5 and C3H10T1/2 cells as representative of differentiated chondrocytes, which are important during endochondral ossification. mRNA profiling revealed an upregulation of gene sets related to apoptosis in the diabetic group on day 16 when cartilage resorption is active but not day 12 or day 22. |
| 1707 | 20200974 | This coincided with elevated TNF-alpha protein levels, chondrocyte apoptosis, enhanced caspase-3 activity, and increased FOXO1 nuclear translocation (p < .05). |
| 1708 | 20200974 | Silencing FOXO1 using siRNA in vitro significantly reduced TNF-induced apoptosis and caspase activity in differentiated chondrocytes. |
| 1709 | 20200974 | The mRNA levels of the proapoptotic genes caspase-3, caspase-8, caspase-9, and TRAIL were significantly reduced with silencing of FOXO1 in chondrocytic cells. |
| 1710 | 20200974 | Inhibiting caspase-8 and caspase-9 significantly reduced TNF-induced apoptosis in chondrogenic cells. |
| 1711 | 20200974 | Diabetes increased chondrocyte apoptosis through a mechanism that involved enhanced production of TNF-alpha, which stimulates chondrocyte apoptosis and upregulates mRNA levels of apoptotic genes through FOXO1 activation. |
| 1712 | 20200974 | TNF-alpha mediates diabetes-enhanced chondrocyte apoptosis during fracture healing and stimulates chondrocyte apoptosis through FOXO1. |
| 1713 | 20200974 | Tumor necrosis factor alpha (TNF-alpha) protein levels were assessed by ELISA and caspase-3 by bioactivity assay. |
| 1714 | 20200974 | In vitro studies investigated the proapoptotic transcription factor FOXO1 in regulating TNF-induced apoptosis of chondrogenic ATDC5 and C3H10T1/2 cells as representative of differentiated chondrocytes, which are important during endochondral ossification. mRNA profiling revealed an upregulation of gene sets related to apoptosis in the diabetic group on day 16 when cartilage resorption is active but not day 12 or day 22. |
| 1715 | 20200974 | This coincided with elevated TNF-alpha protein levels, chondrocyte apoptosis, enhanced caspase-3 activity, and increased FOXO1 nuclear translocation (p < .05). |
| 1716 | 20200974 | Silencing FOXO1 using siRNA in vitro significantly reduced TNF-induced apoptosis and caspase activity in differentiated chondrocytes. |
| 1717 | 20200974 | The mRNA levels of the proapoptotic genes caspase-3, caspase-8, caspase-9, and TRAIL were significantly reduced with silencing of FOXO1 in chondrocytic cells. |
| 1718 | 20200974 | Inhibiting caspase-8 and caspase-9 significantly reduced TNF-induced apoptosis in chondrogenic cells. |
| 1719 | 20200974 | Diabetes increased chondrocyte apoptosis through a mechanism that involved enhanced production of TNF-alpha, which stimulates chondrocyte apoptosis and upregulates mRNA levels of apoptotic genes through FOXO1 activation. |
| 1720 | 20200974 | TNF-alpha mediates diabetes-enhanced chondrocyte apoptosis during fracture healing and stimulates chondrocyte apoptosis through FOXO1. |
| 1721 | 20200974 | Tumor necrosis factor alpha (TNF-alpha) protein levels were assessed by ELISA and caspase-3 by bioactivity assay. |
| 1722 | 20200974 | In vitro studies investigated the proapoptotic transcription factor FOXO1 in regulating TNF-induced apoptosis of chondrogenic ATDC5 and C3H10T1/2 cells as representative of differentiated chondrocytes, which are important during endochondral ossification. mRNA profiling revealed an upregulation of gene sets related to apoptosis in the diabetic group on day 16 when cartilage resorption is active but not day 12 or day 22. |
| 1723 | 20200974 | This coincided with elevated TNF-alpha protein levels, chondrocyte apoptosis, enhanced caspase-3 activity, and increased FOXO1 nuclear translocation (p < .05). |
| 1724 | 20200974 | Silencing FOXO1 using siRNA in vitro significantly reduced TNF-induced apoptosis and caspase activity in differentiated chondrocytes. |
| 1725 | 20200974 | The mRNA levels of the proapoptotic genes caspase-3, caspase-8, caspase-9, and TRAIL were significantly reduced with silencing of FOXO1 in chondrocytic cells. |
| 1726 | 20200974 | Inhibiting caspase-8 and caspase-9 significantly reduced TNF-induced apoptosis in chondrogenic cells. |
| 1727 | 20200974 | Diabetes increased chondrocyte apoptosis through a mechanism that involved enhanced production of TNF-alpha, which stimulates chondrocyte apoptosis and upregulates mRNA levels of apoptotic genes through FOXO1 activation. |
| 1728 | 20429429 | With this in mind, our concluding chapter for Forkhead Transcription Factors: Vital Elements in Biology andMedicine offers to highlight both the diversity and complexity of the forkhead transcription family by focusing upon the mammalian forkhead transcription factors of the O class (FoxOs) that include FoxO1, FoxO3, FoxO4, and FoxO6. |
| 1729 | 20501667 | We speculated that hyperinsulinemia minimized glucose-mediated VLDL changes and performed hyperglycemic-hypoinsulinemic clamp studies in which insulin was clamped near fasting levels with somatostatin (17 mm blood glucose, 0.25 mU/kg . min insulin). |
| 1730 | 20501667 | Under low-insulin conditions, serum VLDL levels were increased 4.7-fold after hyperglycemia, and forkhead box O1 (FoxO1) was not excluded from the nucleus of liver cells. |
| 1731 | 20501667 | We tested the extent that impaired inactivation of FoxO1 by insulin was sufficient for glucose to promote increased serum VLDL. |
| 1732 | 20501667 | We found that, when the ability of insulin to inactivate FoxO1 is blocked after adenoviral delivery of constitutively active FoxO1, glucose increased serum VLDL triglyceride when given both by ip glucose tolerance testing (3.5-fold increase) and by a hyperglycemic clamp (4.6-fold). |
| 1733 | 20501667 | Under both experimental conditions in which insulin signaling to FoxO1 was impaired, we found increased activation of carbohydrate response element binding protein. |
| 1734 | 20501667 | These data suggest that glucose more potently promotes increased serum VLDL when insulin action is impaired, with either low insulin levels or disrupted downstream signaling to the transcription factor FoxO1. |
| 1735 | 20501667 | We speculated that hyperinsulinemia minimized glucose-mediated VLDL changes and performed hyperglycemic-hypoinsulinemic clamp studies in which insulin was clamped near fasting levels with somatostatin (17 mm blood glucose, 0.25 mU/kg . min insulin). |
| 1736 | 20501667 | Under low-insulin conditions, serum VLDL levels were increased 4.7-fold after hyperglycemia, and forkhead box O1 (FoxO1) was not excluded from the nucleus of liver cells. |
| 1737 | 20501667 | We tested the extent that impaired inactivation of FoxO1 by insulin was sufficient for glucose to promote increased serum VLDL. |
| 1738 | 20501667 | We found that, when the ability of insulin to inactivate FoxO1 is blocked after adenoviral delivery of constitutively active FoxO1, glucose increased serum VLDL triglyceride when given both by ip glucose tolerance testing (3.5-fold increase) and by a hyperglycemic clamp (4.6-fold). |
| 1739 | 20501667 | Under both experimental conditions in which insulin signaling to FoxO1 was impaired, we found increased activation of carbohydrate response element binding protein. |
| 1740 | 20501667 | These data suggest that glucose more potently promotes increased serum VLDL when insulin action is impaired, with either low insulin levels or disrupted downstream signaling to the transcription factor FoxO1. |
| 1741 | 20501667 | We speculated that hyperinsulinemia minimized glucose-mediated VLDL changes and performed hyperglycemic-hypoinsulinemic clamp studies in which insulin was clamped near fasting levels with somatostatin (17 mm blood glucose, 0.25 mU/kg . min insulin). |
| 1742 | 20501667 | Under low-insulin conditions, serum VLDL levels were increased 4.7-fold after hyperglycemia, and forkhead box O1 (FoxO1) was not excluded from the nucleus of liver cells. |
| 1743 | 20501667 | We tested the extent that impaired inactivation of FoxO1 by insulin was sufficient for glucose to promote increased serum VLDL. |
| 1744 | 20501667 | We found that, when the ability of insulin to inactivate FoxO1 is blocked after adenoviral delivery of constitutively active FoxO1, glucose increased serum VLDL triglyceride when given both by ip glucose tolerance testing (3.5-fold increase) and by a hyperglycemic clamp (4.6-fold). |
| 1745 | 20501667 | Under both experimental conditions in which insulin signaling to FoxO1 was impaired, we found increased activation of carbohydrate response element binding protein. |
| 1746 | 20501667 | These data suggest that glucose more potently promotes increased serum VLDL when insulin action is impaired, with either low insulin levels or disrupted downstream signaling to the transcription factor FoxO1. |
| 1747 | 20501667 | We speculated that hyperinsulinemia minimized glucose-mediated VLDL changes and performed hyperglycemic-hypoinsulinemic clamp studies in which insulin was clamped near fasting levels with somatostatin (17 mm blood glucose, 0.25 mU/kg . min insulin). |
| 1748 | 20501667 | Under low-insulin conditions, serum VLDL levels were increased 4.7-fold after hyperglycemia, and forkhead box O1 (FoxO1) was not excluded from the nucleus of liver cells. |
| 1749 | 20501667 | We tested the extent that impaired inactivation of FoxO1 by insulin was sufficient for glucose to promote increased serum VLDL. |
| 1750 | 20501667 | We found that, when the ability of insulin to inactivate FoxO1 is blocked after adenoviral delivery of constitutively active FoxO1, glucose increased serum VLDL triglyceride when given both by ip glucose tolerance testing (3.5-fold increase) and by a hyperglycemic clamp (4.6-fold). |
| 1751 | 20501667 | Under both experimental conditions in which insulin signaling to FoxO1 was impaired, we found increased activation of carbohydrate response element binding protein. |
| 1752 | 20501667 | These data suggest that glucose more potently promotes increased serum VLDL when insulin action is impaired, with either low insulin levels or disrupted downstream signaling to the transcription factor FoxO1. |
| 1753 | 20501667 | We speculated that hyperinsulinemia minimized glucose-mediated VLDL changes and performed hyperglycemic-hypoinsulinemic clamp studies in which insulin was clamped near fasting levels with somatostatin (17 mm blood glucose, 0.25 mU/kg . min insulin). |
| 1754 | 20501667 | Under low-insulin conditions, serum VLDL levels were increased 4.7-fold after hyperglycemia, and forkhead box O1 (FoxO1) was not excluded from the nucleus of liver cells. |
| 1755 | 20501667 | We tested the extent that impaired inactivation of FoxO1 by insulin was sufficient for glucose to promote increased serum VLDL. |
| 1756 | 20501667 | We found that, when the ability of insulin to inactivate FoxO1 is blocked after adenoviral delivery of constitutively active FoxO1, glucose increased serum VLDL triglyceride when given both by ip glucose tolerance testing (3.5-fold increase) and by a hyperglycemic clamp (4.6-fold). |
| 1757 | 20501667 | Under both experimental conditions in which insulin signaling to FoxO1 was impaired, we found increased activation of carbohydrate response element binding protein. |
| 1758 | 20501667 | These data suggest that glucose more potently promotes increased serum VLDL when insulin action is impaired, with either low insulin levels or disrupted downstream signaling to the transcription factor FoxO1. |
| 1759 | 20501674 | FoxO1 links hepatic insulin action to endoplasmic reticulum stress. |
| 1760 | 20501674 | Forkhead box O1 (FoxO1) is a transcription factor that mediates the inhibitory effect of insulin on target genes in hepatic metabolism. |
| 1761 | 20501674 | 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. |
| 1762 | 20501674 | FoxO1-ADA is a constitutively active allele that is refractory to insulin inhibition, allowing us to determine the metabolic effect of a dislodged FoxO1 feedback loop in mice. |
| 1763 | 20501674 | Unexpectedly, hepatic FoxO1-ADA production elicited a profound unfolded protein response, culminating in the induction of hepatic glucose-regulated protein 78 (GRP78) expression. |
| 1764 | 20501674 | FoxO1 targeted GRP78 gene for trans-activation via selective binding to an insulin responsive element in the GRP78 promoter. |
| 1765 | 20501674 | Our studies underscore the importance of an IR and IRS2-dependent feedback loop to keep FoxO1 activity in check for maintaining hepatic glycogen homeostasis and promoting adaptive unfolded protein response in response to altered metabolism and insulin action. |
| 1766 | 20501674 | Excessive FoxO1 activity, resulting from a dislodged FoxO1 feedback loop in insulin resistant liver, is attributable to hepatic endoplasmic reticulum stress and metabolic abnormalities in diabetes. |
| 1767 | 20501674 | FoxO1 links hepatic insulin action to endoplasmic reticulum stress. |
| 1768 | 20501674 | Forkhead box O1 (FoxO1) is a transcription factor that mediates the inhibitory effect of insulin on target genes in hepatic metabolism. |
| 1769 | 20501674 | 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. |
| 1770 | 20501674 | FoxO1-ADA is a constitutively active allele that is refractory to insulin inhibition, allowing us to determine the metabolic effect of a dislodged FoxO1 feedback loop in mice. |
| 1771 | 20501674 | Unexpectedly, hepatic FoxO1-ADA production elicited a profound unfolded protein response, culminating in the induction of hepatic glucose-regulated protein 78 (GRP78) expression. |
| 1772 | 20501674 | FoxO1 targeted GRP78 gene for trans-activation via selective binding to an insulin responsive element in the GRP78 promoter. |
| 1773 | 20501674 | Our studies underscore the importance of an IR and IRS2-dependent feedback loop to keep FoxO1 activity in check for maintaining hepatic glycogen homeostasis and promoting adaptive unfolded protein response in response to altered metabolism and insulin action. |
| 1774 | 20501674 | Excessive FoxO1 activity, resulting from a dislodged FoxO1 feedback loop in insulin resistant liver, is attributable to hepatic endoplasmic reticulum stress and metabolic abnormalities in diabetes. |
| 1775 | 20501674 | FoxO1 links hepatic insulin action to endoplasmic reticulum stress. |
| 1776 | 20501674 | Forkhead box O1 (FoxO1) is a transcription factor that mediates the inhibitory effect of insulin on target genes in hepatic metabolism. |
| 1777 | 20501674 | 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. |
| 1778 | 20501674 | FoxO1-ADA is a constitutively active allele that is refractory to insulin inhibition, allowing us to determine the metabolic effect of a dislodged FoxO1 feedback loop in mice. |
| 1779 | 20501674 | Unexpectedly, hepatic FoxO1-ADA production elicited a profound unfolded protein response, culminating in the induction of hepatic glucose-regulated protein 78 (GRP78) expression. |
| 1780 | 20501674 | FoxO1 targeted GRP78 gene for trans-activation via selective binding to an insulin responsive element in the GRP78 promoter. |
| 1781 | 20501674 | Our studies underscore the importance of an IR and IRS2-dependent feedback loop to keep FoxO1 activity in check for maintaining hepatic glycogen homeostasis and promoting adaptive unfolded protein response in response to altered metabolism and insulin action. |
| 1782 | 20501674 | Excessive FoxO1 activity, resulting from a dislodged FoxO1 feedback loop in insulin resistant liver, is attributable to hepatic endoplasmic reticulum stress and metabolic abnormalities in diabetes. |
| 1783 | 20501674 | FoxO1 links hepatic insulin action to endoplasmic reticulum stress. |
| 1784 | 20501674 | Forkhead box O1 (FoxO1) is a transcription factor that mediates the inhibitory effect of insulin on target genes in hepatic metabolism. |
| 1785 | 20501674 | 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. |
| 1786 | 20501674 | FoxO1-ADA is a constitutively active allele that is refractory to insulin inhibition, allowing us to determine the metabolic effect of a dislodged FoxO1 feedback loop in mice. |
| 1787 | 20501674 | Unexpectedly, hepatic FoxO1-ADA production elicited a profound unfolded protein response, culminating in the induction of hepatic glucose-regulated protein 78 (GRP78) expression. |
| 1788 | 20501674 | FoxO1 targeted GRP78 gene for trans-activation via selective binding to an insulin responsive element in the GRP78 promoter. |
| 1789 | 20501674 | Our studies underscore the importance of an IR and IRS2-dependent feedback loop to keep FoxO1 activity in check for maintaining hepatic glycogen homeostasis and promoting adaptive unfolded protein response in response to altered metabolism and insulin action. |
| 1790 | 20501674 | Excessive FoxO1 activity, resulting from a dislodged FoxO1 feedback loop in insulin resistant liver, is attributable to hepatic endoplasmic reticulum stress and metabolic abnormalities in diabetes. |
| 1791 | 20501674 | FoxO1 links hepatic insulin action to endoplasmic reticulum stress. |
| 1792 | 20501674 | Forkhead box O1 (FoxO1) is a transcription factor that mediates the inhibitory effect of insulin on target genes in hepatic metabolism. |
| 1793 | 20501674 | 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. |
| 1794 | 20501674 | FoxO1-ADA is a constitutively active allele that is refractory to insulin inhibition, allowing us to determine the metabolic effect of a dislodged FoxO1 feedback loop in mice. |
| 1795 | 20501674 | Unexpectedly, hepatic FoxO1-ADA production elicited a profound unfolded protein response, culminating in the induction of hepatic glucose-regulated protein 78 (GRP78) expression. |
| 1796 | 20501674 | FoxO1 targeted GRP78 gene for trans-activation via selective binding to an insulin responsive element in the GRP78 promoter. |
| 1797 | 20501674 | Our studies underscore the importance of an IR and IRS2-dependent feedback loop to keep FoxO1 activity in check for maintaining hepatic glycogen homeostasis and promoting adaptive unfolded protein response in response to altered metabolism and insulin action. |
| 1798 | 20501674 | Excessive FoxO1 activity, resulting from a dislodged FoxO1 feedback loop in insulin resistant liver, is attributable to hepatic endoplasmic reticulum stress and metabolic abnormalities in diabetes. |
| 1799 | 20501674 | FoxO1 links hepatic insulin action to endoplasmic reticulum stress. |
| 1800 | 20501674 | Forkhead box O1 (FoxO1) is a transcription factor that mediates the inhibitory effect of insulin on target genes in hepatic metabolism. |
| 1801 | 20501674 | 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. |
| 1802 | 20501674 | FoxO1-ADA is a constitutively active allele that is refractory to insulin inhibition, allowing us to determine the metabolic effect of a dislodged FoxO1 feedback loop in mice. |
| 1803 | 20501674 | Unexpectedly, hepatic FoxO1-ADA production elicited a profound unfolded protein response, culminating in the induction of hepatic glucose-regulated protein 78 (GRP78) expression. |
| 1804 | 20501674 | FoxO1 targeted GRP78 gene for trans-activation via selective binding to an insulin responsive element in the GRP78 promoter. |
| 1805 | 20501674 | Our studies underscore the importance of an IR and IRS2-dependent feedback loop to keep FoxO1 activity in check for maintaining hepatic glycogen homeostasis and promoting adaptive unfolded protein response in response to altered metabolism and insulin action. |
| 1806 | 20501674 | Excessive FoxO1 activity, resulting from a dislodged FoxO1 feedback loop in insulin resistant liver, is attributable to hepatic endoplasmic reticulum stress and metabolic abnormalities in diabetes. |
| 1807 | 20501674 | FoxO1 links hepatic insulin action to endoplasmic reticulum stress. |
| 1808 | 20501674 | Forkhead box O1 (FoxO1) is a transcription factor that mediates the inhibitory effect of insulin on target genes in hepatic metabolism. |
| 1809 | 20501674 | 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. |
| 1810 | 20501674 | FoxO1-ADA is a constitutively active allele that is refractory to insulin inhibition, allowing us to determine the metabolic effect of a dislodged FoxO1 feedback loop in mice. |
| 1811 | 20501674 | Unexpectedly, hepatic FoxO1-ADA production elicited a profound unfolded protein response, culminating in the induction of hepatic glucose-regulated protein 78 (GRP78) expression. |
| 1812 | 20501674 | FoxO1 targeted GRP78 gene for trans-activation via selective binding to an insulin responsive element in the GRP78 promoter. |
| 1813 | 20501674 | Our studies underscore the importance of an IR and IRS2-dependent feedback loop to keep FoxO1 activity in check for maintaining hepatic glycogen homeostasis and promoting adaptive unfolded protein response in response to altered metabolism and insulin action. |
| 1814 | 20501674 | Excessive FoxO1 activity, resulting from a dislodged FoxO1 feedback loop in insulin resistant liver, is attributable to hepatic endoplasmic reticulum stress and metabolic abnormalities in diabetes. |
| 1815 | 20655898 | Recent evidence suggests that the forkhead transcription factor Foxo1 plays an important role in the regulation of glucose and triglyceride metabolism at the gene transcription level for glucose-6 phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK), and apolipoprotein C-III (apoC-III). |
| 1816 | 20921625 | Recent studies show that MAPK phosphatase-3 (MKP-3) promotes gluconeogenic gene transcription in hepatoma cells, but little is known about the physiological role of MKP-3 in vivo. |
| 1817 | 20921625 | In vitro experiments identified forkhead box O1 (FOXO1) as a substrate for MKP-3. |
| 1818 | 20921625 | MKP-3-mediated dephosphorylation of FOXO1 at Ser256 promoted its nuclear translocation and subsequent recruitment to the promoters of key gluconeogenic genes. |
| 1819 | 20921625 | In addition, we showed that PPARγ coactivator-1α (PGC-1α) acted downstream of FOXO1 to mediate MKP-3-induced gluconeogenesis. |
| 1820 | 20921625 | Recent studies show that MAPK phosphatase-3 (MKP-3) promotes gluconeogenic gene transcription in hepatoma cells, but little is known about the physiological role of MKP-3 in vivo. |
| 1821 | 20921625 | In vitro experiments identified forkhead box O1 (FOXO1) as a substrate for MKP-3. |
| 1822 | 20921625 | MKP-3-mediated dephosphorylation of FOXO1 at Ser256 promoted its nuclear translocation and subsequent recruitment to the promoters of key gluconeogenic genes. |
| 1823 | 20921625 | In addition, we showed that PPARγ coactivator-1α (PGC-1α) acted downstream of FOXO1 to mediate MKP-3-induced gluconeogenesis. |
| 1824 | 20921625 | Recent studies show that MAPK phosphatase-3 (MKP-3) promotes gluconeogenic gene transcription in hepatoma cells, but little is known about the physiological role of MKP-3 in vivo. |
| 1825 | 20921625 | In vitro experiments identified forkhead box O1 (FOXO1) as a substrate for MKP-3. |
| 1826 | 20921625 | MKP-3-mediated dephosphorylation of FOXO1 at Ser256 promoted its nuclear translocation and subsequent recruitment to the promoters of key gluconeogenic genes. |
| 1827 | 20921625 | In addition, we showed that PPARγ coactivator-1α (PGC-1α) acted downstream of FOXO1 to mediate MKP-3-induced gluconeogenesis. |
| 1828 | 21104447 | RT-PCR was employed to detect 18 FOX family members including FOXO1, FOXO3, FOXM1, and FOXL1 in normal mouse liver. |
| 1829 | 21104447 | Results showed that all the 18 Fox genes were expressed in the normal mouse liver, among which the expression of FOXO1 and FOXO3 were found to be the highest. |
| 1830 | 21104447 | The inflammation and proliferation-related FOX family genes were found to be dynamically changed during BDL-induced liver injury with reduced FOXO1 and enhanced FOXOL1 and FOXM1, indicating their potential involvement in the pathogenesis of liver fibrosis. |
| 1831 | 21104447 | RT-PCR was employed to detect 18 FOX family members including FOXO1, FOXO3, FOXM1, and FOXL1 in normal mouse liver. |
| 1832 | 21104447 | Results showed that all the 18 Fox genes were expressed in the normal mouse liver, among which the expression of FOXO1 and FOXO3 were found to be the highest. |
| 1833 | 21104447 | The inflammation and proliferation-related FOX family genes were found to be dynamically changed during BDL-induced liver injury with reduced FOXO1 and enhanced FOXOL1 and FOXM1, indicating their potential involvement in the pathogenesis of liver fibrosis. |
| 1834 | 21104447 | RT-PCR was employed to detect 18 FOX family members including FOXO1, FOXO3, FOXM1, and FOXL1 in normal mouse liver. |
| 1835 | 21104447 | Results showed that all the 18 Fox genes were expressed in the normal mouse liver, among which the expression of FOXO1 and FOXO3 were found to be the highest. |
| 1836 | 21104447 | The inflammation and proliferation-related FOX family genes were found to be dynamically changed during BDL-induced liver injury with reduced FOXO1 and enhanced FOXOL1 and FOXM1, indicating their potential involvement in the pathogenesis of liver fibrosis. |
| 1837 | 21152033 | Multiple roles for the non-coding RNA SRA in regulation of adipogenesis and insulin sensitivity. |
| 1838 | 21152033 | Overexpression of SRA in ST2 mesenchymal precursor cells promotes their differentiation into adipocytes. |
| 1839 | 21152033 | Microarray analysis reveals hundreds of SRA-responsive genes in adipocytes, including genes involved in the cell cycle, and insulin and TNFα signaling pathways. |
| 1840 | 21152033 | SRA in adipocytes increases both glucose uptake and phosphorylation of Akt and FOXO1 in response to insulin. |
| 1841 | 21152033 | SRA promotes S-phase entry during mitotic clonal expansion, decreases expression of the cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1, and increases phosphorylation of Cdk1/Cdc2. |
| 1842 | 21152033 | SRA also inhibits the expression of adipocyte-related inflammatory genes and TNFα-induced phosphorylation of c-Jun NH(2)-terminal kinase. |
| 1843 | 21152033 | In conclusion, SRA enhances adipogenesis and adipocyte function through multiple pathways. |
| 1844 | 21177856 | Protein kinase A-alpha directly phosphorylates FoxO1 in vascular endothelial cells to regulate expression of vascular cellular adhesion molecule-1 mRNA. |
| 1845 | 21177856 | FoxO1, a forkhead box O class transcription factor, is abundant in insulin-responsive tissues. |
| 1846 | 21177856 | Akt, downstream from phosphatidylinositol 3-kinase in insulin signaling, phosphorylates FoxO1 at Thr(24), Ser(256), and Ser(319), negatively regulating its function. |
| 1847 | 21177856 | We previously reported that dehydroepiandrosterone-stimulated phosphorylation of FoxO1 in endothelial cells requires cAMP-dependent protein kinase α (PKA-α). |
| 1848 | 21177856 | Using an immune complex kinase assay with [γ-(32)P]ATP, purified PKA-α directly phosphorylated wild-type FoxO1 but not FoxO1-AAA (mutant with alanine substitutions at known Akt phosphorylation sites). |
| 1849 | 21177856 | Protein kinase A-alpha directly phosphorylates FoxO1 in vascular endothelial cells to regulate expression of vascular cellular adhesion molecule-1 mRNA. |
| 1850 | 21177856 | FoxO1, a forkhead box O class transcription factor, is abundant in insulin-responsive tissues. |
| 1851 | 21177856 | Akt, downstream from phosphatidylinositol 3-kinase in insulin signaling, phosphorylates FoxO1 at Thr(24), Ser(256), and Ser(319), negatively regulating its function. |
| 1852 | 21177856 | We previously reported that dehydroepiandrosterone-stimulated phosphorylation of FoxO1 in endothelial cells requires cAMP-dependent protein kinase α (PKA-α). |
| 1853 | 21177856 | Using an immune complex kinase assay with [γ-(32)P]ATP, purified PKA-α directly phosphorylated wild-type FoxO1 but not FoxO1-AAA (mutant with alanine substitutions at known Akt phosphorylation sites). |
| 1854 | 21177856 | Protein kinase A-alpha directly phosphorylates FoxO1 in vascular endothelial cells to regulate expression of vascular cellular adhesion molecule-1 mRNA. |
| 1855 | 21177856 | FoxO1, a forkhead box O class transcription factor, is abundant in insulin-responsive tissues. |
| 1856 | 21177856 | Akt, downstream from phosphatidylinositol 3-kinase in insulin signaling, phosphorylates FoxO1 at Thr(24), Ser(256), and Ser(319), negatively regulating its function. |
| 1857 | 21177856 | We previously reported that dehydroepiandrosterone-stimulated phosphorylation of FoxO1 in endothelial cells requires cAMP-dependent protein kinase α (PKA-α). |
| 1858 | 21177856 | Using an immune complex kinase assay with [γ-(32)P]ATP, purified PKA-α directly phosphorylated wild-type FoxO1 but not FoxO1-AAA (mutant with alanine substitutions at known Akt phosphorylation sites). |
| 1859 | 21177856 | Protein kinase A-alpha directly phosphorylates FoxO1 in vascular endothelial cells to regulate expression of vascular cellular adhesion molecule-1 mRNA. |
| 1860 | 21177856 | FoxO1, a forkhead box O class transcription factor, is abundant in insulin-responsive tissues. |
| 1861 | 21177856 | Akt, downstream from phosphatidylinositol 3-kinase in insulin signaling, phosphorylates FoxO1 at Thr(24), Ser(256), and Ser(319), negatively regulating its function. |
| 1862 | 21177856 | We previously reported that dehydroepiandrosterone-stimulated phosphorylation of FoxO1 in endothelial cells requires cAMP-dependent protein kinase α (PKA-α). |
| 1863 | 21177856 | Using an immune complex kinase assay with [γ-(32)P]ATP, purified PKA-α directly phosphorylated wild-type FoxO1 but not FoxO1-AAA (mutant with alanine substitutions at known Akt phosphorylation sites). |
| 1864 | 21177856 | Protein kinase A-alpha directly phosphorylates FoxO1 in vascular endothelial cells to regulate expression of vascular cellular adhesion molecule-1 mRNA. |
| 1865 | 21177856 | FoxO1, a forkhead box O class transcription factor, is abundant in insulin-responsive tissues. |
| 1866 | 21177856 | Akt, downstream from phosphatidylinositol 3-kinase in insulin signaling, phosphorylates FoxO1 at Thr(24), Ser(256), and Ser(319), negatively regulating its function. |
| 1867 | 21177856 | We previously reported that dehydroepiandrosterone-stimulated phosphorylation of FoxO1 in endothelial cells requires cAMP-dependent protein kinase α (PKA-α). |
| 1868 | 21177856 | Using an immune complex kinase assay with [γ-(32)P]ATP, purified PKA-α directly phosphorylated wild-type FoxO1 but not FoxO1-AAA (mutant with alanine substitutions at known Akt phosphorylation sites). |
| 1869 | 21189358 | To provide a comprehensive understanding of how GC affect adipose tissue and adipocyte function, we analyzed patterns of gene expression (HG U95 Affymetrix arrays) after culture of abdominal subcutaneous (Abd sc) and omental (Om) adipose tissues from severely obese subjects (3 F, 1 M) in the presence of insulin or insulin (7 nM) plus dexamethasone (Dex, 25 nM) for 7 days. |
| 1870 | 21189358 | Dex suppressed genes in immune/inflammatory (IL-6, IL-8, and MCP-1, expressed in nonadipocytes) and proapoptotic pathways, yet induced genes related to the acute-phase response (SAA, factor D, haptoglobin, and RBP4, expressed in adipocytes) and stress/defense response. |
| 1871 | 21189358 | Functional classification analysis showed that Dex also induced expression levels of 22 transcription factors related to insulin action and lipogenesis (LXRα, STAT5α, SREBP1, and FoxO1) and immunity/adipogenesis (TSC22D3) while suppressing 17 transcription factors in both depots. |
| 1872 | 21239445 | IGF-I induces skeletal muscle hypertrophy by stimulating protein synthesis and suppressing the protein degradation pathway; the downstream signaling pathways Akt-mammalian target of rapamycin (mTOR)-p70-kDA-S6-kinase (p70S6K), and Forkhead box O1 (FoxO1) play essential roles in this regulation. |
| 1873 | 21239445 | While treatment with H(2)O(2) significantly enhanced IGF-I-induced phosphorylation of the IGF-I receptor (IGF-IR), IGF-IR phosphorylation was markedly attenuated when cells were treated with antioxidants. |
| 1874 | 21239445 | Furthermore, the phosphorylation of FoxO1 by IGF-I decreased concomitantly with the restoration of the expression of its target genes, Atrogin-1 and muscle RING finger 1, which are related to muscle atrophy. |
| 1875 | 21239445 | Nox4 knockdown, which is reportedly to produce ROS in insulin signaling, attenuated IGF-I-induced IGF-IR phosphorylation, indicating that Nox4 is involved in the regulation of IGF-I signaling. |
| 1876 | 21239445 | IGF-I induces skeletal muscle hypertrophy by stimulating protein synthesis and suppressing the protein degradation pathway; the downstream signaling pathways Akt-mammalian target of rapamycin (mTOR)-p70-kDA-S6-kinase (p70S6K), and Forkhead box O1 (FoxO1) play essential roles in this regulation. |
| 1877 | 21239445 | While treatment with H(2)O(2) significantly enhanced IGF-I-induced phosphorylation of the IGF-I receptor (IGF-IR), IGF-IR phosphorylation was markedly attenuated when cells were treated with antioxidants. |
| 1878 | 21239445 | Furthermore, the phosphorylation of FoxO1 by IGF-I decreased concomitantly with the restoration of the expression of its target genes, Atrogin-1 and muscle RING finger 1, which are related to muscle atrophy. |
| 1879 | 21239445 | Nox4 knockdown, which is reportedly to produce ROS in insulin signaling, attenuated IGF-I-induced IGF-IR phosphorylation, indicating that Nox4 is involved in the regulation of IGF-I signaling. |
| 1880 | 21255808 | Glucagon-like peptide-1 (GLP-1) and angiotensin II type 1 receptor blocker reduce β-cell apoptosis in diabetes, but the underlying mechanisms are not fully understood. |
| 1881 | 21255808 | We examined the combination effects of GLP-1 and candesartan, an angiotensin II type 1 receptor blocker, on glucolipotoxicity-induced β-cell apoptosis; and we explored the possible mechanisms of the antiapoptotic effects. |
| 1882 | 21255808 | The effects of GLP-1 and/or candesartan on glucolipotoxicity-induced apoptosis and the phosphorylation of insulin receptor substrate-2 (IRS-2), protein kinase B (PKB), and forkhead box O1 (FoxO1) were evaluated by using MIN6 cells and isolated mouse pancreatic islets. |
| 1883 | 21255808 | Whereas palmitate significantly decreased the phosphorylation of IRS-2, PKB, and FoxO1 in MIN6 cells, these changes were significantly inhibited by treatment with GLP-1 and/or candesartan. |
| 1884 | 21255808 | In addition, wortmannin, an inhibitor of phosphoinositide 3-kinase, markedly inhibited GLP-1- and/or candesartan-mediated PKB and FoxO1 phosphorylation. |
| 1885 | 21255808 | The present results suggest that GLP-1 and candesartan additively prevent glucolipotoxicity-induced apoptosis in pancreatic β-cells through the IRS-2/phosphoinositide 3-kinase/PKB/FoxO1 signaling pathway. |
| 1886 | 21255808 | Glucagon-like peptide-1 (GLP-1) and angiotensin II type 1 receptor blocker reduce β-cell apoptosis in diabetes, but the underlying mechanisms are not fully understood. |
| 1887 | 21255808 | We examined the combination effects of GLP-1 and candesartan, an angiotensin II type 1 receptor blocker, on glucolipotoxicity-induced β-cell apoptosis; and we explored the possible mechanisms of the antiapoptotic effects. |
| 1888 | 21255808 | The effects of GLP-1 and/or candesartan on glucolipotoxicity-induced apoptosis and the phosphorylation of insulin receptor substrate-2 (IRS-2), protein kinase B (PKB), and forkhead box O1 (FoxO1) were evaluated by using MIN6 cells and isolated mouse pancreatic islets. |
| 1889 | 21255808 | Whereas palmitate significantly decreased the phosphorylation of IRS-2, PKB, and FoxO1 in MIN6 cells, these changes were significantly inhibited by treatment with GLP-1 and/or candesartan. |
| 1890 | 21255808 | In addition, wortmannin, an inhibitor of phosphoinositide 3-kinase, markedly inhibited GLP-1- and/or candesartan-mediated PKB and FoxO1 phosphorylation. |
| 1891 | 21255808 | The present results suggest that GLP-1 and candesartan additively prevent glucolipotoxicity-induced apoptosis in pancreatic β-cells through the IRS-2/phosphoinositide 3-kinase/PKB/FoxO1 signaling pathway. |
| 1892 | 21255808 | Glucagon-like peptide-1 (GLP-1) and angiotensin II type 1 receptor blocker reduce β-cell apoptosis in diabetes, but the underlying mechanisms are not fully understood. |
| 1893 | 21255808 | We examined the combination effects of GLP-1 and candesartan, an angiotensin II type 1 receptor blocker, on glucolipotoxicity-induced β-cell apoptosis; and we explored the possible mechanisms of the antiapoptotic effects. |
| 1894 | 21255808 | The effects of GLP-1 and/or candesartan on glucolipotoxicity-induced apoptosis and the phosphorylation of insulin receptor substrate-2 (IRS-2), protein kinase B (PKB), and forkhead box O1 (FoxO1) were evaluated by using MIN6 cells and isolated mouse pancreatic islets. |
| 1895 | 21255808 | Whereas palmitate significantly decreased the phosphorylation of IRS-2, PKB, and FoxO1 in MIN6 cells, these changes were significantly inhibited by treatment with GLP-1 and/or candesartan. |
| 1896 | 21255808 | In addition, wortmannin, an inhibitor of phosphoinositide 3-kinase, markedly inhibited GLP-1- and/or candesartan-mediated PKB and FoxO1 phosphorylation. |
| 1897 | 21255808 | The present results suggest that GLP-1 and candesartan additively prevent glucolipotoxicity-induced apoptosis in pancreatic β-cells through the IRS-2/phosphoinositide 3-kinase/PKB/FoxO1 signaling pathway. |
| 1898 | 21255808 | Glucagon-like peptide-1 (GLP-1) and angiotensin II type 1 receptor blocker reduce β-cell apoptosis in diabetes, but the underlying mechanisms are not fully understood. |
| 1899 | 21255808 | We examined the combination effects of GLP-1 and candesartan, an angiotensin II type 1 receptor blocker, on glucolipotoxicity-induced β-cell apoptosis; and we explored the possible mechanisms of the antiapoptotic effects. |
| 1900 | 21255808 | The effects of GLP-1 and/or candesartan on glucolipotoxicity-induced apoptosis and the phosphorylation of insulin receptor substrate-2 (IRS-2), protein kinase B (PKB), and forkhead box O1 (FoxO1) were evaluated by using MIN6 cells and isolated mouse pancreatic islets. |
| 1901 | 21255808 | Whereas palmitate significantly decreased the phosphorylation of IRS-2, PKB, and FoxO1 in MIN6 cells, these changes were significantly inhibited by treatment with GLP-1 and/or candesartan. |
| 1902 | 21255808 | In addition, wortmannin, an inhibitor of phosphoinositide 3-kinase, markedly inhibited GLP-1- and/or candesartan-mediated PKB and FoxO1 phosphorylation. |
| 1903 | 21255808 | The present results suggest that GLP-1 and candesartan additively prevent glucolipotoxicity-induced apoptosis in pancreatic β-cells through the IRS-2/phosphoinositide 3-kinase/PKB/FoxO1 signaling pathway. |
| 1904 | 21304897 | The mechanisms involve in activation of adenosine monophosphate activated protein kinase (AMPK) and improvement of insulin sensitivity. |
| 1905 | 21304897 | Gluconeogenic genes, Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose-6-phosphatase (G6Pase), were decreased in liver by BBR. |
| 1906 | 21304897 | Activities of transcription factors including Forkhead transcription factor O1 (FoxO1), sterol regulatory element-binding protein 1c (SREBP1) and carbohydrate responsive element-binding protein (ChREBP) were decreased. |
| 1907 | 21317886 | To date, the only known role of the spliced form of X-box-binding protein-1 (XBP-1s) in metabolic processes has been its ability to act as a transcription factor that regulates the expression of genes that increase the endoplasmic reticulum (ER) folding capacity, thereby improving insulin sensitivity. |
| 1908 | 21317886 | Our results thus provide the first evidence to our knowledge that XBP-1s, through its interaction with FoxO1, can bypass hepatic insulin resistance independent of its effects on ER folding capacity, suggesting a new therapeutic approach for the treatment of type 2 diabetes. |
| 1909 | 21335550 | FoxO1 activity is tightly controlled by phosphatidylinositol 3-kinase (PI3K) signaling, resulting in its phosphorylation and nuclear exclusion. |
| 1910 | 21335550 | We sought here to determine the mechanisms involved in glucose and insulin-stimulated nuclear shuttling of FoxO1 in pancreatic β cells and its consequences for preproinsulin (Ins1, Ins2) gene expression. |
| 1911 | 21335550 | Constitutively active PI3K or protein kinase B/Akt exerted similar effects, while inhibitors of PI3K, but not of glycogen synthase kinase-3 or p70 S6 kinase, blocked nuclear export. |
| 1912 | 21335550 | FoxO1 overexpression reversed the activation by glucose of pancreatic duodenum homeobox-1 (Pdx1) transcription. |
| 1913 | 21335550 | A 915-bp glucose-responsive Ins2 promoter was inhibited by constitutively active FoxO1, an effect unaltered by simultaneous overexpression of PDX1. |
| 1914 | 21335550 | 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. |
| 1915 | 21335550 | FoxO1 activity is tightly controlled by phosphatidylinositol 3-kinase (PI3K) signaling, resulting in its phosphorylation and nuclear exclusion. |
| 1916 | 21335550 | We sought here to determine the mechanisms involved in glucose and insulin-stimulated nuclear shuttling of FoxO1 in pancreatic β cells and its consequences for preproinsulin (Ins1, Ins2) gene expression. |
| 1917 | 21335550 | Constitutively active PI3K or protein kinase B/Akt exerted similar effects, while inhibitors of PI3K, but not of glycogen synthase kinase-3 or p70 S6 kinase, blocked nuclear export. |
| 1918 | 21335550 | FoxO1 overexpression reversed the activation by glucose of pancreatic duodenum homeobox-1 (Pdx1) transcription. |
| 1919 | 21335550 | A 915-bp glucose-responsive Ins2 promoter was inhibited by constitutively active FoxO1, an effect unaltered by simultaneous overexpression of PDX1. |
| 1920 | 21335550 | 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. |
| 1921 | 21335550 | FoxO1 activity is tightly controlled by phosphatidylinositol 3-kinase (PI3K) signaling, resulting in its phosphorylation and nuclear exclusion. |
| 1922 | 21335550 | We sought here to determine the mechanisms involved in glucose and insulin-stimulated nuclear shuttling of FoxO1 in pancreatic β cells and its consequences for preproinsulin (Ins1, Ins2) gene expression. |
| 1923 | 21335550 | Constitutively active PI3K or protein kinase B/Akt exerted similar effects, while inhibitors of PI3K, but not of glycogen synthase kinase-3 or p70 S6 kinase, blocked nuclear export. |
| 1924 | 21335550 | FoxO1 overexpression reversed the activation by glucose of pancreatic duodenum homeobox-1 (Pdx1) transcription. |
| 1925 | 21335550 | A 915-bp glucose-responsive Ins2 promoter was inhibited by constitutively active FoxO1, an effect unaltered by simultaneous overexpression of PDX1. |
| 1926 | 21335550 | 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. |
| 1927 | 21335550 | FoxO1 activity is tightly controlled by phosphatidylinositol 3-kinase (PI3K) signaling, resulting in its phosphorylation and nuclear exclusion. |
| 1928 | 21335550 | We sought here to determine the mechanisms involved in glucose and insulin-stimulated nuclear shuttling of FoxO1 in pancreatic β cells and its consequences for preproinsulin (Ins1, Ins2) gene expression. |
| 1929 | 21335550 | Constitutively active PI3K or protein kinase B/Akt exerted similar effects, while inhibitors of PI3K, but not of glycogen synthase kinase-3 or p70 S6 kinase, blocked nuclear export. |
| 1930 | 21335550 | FoxO1 overexpression reversed the activation by glucose of pancreatic duodenum homeobox-1 (Pdx1) transcription. |
| 1931 | 21335550 | A 915-bp glucose-responsive Ins2 promoter was inhibited by constitutively active FoxO1, an effect unaltered by simultaneous overexpression of PDX1. |
| 1932 | 21335550 | 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. |
| 1933 | 21335550 | FoxO1 activity is tightly controlled by phosphatidylinositol 3-kinase (PI3K) signaling, resulting in its phosphorylation and nuclear exclusion. |
| 1934 | 21335550 | We sought here to determine the mechanisms involved in glucose and insulin-stimulated nuclear shuttling of FoxO1 in pancreatic β cells and its consequences for preproinsulin (Ins1, Ins2) gene expression. |
| 1935 | 21335550 | Constitutively active PI3K or protein kinase B/Akt exerted similar effects, while inhibitors of PI3K, but not of glycogen synthase kinase-3 or p70 S6 kinase, blocked nuclear export. |
| 1936 | 21335550 | FoxO1 overexpression reversed the activation by glucose of pancreatic duodenum homeobox-1 (Pdx1) transcription. |
| 1937 | 21335550 | A 915-bp glucose-responsive Ins2 promoter was inhibited by constitutively active FoxO1, an effect unaltered by simultaneous overexpression of PDX1. |
| 1938 | 21335550 | 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. |
| 1939 | 21335995 | Especially milk and whey protein-based products contribute to elevations of postprandial insulin and basal insulin-like growth factor-I (IGF-I) plasma levels. |
| 1940 | 21335995 | Whey proteins are most potent inducers of glucose-dependent insulinotropic polypeptide secreted by enteroendocrine K cells which in concert with hydrolyzed whey protein-derived essential amino acids stimulate insulin secretion of pancreatic β-cells. |
| 1941 | 21335995 | Increased insulin/IGF-I signaling activates the phosphoinositide-3 kinase/Akt pathway, thereby reducing the nuclear content of the transcription factor FoxO1, the key nutrigenomic regulator of acne target genes. |
| 1942 | 21335995 | Nuclear FoxO1 deficiency has been linked to all major factors of acne pathogenesis, i.e. androgen receptor transactivation, comedogenesis, increased sebaceous lipogenesis, and follicular inflammation. |
| 1943 | 21335995 | Especially milk and whey protein-based products contribute to elevations of postprandial insulin and basal insulin-like growth factor-I (IGF-I) plasma levels. |
| 1944 | 21335995 | Whey proteins are most potent inducers of glucose-dependent insulinotropic polypeptide secreted by enteroendocrine K cells which in concert with hydrolyzed whey protein-derived essential amino acids stimulate insulin secretion of pancreatic β-cells. |
| 1945 | 21335995 | Increased insulin/IGF-I signaling activates the phosphoinositide-3 kinase/Akt pathway, thereby reducing the nuclear content of the transcription factor FoxO1, the key nutrigenomic regulator of acne target genes. |
| 1946 | 21335995 | Nuclear FoxO1 deficiency has been linked to all major factors of acne pathogenesis, i.e. androgen receptor transactivation, comedogenesis, increased sebaceous lipogenesis, and follicular inflammation. |
| 1947 | 21354306 | Insulin receptor substrate-1 and -2 mediate resistance to glucose-induced caspase-3 activation in human neuroblastoma cells. |
| 1948 | 21354306 | Insulin and insulin-like growth factor-1 (IGF-1) receptor signaling inhibits glucose-induced caspase-3 activation and apoptotic cell death. |
| 1949 | 21354306 | Even though all IRS proteins have similar function and structure, recent data suggest different actions of IRS-1 and IRS-2 in mediating their anti-apoptotic effects in glucose neurotoxicity. |
| 1950 | 21354306 | We therefore investigated the role of IRS-1/-2 in glucose-induced caspase-3 activation using human neuroblastoma cells. |
| 1951 | 21354306 | Overexpression of IRS-1 or IRS-2 caused complete resistance to glucose-induced caspase-3 cleavage. |
| 1952 | 21354306 | Inhibition of PI3-kinase reversed this protective effect of IRS-1 or IRS-2. |
| 1953 | 21354306 | IRS overexpression increased MnSOD abundance as well as BAD phosphorylation while Bim and BAX levels remained unchanged. |
| 1954 | 21354306 | Since Akt promotes cell survival at least partially via phosphorylation and inhibition of downstream forkhead box-O (FoxO) transcription factors, we generated neuroblastoma cells stably overexpressing a dominant negative mutant of FoxO1 mimicking activation of the insulin/IGF-1 pathway on FoxO-mediated transcription. |
| 1955 | 21354306 | Using these cells we showed that FoxO1 is not involved in neuronal protection mediated by increased IRS-1/-2 expression. |
| 1956 | 21354306 | Thus, overexpression of both IRS-1 and IRS-2 induces complete resistance to glucose-induced caspase-3 activation via PI3-kinase mediated BAD phosphorylation and MnSOD expression independent of FoxO1. |
| 1957 | 21354306 | Insulin receptor substrate-1 and -2 mediate resistance to glucose-induced caspase-3 activation in human neuroblastoma cells. |
| 1958 | 21354306 | Insulin and insulin-like growth factor-1 (IGF-1) receptor signaling inhibits glucose-induced caspase-3 activation and apoptotic cell death. |
| 1959 | 21354306 | Even though all IRS proteins have similar function and structure, recent data suggest different actions of IRS-1 and IRS-2 in mediating their anti-apoptotic effects in glucose neurotoxicity. |
| 1960 | 21354306 | We therefore investigated the role of IRS-1/-2 in glucose-induced caspase-3 activation using human neuroblastoma cells. |
| 1961 | 21354306 | Overexpression of IRS-1 or IRS-2 caused complete resistance to glucose-induced caspase-3 cleavage. |
| 1962 | 21354306 | Inhibition of PI3-kinase reversed this protective effect of IRS-1 or IRS-2. |
| 1963 | 21354306 | IRS overexpression increased MnSOD abundance as well as BAD phosphorylation while Bim and BAX levels remained unchanged. |
| 1964 | 21354306 | Since Akt promotes cell survival at least partially via phosphorylation and inhibition of downstream forkhead box-O (FoxO) transcription factors, we generated neuroblastoma cells stably overexpressing a dominant negative mutant of FoxO1 mimicking activation of the insulin/IGF-1 pathway on FoxO-mediated transcription. |
| 1965 | 21354306 | Using these cells we showed that FoxO1 is not involved in neuronal protection mediated by increased IRS-1/-2 expression. |
| 1966 | 21354306 | Thus, overexpression of both IRS-1 and IRS-2 induces complete resistance to glucose-induced caspase-3 activation via PI3-kinase mediated BAD phosphorylation and MnSOD expression independent of FoxO1. |
| 1967 | 21354306 | Insulin receptor substrate-1 and -2 mediate resistance to glucose-induced caspase-3 activation in human neuroblastoma cells. |
| 1968 | 21354306 | Insulin and insulin-like growth factor-1 (IGF-1) receptor signaling inhibits glucose-induced caspase-3 activation and apoptotic cell death. |
| 1969 | 21354306 | Even though all IRS proteins have similar function and structure, recent data suggest different actions of IRS-1 and IRS-2 in mediating their anti-apoptotic effects in glucose neurotoxicity. |
| 1970 | 21354306 | We therefore investigated the role of IRS-1/-2 in glucose-induced caspase-3 activation using human neuroblastoma cells. |
| 1971 | 21354306 | Overexpression of IRS-1 or IRS-2 caused complete resistance to glucose-induced caspase-3 cleavage. |
| 1972 | 21354306 | Inhibition of PI3-kinase reversed this protective effect of IRS-1 or IRS-2. |
| 1973 | 21354306 | IRS overexpression increased MnSOD abundance as well as BAD phosphorylation while Bim and BAX levels remained unchanged. |
| 1974 | 21354306 | Since Akt promotes cell survival at least partially via phosphorylation and inhibition of downstream forkhead box-O (FoxO) transcription factors, we generated neuroblastoma cells stably overexpressing a dominant negative mutant of FoxO1 mimicking activation of the insulin/IGF-1 pathway on FoxO-mediated transcription. |
| 1975 | 21354306 | Using these cells we showed that FoxO1 is not involved in neuronal protection mediated by increased IRS-1/-2 expression. |
| 1976 | 21354306 | Thus, overexpression of both IRS-1 and IRS-2 induces complete resistance to glucose-induced caspase-3 activation via PI3-kinase mediated BAD phosphorylation and MnSOD expression independent of FoxO1. |
| 1977 | 21442235 | Association analyses between the genetic polymorphisms of HNF4A and FOXO1 genes and Chinese Han patients with type 2 diabetes. |
| 1978 | 21442235 | The hepatocyte nuclear factor 4-alpha (HNF4A) and human forkhead box O1 (FOXO1) genes have been discovered to be associated with type 2 diabetes (T2D) in different populations. |
| 1979 | 21442235 | This study aimed to evaluate the association between HNF4A and FOXO1 genetic polymorphisms and type 2 diabetes in the Chinese Han population. |
| 1980 | 21442235 | Six single-nucleotide polymorphisms (SNPs) in HNF4A and seven in FOXO1 were selected and genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or TaqMan(®) technology. |
| 1981 | 21442235 | Moreover, the authors confirmed the results of previous studies for the interaction between HNF4A and FOXO1 in the pathogenesis of type 2 diabetes. |
| 1982 | 21442235 | Association analyses between the genetic polymorphisms of HNF4A and FOXO1 genes and Chinese Han patients with type 2 diabetes. |
| 1983 | 21442235 | The hepatocyte nuclear factor 4-alpha (HNF4A) and human forkhead box O1 (FOXO1) genes have been discovered to be associated with type 2 diabetes (T2D) in different populations. |
| 1984 | 21442235 | This study aimed to evaluate the association between HNF4A and FOXO1 genetic polymorphisms and type 2 diabetes in the Chinese Han population. |
| 1985 | 21442235 | Six single-nucleotide polymorphisms (SNPs) in HNF4A and seven in FOXO1 were selected and genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or TaqMan(®) technology. |
| 1986 | 21442235 | Moreover, the authors confirmed the results of previous studies for the interaction between HNF4A and FOXO1 in the pathogenesis of type 2 diabetes. |
| 1987 | 21442235 | Association analyses between the genetic polymorphisms of HNF4A and FOXO1 genes and Chinese Han patients with type 2 diabetes. |
| 1988 | 21442235 | The hepatocyte nuclear factor 4-alpha (HNF4A) and human forkhead box O1 (FOXO1) genes have been discovered to be associated with type 2 diabetes (T2D) in different populations. |
| 1989 | 21442235 | This study aimed to evaluate the association between HNF4A and FOXO1 genetic polymorphisms and type 2 diabetes in the Chinese Han population. |
| 1990 | 21442235 | Six single-nucleotide polymorphisms (SNPs) in HNF4A and seven in FOXO1 were selected and genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or TaqMan(®) technology. |
| 1991 | 21442235 | Moreover, the authors confirmed the results of previous studies for the interaction between HNF4A and FOXO1 in the pathogenesis of type 2 diabetes. |
| 1992 | 21442235 | Association analyses between the genetic polymorphisms of HNF4A and FOXO1 genes and Chinese Han patients with type 2 diabetes. |
| 1993 | 21442235 | The hepatocyte nuclear factor 4-alpha (HNF4A) and human forkhead box O1 (FOXO1) genes have been discovered to be associated with type 2 diabetes (T2D) in different populations. |
| 1994 | 21442235 | This study aimed to evaluate the association between HNF4A and FOXO1 genetic polymorphisms and type 2 diabetes in the Chinese Han population. |
| 1995 | 21442235 | Six single-nucleotide polymorphisms (SNPs) in HNF4A and seven in FOXO1 were selected and genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or TaqMan(®) technology. |
| 1996 | 21442235 | Moreover, the authors confirmed the results of previous studies for the interaction between HNF4A and FOXO1 in the pathogenesis of type 2 diabetes. |
| 1997 | 21442235 | Association analyses between the genetic polymorphisms of HNF4A and FOXO1 genes and Chinese Han patients with type 2 diabetes. |
| 1998 | 21442235 | The hepatocyte nuclear factor 4-alpha (HNF4A) and human forkhead box O1 (FOXO1) genes have been discovered to be associated with type 2 diabetes (T2D) in different populations. |
| 1999 | 21442235 | This study aimed to evaluate the association between HNF4A and FOXO1 genetic polymorphisms and type 2 diabetes in the Chinese Han population. |
| 2000 | 21442235 | Six single-nucleotide polymorphisms (SNPs) in HNF4A and seven in FOXO1 were selected and genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or TaqMan(®) technology. |
| 2001 | 21442235 | Moreover, the authors confirmed the results of previous studies for the interaction between HNF4A and FOXO1 in the pathogenesis of type 2 diabetes. |
| 2002 | 21443460 | The four members of the FOXO family (FOXO1, FOXO3A, FOXO4 and FOXO6) have distinct but overlapping cellular functions, although they seem to bind a common set of DNA sites. |
| 2003 | 21497580 | When applied at doses of 1 μM, only selenite and MSeA were capable of delaying insulin-induced phosphorylation of protein kinase B (Akt) and attenuating insulin-induced phosphorylation of forkhead box class O transcription factors FoxO1a and FoxO3. |
| 2004 | 21497580 | Even though all tested Se compounds strongly stimulated expression/activity of the cellular selenoproteins glutathione peroxidase 1 and selenoprotein W, selenite and MSeA were the most efficiently utilized Se donors. |
| 2005 | 21646544 | Pharmacological and genetic interventions revealed that insulin regulates GLUT4 and FoxO1 through the PI3-kinase isoform p110α, although FoxO1 showed higher sensitivity to p110α activity than GLUT4. |
| 2006 | 21646544 | Transient down-regulation and overexpression of Akt isoforms in adipocytes demonstrated that insulin-activated PI3-kinase signals to GLUT4 primarily through Akt2 kinase, whereas Akt1 and Akt2 signal to FoxO1. |
| 2007 | 21697492 | Here, using Huh-7.5 cells either harboring HCV-1b RNA replicons or infected with HCV-2a, we showed that HCV transcriptionally upregulated the genes for phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase), the rate-limiting enzymes for hepatic gluconeogenesis. |
| 2008 | 21697492 | PEPCK and G6Pase gene expressions are controlled by the transcription factor forkhead box O1 (FoxO1). |
| 2009 | 21697492 | It was unlikely that the decreased level of FoxO1 phosphorylation was mediated through Akt inactivation, as we observed an increased phosphorylation of Akt at Ser473 in HCV-infected cells compared to control cells. |
| 2010 | 21697492 | By using specific inhibitors of c-Jun N-terminal kinase (JNK) and reactive oxygen species (ROS), we demonstrated that HCV infection induced JNK activation via increased mitochondrial ROS production, resulting in decreased FoxO1 phosphorylation, FoxO1 nuclear accumulation, and, eventually, increased glucose production. |
| 2011 | 21697492 | We also found that HCV NS5A mediated increased ROS production and JNK activation, which is directly linked with the FoxO1-dependent increased gluconeogenesis. |
| 2012 | 21697492 | Here, using Huh-7.5 cells either harboring HCV-1b RNA replicons or infected with HCV-2a, we showed that HCV transcriptionally upregulated the genes for phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase), the rate-limiting enzymes for hepatic gluconeogenesis. |
| 2013 | 21697492 | PEPCK and G6Pase gene expressions are controlled by the transcription factor forkhead box O1 (FoxO1). |
| 2014 | 21697492 | It was unlikely that the decreased level of FoxO1 phosphorylation was mediated through Akt inactivation, as we observed an increased phosphorylation of Akt at Ser473 in HCV-infected cells compared to control cells. |
| 2015 | 21697492 | By using specific inhibitors of c-Jun N-terminal kinase (JNK) and reactive oxygen species (ROS), we demonstrated that HCV infection induced JNK activation via increased mitochondrial ROS production, resulting in decreased FoxO1 phosphorylation, FoxO1 nuclear accumulation, and, eventually, increased glucose production. |
| 2016 | 21697492 | We also found that HCV NS5A mediated increased ROS production and JNK activation, which is directly linked with the FoxO1-dependent increased gluconeogenesis. |
| 2017 | 21697492 | Here, using Huh-7.5 cells either harboring HCV-1b RNA replicons or infected with HCV-2a, we showed that HCV transcriptionally upregulated the genes for phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase), the rate-limiting enzymes for hepatic gluconeogenesis. |
| 2018 | 21697492 | PEPCK and G6Pase gene expressions are controlled by the transcription factor forkhead box O1 (FoxO1). |
| 2019 | 21697492 | It was unlikely that the decreased level of FoxO1 phosphorylation was mediated through Akt inactivation, as we observed an increased phosphorylation of Akt at Ser473 in HCV-infected cells compared to control cells. |
| 2020 | 21697492 | By using specific inhibitors of c-Jun N-terminal kinase (JNK) and reactive oxygen species (ROS), we demonstrated that HCV infection induced JNK activation via increased mitochondrial ROS production, resulting in decreased FoxO1 phosphorylation, FoxO1 nuclear accumulation, and, eventually, increased glucose production. |
| 2021 | 21697492 | We also found that HCV NS5A mediated increased ROS production and JNK activation, which is directly linked with the FoxO1-dependent increased gluconeogenesis. |
| 2022 | 21697492 | Here, using Huh-7.5 cells either harboring HCV-1b RNA replicons or infected with HCV-2a, we showed that HCV transcriptionally upregulated the genes for phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase), the rate-limiting enzymes for hepatic gluconeogenesis. |
| 2023 | 21697492 | PEPCK and G6Pase gene expressions are controlled by the transcription factor forkhead box O1 (FoxO1). |
| 2024 | 21697492 | It was unlikely that the decreased level of FoxO1 phosphorylation was mediated through Akt inactivation, as we observed an increased phosphorylation of Akt at Ser473 in HCV-infected cells compared to control cells. |
| 2025 | 21697492 | By using specific inhibitors of c-Jun N-terminal kinase (JNK) and reactive oxygen species (ROS), we demonstrated that HCV infection induced JNK activation via increased mitochondrial ROS production, resulting in decreased FoxO1 phosphorylation, FoxO1 nuclear accumulation, and, eventually, increased glucose production. |
| 2026 | 21697492 | We also found that HCV NS5A mediated increased ROS production and JNK activation, which is directly linked with the FoxO1-dependent increased gluconeogenesis. |
| 2027 | 21768169 | Potential role of estradiol and progesterone in insulin resistance through constitutive androstane receptor. |
| 2028 | 21768169 | The constitutive androstane receptor (CAR) may participate in insulin resistance in pregnancy, and sex steroids, estradiol (E(2)) and progesterone, may also be involved. |
| 2029 | 21768169 | DNA affinity immunoblotting and chromatin immunoprecipitation assay revealed that CAR ligand enhanced the recruitment of the gluconeogenic transcription factors, forkhead box O1 (FOXO1) and hepatocyte nuclear factor 4α (HNF4α), but sex steroids suppressed these recruitments on the CAR responsive element. |
| 2030 | 21804540 | Combined haploinsufficiency of FoxO1 and Notch1 markedly raises insulin sensitivity in diet-induced insulin resistance, as does liver-specific knockout of the Notch transcriptional effector Rbp-Jκ. |
| 2031 | 21804540 | Conversely, Notch1 gain-of-function promotes insulin resistance in a FoxO1-dependent manner and induces glucose-6-phosphatase expression. |
| 2032 | 21938726 | Endurance exercise training increases APPL1 expression and improves insulin signaling in the hepatic tissue of diet-induced obese mice, independently of weight loss. |
| 2033 | 21938726 | The protein kinase Akt plays a central role in the suppression of gluconeogenesis involving forkhead box O1 (Foxo1) and peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α), and in the control of glycogen synthesis involving the glycogen synthase kinase beta (GSK3β) in the liver. |
| 2034 | 21938726 | It has been demonstrated that endosomal adaptor protein APPL1 interacts with Akt and blocks the association of Akt with its endogenous inhibitor, tribbles-related protein 3 (TRB3), improving the action of insulin in the liver. |
| 2035 | 21938726 | Here, we demonstrated that chronic exercise increased the basal levels and insulin-induced Akt serine phosphorylation in the liver of diet-induced obese mice. |
| 2036 | 21938726 | Endurance training was able to increase APPL1 expression and the interaction between APPL1 and Akt. |
| 2037 | 21938726 | Conversely, training reduced both TRB3 expression and TRB3 and Akt association. |
| 2038 | 21938726 | The positive effects of exercise on insulin action are reinforced by our findings that showed that trained mice presented an increase in Foxo1 phosphorylation and Foxo1/PGC-1α association, which was accompanied by a reduction in gluconeogenic gene expressions (PEPCK and G6Pase). |
| 2039 | 21938726 | Our findings demonstrate that exercise increases insulin action, at least in part, through the enhancement of APPL1 and the reduction of TRB3 expression in the liver of obese mice, independently of weight loss. |
| 2040 | 21938726 | Endurance exercise training increases APPL1 expression and improves insulin signaling in the hepatic tissue of diet-induced obese mice, independently of weight loss. |
| 2041 | 21938726 | The protein kinase Akt plays a central role in the suppression of gluconeogenesis involving forkhead box O1 (Foxo1) and peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α), and in the control of glycogen synthesis involving the glycogen synthase kinase beta (GSK3β) in the liver. |
| 2042 | 21938726 | It has been demonstrated that endosomal adaptor protein APPL1 interacts with Akt and blocks the association of Akt with its endogenous inhibitor, tribbles-related protein 3 (TRB3), improving the action of insulin in the liver. |
| 2043 | 21938726 | Here, we demonstrated that chronic exercise increased the basal levels and insulin-induced Akt serine phosphorylation in the liver of diet-induced obese mice. |
| 2044 | 21938726 | Endurance training was able to increase APPL1 expression and the interaction between APPL1 and Akt. |
| 2045 | 21938726 | Conversely, training reduced both TRB3 expression and TRB3 and Akt association. |
| 2046 | 21938726 | The positive effects of exercise on insulin action are reinforced by our findings that showed that trained mice presented an increase in Foxo1 phosphorylation and Foxo1/PGC-1α association, which was accompanied by a reduction in gluconeogenic gene expressions (PEPCK and G6Pase). |
| 2047 | 21938726 | Our findings demonstrate that exercise increases insulin action, at least in part, through the enhancement of APPL1 and the reduction of TRB3 expression in the liver of obese mice, independently of weight loss. |
| 2048 | 21964769 | The Akt/FoxO1/p27 pathway mediates the proliferative action of liraglutide in β cells. |
| 2049 | 21964769 | In the present study, we investigated the role of Akt/FoxO1/p27 signaling in liraglutide-induced β-cell proliferation. |
| 2050 | 21964769 | The expression of Akt/FoxO1/p27 was detected by quantitative real-time PCR and Western blotting. |
| 2051 | 21964769 | Western blot analysis revealed that the phosphorylation of Akt and FoxO1 was markedly elevated following exposure to liraglutide. |
| 2052 | 21964769 | Therefore, we conclude that liraglutide increased the β-cell mass by upregulating β-cell proliferation and that the proliferative action of liraglutide in β cells was mediated by activation of PI-3K/Akt, which resulted in inactivation of FoxO1 and decreased p27. |
| 2053 | 21964769 | The Akt/FoxO1/p27 pathway mediates the proliferative action of liraglutide in β cells. |
| 2054 | 21964769 | In the present study, we investigated the role of Akt/FoxO1/p27 signaling in liraglutide-induced β-cell proliferation. |
| 2055 | 21964769 | The expression of Akt/FoxO1/p27 was detected by quantitative real-time PCR and Western blotting. |
| 2056 | 21964769 | Western blot analysis revealed that the phosphorylation of Akt and FoxO1 was markedly elevated following exposure to liraglutide. |
| 2057 | 21964769 | Therefore, we conclude that liraglutide increased the β-cell mass by upregulating β-cell proliferation and that the proliferative action of liraglutide in β cells was mediated by activation of PI-3K/Akt, which resulted in inactivation of FoxO1 and decreased p27. |
| 2058 | 21964769 | The Akt/FoxO1/p27 pathway mediates the proliferative action of liraglutide in β cells. |
| 2059 | 21964769 | In the present study, we investigated the role of Akt/FoxO1/p27 signaling in liraglutide-induced β-cell proliferation. |
| 2060 | 21964769 | The expression of Akt/FoxO1/p27 was detected by quantitative real-time PCR and Western blotting. |
| 2061 | 21964769 | Western blot analysis revealed that the phosphorylation of Akt and FoxO1 was markedly elevated following exposure to liraglutide. |
| 2062 | 21964769 | Therefore, we conclude that liraglutide increased the β-cell mass by upregulating β-cell proliferation and that the proliferative action of liraglutide in β cells was mediated by activation of PI-3K/Akt, which resulted in inactivation of FoxO1 and decreased p27. |
| 2063 | 21964769 | The Akt/FoxO1/p27 pathway mediates the proliferative action of liraglutide in β cells. |
| 2064 | 21964769 | In the present study, we investigated the role of Akt/FoxO1/p27 signaling in liraglutide-induced β-cell proliferation. |
| 2065 | 21964769 | The expression of Akt/FoxO1/p27 was detected by quantitative real-time PCR and Western blotting. |
| 2066 | 21964769 | Western blot analysis revealed that the phosphorylation of Akt and FoxO1 was markedly elevated following exposure to liraglutide. |
| 2067 | 21964769 | Therefore, we conclude that liraglutide increased the β-cell mass by upregulating β-cell proliferation and that the proliferative action of liraglutide in β cells was mediated by activation of PI-3K/Akt, which resulted in inactivation of FoxO1 and decreased p27. |
| 2068 | 21965330 | Hepatic Sirt1 deficiency in mice impairs mTorc2/Akt signaling and results in hyperglycemia, oxidative damage, and insulin resistance. |
| 2069 | 21965330 | The protein encoded by the sirtuin 1 (Sirt1) gene, which is a mouse homolog of yeast Sir2, is implicated in the regulation of glucose metabolism and insulin sensitivity; however, the underlying mechanism remains elusive. |
| 2070 | 21965330 | Here, using mice with a liver-specific null mutation of Sirt1, we have identified a signaling pathway involving Sirt1, Rictor (a component of mTOR complex 2 [mTorc2]), Akt, and Foxo1 that regulates gluconeogenesis. |
| 2071 | 21965330 | We found that Sirt1 positively regulates transcription of the gene encoding Rictor, triggering a cascade of phosphorylation of Akt at S473 and Foxo1 at S253 and resulting in decreased transcription of the gluconeogenic genes glucose-6-phosphatase (G6pase) and phosphoenolpyruvate carboxykinase (Pepck). |
| 2072 | 21965330 | This oxidative stress disrupted mTorc2 and impaired mTorc2/Akt signaling in other insulin-sensitive organs, leading to insulin resistance that could be largely reversed with antioxidant treatment. |
| 2073 | 21965330 | These data delineate a pathway through which Sirt1 maintains insulin sensitivity and suggest that treatment with antioxidants might provide protection against progressive insulin resistance in older human populations. |
| 2074 | 22012952 | Insulin decreases myocardial adiponectin receptor 1 expression via PI3K/Akt and FoxO1 pathway. |
| 2075 | 22055502 | In contrast, mice homozygous for a constitutively deacetylated Foxo1 allele (Foxo1(KR/KR)) display a unique metabolic phenotype of impaired insulin action on hepatic glucose metabolism but decreased plasma lipid levels and low respiratory quotient that are consistent with a state of preferential lipid usage. |
| 2076 | 22055502 | Moreover, Foxo1(KR/KR) mice show a dissociation between weight gain and insulin resistance in predisposing conditions (high fat diet, diabetes, and insulin receptor mutations), possibly due to decreased cytokine production in adipose tissue. |
| 2077 | 22055502 | In contrast, mice homozygous for a constitutively deacetylated Foxo1 allele (Foxo1(KR/KR)) display a unique metabolic phenotype of impaired insulin action on hepatic glucose metabolism but decreased plasma lipid levels and low respiratory quotient that are consistent with a state of preferential lipid usage. |
| 2078 | 22055502 | Moreover, Foxo1(KR/KR) mice show a dissociation between weight gain and insulin resistance in predisposing conditions (high fat diet, diabetes, and insulin receptor mutations), possibly due to decreased cytokine production in adipose tissue. |
| 2079 | 22057897 | Insulin receptor signaling mediates APP processing and β-amyloid accumulation without altering survival in a transgenic mouse model of Alzheimer's disease. |
| 2080 | 22057897 | In brains from patients with Alzheimer's disease (AD), expression of insulin receptor (IR), insulin-like growth factor-1 receptor (IGF-1R), and insulin receptor substrate proteins is downregulated. |
| 2081 | 22057897 | A key step in the pathogenesis of AD is the accumulation of amyloid precursor protein (APP) cleavage products, β-amyloid (Aβ)(1-42) and Aβ(1-40). |
| 2082 | 22057897 | Analyzing APP C-terminal fragments (CTF) revealed decreased α-/β-CTFs in the brains of nIR(-/-)Tg2576 mice suggesting decreased APP processing. |
| 2083 | 22057897 | Cell based experiments showed that inhibition of the PI3-kinase pathway suppresses endosomal APP cleavage and decreases α- as well as β-secretase activity. |
| 2084 | 22057897 | Deletion of only one copy of the neuronal IGF-1R partially rescues the premature mortality of Tg2576 mice without altering total amyloid load. |
| 2085 | 22057897 | Analysis of Tg2576 mice expressing either a dominant negative or constitutively active form of forkhead box-O (FoxO)1 did not reveal any alteration of amyloid burden, APP processing and did not rescue premature mortality in these mice. |
| 2086 | 22057897 | But exclusively decreased IGF-1R expression reduces AD-associated mortality independent of β-amyloid accumulation and FoxO1-mediated transcription. |
| 2087 | 22087313 | Free fatty acid-induced PP2A hyperactivity selectively impairs hepatic insulin action on glucose metabolism. |
| 2088 | 22087313 | While insulin-receptor phosphorylation was unaffected, activation of Akt and inactivation of the downstream targets Glycogen synthase kinase 3α (Gsk3α and Forkhead box O1 (FoxO1) was inhibited in palmitate-exposed cells. |
| 2089 | 22087313 | Accordingly, dose-response curves for insulin-mediated suppression of the FoxO1-induced gluconeogenic genes and for de novo glucose production were right shifted, and insulin-stimulated glucose oxidation and glycogen synthesis were impaired. |
| 2090 | 22087313 | The activity of the Akt-inactivating Protein Phosphatase 2A (PP2A) was increased in the insulin-resistant cells. |
| 2091 | 22087313 | Furthermore, inhibition of PP2A by specific inhibitors increased insulin-stimulated activation of Akt and phosphorylation of FoxO1 and Gsk3α. |
| 2092 | 22087313 | Finally, PP2A mRNA levels were increased in liver, muscle and adipose tissue, while PP2A activity was increased in liver and muscle tissue in insulin-resistant ZDF rats. |
| 2093 | 22087313 | In conclusion, our findings indicate that FFAs may cause a selective impairment of insulin action upon hepatic glucose metabolism by increasing PP2A activity. |
| 2094 | 22087313 | Free fatty acid-induced PP2A hyperactivity selectively impairs hepatic insulin action on glucose metabolism. |
| 2095 | 22087313 | While insulin-receptor phosphorylation was unaffected, activation of Akt and inactivation of the downstream targets Glycogen synthase kinase 3α (Gsk3α and Forkhead box O1 (FoxO1) was inhibited in palmitate-exposed cells. |
| 2096 | 22087313 | Accordingly, dose-response curves for insulin-mediated suppression of the FoxO1-induced gluconeogenic genes and for de novo glucose production were right shifted, and insulin-stimulated glucose oxidation and glycogen synthesis were impaired. |
| 2097 | 22087313 | The activity of the Akt-inactivating Protein Phosphatase 2A (PP2A) was increased in the insulin-resistant cells. |
| 2098 | 22087313 | Furthermore, inhibition of PP2A by specific inhibitors increased insulin-stimulated activation of Akt and phosphorylation of FoxO1 and Gsk3α. |
| 2099 | 22087313 | Finally, PP2A mRNA levels were increased in liver, muscle and adipose tissue, while PP2A activity was increased in liver and muscle tissue in insulin-resistant ZDF rats. |
| 2100 | 22087313 | In conclusion, our findings indicate that FFAs may cause a selective impairment of insulin action upon hepatic glucose metabolism by increasing PP2A activity. |
| 2101 | 22087313 | Free fatty acid-induced PP2A hyperactivity selectively impairs hepatic insulin action on glucose metabolism. |
| 2102 | 22087313 | While insulin-receptor phosphorylation was unaffected, activation of Akt and inactivation of the downstream targets Glycogen synthase kinase 3α (Gsk3α and Forkhead box O1 (FoxO1) was inhibited in palmitate-exposed cells. |
| 2103 | 22087313 | Accordingly, dose-response curves for insulin-mediated suppression of the FoxO1-induced gluconeogenic genes and for de novo glucose production were right shifted, and insulin-stimulated glucose oxidation and glycogen synthesis were impaired. |
| 2104 | 22087313 | The activity of the Akt-inactivating Protein Phosphatase 2A (PP2A) was increased in the insulin-resistant cells. |
| 2105 | 22087313 | Furthermore, inhibition of PP2A by specific inhibitors increased insulin-stimulated activation of Akt and phosphorylation of FoxO1 and Gsk3α. |
| 2106 | 22087313 | Finally, PP2A mRNA levels were increased in liver, muscle and adipose tissue, while PP2A activity was increased in liver and muscle tissue in insulin-resistant ZDF rats. |
| 2107 | 22087313 | In conclusion, our findings indicate that FFAs may cause a selective impairment of insulin action upon hepatic glucose metabolism by increasing PP2A activity. |
| 2108 | 22207758 | Amplification and demultiplexing in insulin-regulated Akt protein kinase pathway in adipocytes. |
| 2109 | 22207758 | Akt plays a major role in insulin regulation of metabolism in muscle, fat, and liver. |
| 2110 | 22207758 | With robust insulin stimulation, substantial changes in Akt phosphorylation using either pharmacologic or genetic manipulations had relatively little effect on Akt activity. |
| 2111 | 22207758 | Most notably, FoxO1 phosphorylation was more sensitive to insulin and did not exhibit a change in its rate of phosphorylation between 1 and 100 nm insulin compared with other substrates (AS160, TSC2, GSK3). |
| 2112 | 22207758 | Similar differences were observed between various insulin-regulated pathways such as GLUT4 translocation and protein synthesis. |
| 2113 | 22207758 | These data indicate that Akt itself is a major amplification switch in the insulin signaling pathway and that features of the pathway enable the insulin signal to be split or demultiplexed into discrete outputs. |
| 2114 | 22210743 | Differential insulin receptor substrate-1 (IRS1)-related modulation of neuropeptide Y and proopiomelanocortin expression in nondiabetic and diabetic IRS2-/- mice. |
| 2115 | 22210743 | Insulin resistance and type 2 diabetes correlate with impaired leptin and insulin signaling. |
| 2116 | 22210743 | Our aim was to analyze how leptin and insulin signaling may differentially affect the expression of hypothalamic neuropeptides regulating food intake and hypothalamic inflammation in diabetic (D) and nondiabetic (ND) IRS2(-/-) mice. |
| 2117 | 22210743 | We analyzed the activation of leptin and insulin targets by Western blotting and their association by immunoprecipitation, as well as the mRNA levels of neuropeptide Y (NPY), proopiomelanocortin, and inflammatory markers by real-time PCR and colocalization of forkhead box protein O1 (FOXO1) and NPY by double immunohistochemistry in the hypothalamus. |
| 2118 | 22210743 | Serum leptin and insulin levels and hypothalamic Janus kinase 2 and signal transducer and activator of transcription factor 3 activation were increased in ND IRS2(-/-) mice. |
| 2119 | 22210743 | IRS1 levels and its association with Janus kinase 2 and p85 and protein kinase B activation were increased in ND IRS2(-/-). |
| 2120 | 22210743 | Increased FOXO1 positively correlated with NPY mRNA levels in D IRS2(-/-) mice, with FOXO1 showing mainly nuclear localization in D IRS2(-/-) and cytoplasmic in ND IRS2(-/-) mice. |
| 2121 | 22210743 | In conclusion, differential activation of these pathways and changes in the expression of NPY and inflammation may exert a protective effect against hypothalamic deregulation of appetite, suggesting that manipulation of these targets could be of interest in the treatment of insulin resistance and type 2 diabetes. |
| 2122 | 22210743 | Differential insulin receptor substrate-1 (IRS1)-related modulation of neuropeptide Y and proopiomelanocortin expression in nondiabetic and diabetic IRS2-/- mice. |
| 2123 | 22210743 | Insulin resistance and type 2 diabetes correlate with impaired leptin and insulin signaling. |
| 2124 | 22210743 | Our aim was to analyze how leptin and insulin signaling may differentially affect the expression of hypothalamic neuropeptides regulating food intake and hypothalamic inflammation in diabetic (D) and nondiabetic (ND) IRS2(-/-) mice. |
| 2125 | 22210743 | We analyzed the activation of leptin and insulin targets by Western blotting and their association by immunoprecipitation, as well as the mRNA levels of neuropeptide Y (NPY), proopiomelanocortin, and inflammatory markers by real-time PCR and colocalization of forkhead box protein O1 (FOXO1) and NPY by double immunohistochemistry in the hypothalamus. |
| 2126 | 22210743 | Serum leptin and insulin levels and hypothalamic Janus kinase 2 and signal transducer and activator of transcription factor 3 activation were increased in ND IRS2(-/-) mice. |
| 2127 | 22210743 | IRS1 levels and its association with Janus kinase 2 and p85 and protein kinase B activation were increased in ND IRS2(-/-). |
| 2128 | 22210743 | Increased FOXO1 positively correlated with NPY mRNA levels in D IRS2(-/-) mice, with FOXO1 showing mainly nuclear localization in D IRS2(-/-) and cytoplasmic in ND IRS2(-/-) mice. |
| 2129 | 22210743 | In conclusion, differential activation of these pathways and changes in the expression of NPY and inflammation may exert a protective effect against hypothalamic deregulation of appetite, suggesting that manipulation of these targets could be of interest in the treatment of insulin resistance and type 2 diabetes. |
| 2130 | 22215655 | We previously reported that forkhead box O1 (FoxO1) inhibits β-cell growth through a Pdx1-mediated mechanism. |
| 2131 | 22215655 | However, we also reported that FoxO1 protects against β-cell failure via the induction of NeuroD and MafA. |
| 2132 | 22215655 | Here, we investigate the physiological roles of FoxO1 in the pancreas by generating the mice with deletion of FoxO1 in the domains of the Pdx1 promoter (P-FoxO1-KO) or the insulin 2 promoter (β-FoxO1-KO) and analyzing the metabolic parameters and pancreatic morphology under two different conditions of increased metabolic demand: high-fat high-sucrose diet (HFHSD) and db/db background. |
| 2133 | 22215655 | Electron microscope analysis revealed fewer insulin granules in FoxO1 knockout db/db mice. |
| 2134 | 22215655 | We conclude that FoxO1 functions as a double-edged sword in the pancreas; FoxO1 essentially inhibits β-cell neogenesis from pancreatic duct cells but is required for the maintenance of insulin secretion under metabolic stress. |
| 2135 | 22215655 | We previously reported that forkhead box O1 (FoxO1) inhibits β-cell growth through a Pdx1-mediated mechanism. |
| 2136 | 22215655 | However, we also reported that FoxO1 protects against β-cell failure via the induction of NeuroD and MafA. |
| 2137 | 22215655 | Here, we investigate the physiological roles of FoxO1 in the pancreas by generating the mice with deletion of FoxO1 in the domains of the Pdx1 promoter (P-FoxO1-KO) or the insulin 2 promoter (β-FoxO1-KO) and analyzing the metabolic parameters and pancreatic morphology under two different conditions of increased metabolic demand: high-fat high-sucrose diet (HFHSD) and db/db background. |
| 2138 | 22215655 | Electron microscope analysis revealed fewer insulin granules in FoxO1 knockout db/db mice. |
| 2139 | 22215655 | We conclude that FoxO1 functions as a double-edged sword in the pancreas; FoxO1 essentially inhibits β-cell neogenesis from pancreatic duct cells but is required for the maintenance of insulin secretion under metabolic stress. |
| 2140 | 22215655 | We previously reported that forkhead box O1 (FoxO1) inhibits β-cell growth through a Pdx1-mediated mechanism. |
| 2141 | 22215655 | However, we also reported that FoxO1 protects against β-cell failure via the induction of NeuroD and MafA. |
| 2142 | 22215655 | Here, we investigate the physiological roles of FoxO1 in the pancreas by generating the mice with deletion of FoxO1 in the domains of the Pdx1 promoter (P-FoxO1-KO) or the insulin 2 promoter (β-FoxO1-KO) and analyzing the metabolic parameters and pancreatic morphology under two different conditions of increased metabolic demand: high-fat high-sucrose diet (HFHSD) and db/db background. |
| 2143 | 22215655 | Electron microscope analysis revealed fewer insulin granules in FoxO1 knockout db/db mice. |
| 2144 | 22215655 | We conclude that FoxO1 functions as a double-edged sword in the pancreas; FoxO1 essentially inhibits β-cell neogenesis from pancreatic duct cells but is required for the maintenance of insulin secretion under metabolic stress. |
| 2145 | 22215655 | We previously reported that forkhead box O1 (FoxO1) inhibits β-cell growth through a Pdx1-mediated mechanism. |
| 2146 | 22215655 | However, we also reported that FoxO1 protects against β-cell failure via the induction of NeuroD and MafA. |
| 2147 | 22215655 | Here, we investigate the physiological roles of FoxO1 in the pancreas by generating the mice with deletion of FoxO1 in the domains of the Pdx1 promoter (P-FoxO1-KO) or the insulin 2 promoter (β-FoxO1-KO) and analyzing the metabolic parameters and pancreatic morphology under two different conditions of increased metabolic demand: high-fat high-sucrose diet (HFHSD) and db/db background. |
| 2148 | 22215655 | Electron microscope analysis revealed fewer insulin granules in FoxO1 knockout db/db mice. |
| 2149 | 22215655 | We conclude that FoxO1 functions as a double-edged sword in the pancreas; FoxO1 essentially inhibits β-cell neogenesis from pancreatic duct cells but is required for the maintenance of insulin secretion under metabolic stress. |
| 2150 | 22215655 | We previously reported that forkhead box O1 (FoxO1) inhibits β-cell growth through a Pdx1-mediated mechanism. |
| 2151 | 22215655 | However, we also reported that FoxO1 protects against β-cell failure via the induction of NeuroD and MafA. |
| 2152 | 22215655 | Here, we investigate the physiological roles of FoxO1 in the pancreas by generating the mice with deletion of FoxO1 in the domains of the Pdx1 promoter (P-FoxO1-KO) or the insulin 2 promoter (β-FoxO1-KO) and analyzing the metabolic parameters and pancreatic morphology under two different conditions of increased metabolic demand: high-fat high-sucrose diet (HFHSD) and db/db background. |
| 2153 | 22215655 | Electron microscope analysis revealed fewer insulin granules in FoxO1 knockout db/db mice. |
| 2154 | 22215655 | We conclude that FoxO1 functions as a double-edged sword in the pancreas; FoxO1 essentially inhibits β-cell neogenesis from pancreatic duct cells but is required for the maintenance of insulin secretion under metabolic stress. |
| 2155 | 22291689 | HCV infection transcriptionally up-regulated the genes for phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase), the rate-limiting enzymes for hepatic gluconeogenesis. |
| 2156 | 22291689 | Gene expression of PEPCK and G6Pase was regulated by the transcription factor forkhead box O1 (FoxO1) in HCV-infected cells. |
| 2157 | 22319636 | InsR/FoxO1 signaling curtails hypothalamic POMC neuron number. |
| 2158 | 22319636 | To investigate the role of InsR/FoxO1 signaling in the development and maintenance of these circuits, we surveyed the pool of hypothalamic neurons expressing Pomc mRNA in different mouse models of impaired hypothalamic InsR signaling. |
| 2159 | 22319636 | To establish whether FoxO1 signaling plays a role in this process, we examined POMC neuron number in mice with POMC-specific deletion of FoxO1, and detected a 23% decrease in age-matched animals, consistent with a cell-autonomous role of InsR/FoxO1 signaling in regulating POMC neuron number, distinct from its established role to activate Pomc transcription. |
| 2160 | 22319636 | InsR/FoxO1 signaling curtails hypothalamic POMC neuron number. |
| 2161 | 22319636 | To investigate the role of InsR/FoxO1 signaling in the development and maintenance of these circuits, we surveyed the pool of hypothalamic neurons expressing Pomc mRNA in different mouse models of impaired hypothalamic InsR signaling. |
| 2162 | 22319636 | To establish whether FoxO1 signaling plays a role in this process, we examined POMC neuron number in mice with POMC-specific deletion of FoxO1, and detected a 23% decrease in age-matched animals, consistent with a cell-autonomous role of InsR/FoxO1 signaling in regulating POMC neuron number, distinct from its established role to activate Pomc transcription. |
| 2163 | 22319636 | InsR/FoxO1 signaling curtails hypothalamic POMC neuron number. |
| 2164 | 22319636 | To investigate the role of InsR/FoxO1 signaling in the development and maintenance of these circuits, we surveyed the pool of hypothalamic neurons expressing Pomc mRNA in different mouse models of impaired hypothalamic InsR signaling. |
| 2165 | 22319636 | To establish whether FoxO1 signaling plays a role in this process, we examined POMC neuron number in mice with POMC-specific deletion of FoxO1, and detected a 23% decrease in age-matched animals, consistent with a cell-autonomous role of InsR/FoxO1 signaling in regulating POMC neuron number, distinct from its established role to activate Pomc transcription. |
| 2166 | 22344295 | Insulin regulates liver metabolism in vivo in the absence of hepatic Akt and Foxo1. |
| 2167 | 22344295 | Considerable data support the idea that forkhead box O1 (Foxo1) drives the liver transcriptional program during fasting and is then inhibited by thymoma viral proto-oncogene 1 (Akt) after feeding. |
| 2168 | 22344295 | Here we show that mice with hepatic deletion of Akt1 and Akt2 were glucose intolerant, insulin resistant and defective in their transcriptional response to feeding in the liver. |
| 2169 | 22344295 | Notably, in the absence of both Akt and Foxo1, mice adapted appropriately to both the fasted and fed state, and insulin suppressed hepatic glucose production normally. |
| 2170 | 22344295 | A gene expression analysis revealed that deletion of Akt in liver led to the constitutive activation of Foxo1-dependent gene expression, but again, concomitant ablation of Foxo1 restored postprandial regulation, preventing the inhibition of the metabolic response to nutrient intake caused by deletion of Akt. |
| 2171 | 22344295 | These results are inconsistent with the canonical model of hepatic metabolism in which Akt is an obligate intermediate for proper insulin signaling. |
| 2172 | 22344295 | Rather, they show that a major role of hepatic Akt is to restrain the activity of Foxo1 and that in the absence of Foxo1, Akt is largely dispensable for insulin- and nutrient-mediated hepatic metabolic regulation in vivo. |
| 2173 | 22344295 | Insulin regulates liver metabolism in vivo in the absence of hepatic Akt and Foxo1. |
| 2174 | 22344295 | Considerable data support the idea that forkhead box O1 (Foxo1) drives the liver transcriptional program during fasting and is then inhibited by thymoma viral proto-oncogene 1 (Akt) after feeding. |
| 2175 | 22344295 | Here we show that mice with hepatic deletion of Akt1 and Akt2 were glucose intolerant, insulin resistant and defective in their transcriptional response to feeding in the liver. |
| 2176 | 22344295 | Notably, in the absence of both Akt and Foxo1, mice adapted appropriately to both the fasted and fed state, and insulin suppressed hepatic glucose production normally. |
| 2177 | 22344295 | A gene expression analysis revealed that deletion of Akt in liver led to the constitutive activation of Foxo1-dependent gene expression, but again, concomitant ablation of Foxo1 restored postprandial regulation, preventing the inhibition of the metabolic response to nutrient intake caused by deletion of Akt. |
| 2178 | 22344295 | These results are inconsistent with the canonical model of hepatic metabolism in which Akt is an obligate intermediate for proper insulin signaling. |
| 2179 | 22344295 | Rather, they show that a major role of hepatic Akt is to restrain the activity of Foxo1 and that in the absence of Foxo1, Akt is largely dispensable for insulin- and nutrient-mediated hepatic metabolic regulation in vivo. |
| 2180 | 22344295 | Insulin regulates liver metabolism in vivo in the absence of hepatic Akt and Foxo1. |
| 2181 | 22344295 | Considerable data support the idea that forkhead box O1 (Foxo1) drives the liver transcriptional program during fasting and is then inhibited by thymoma viral proto-oncogene 1 (Akt) after feeding. |
| 2182 | 22344295 | Here we show that mice with hepatic deletion of Akt1 and Akt2 were glucose intolerant, insulin resistant and defective in their transcriptional response to feeding in the liver. |
| 2183 | 22344295 | Notably, in the absence of both Akt and Foxo1, mice adapted appropriately to both the fasted and fed state, and insulin suppressed hepatic glucose production normally. |
| 2184 | 22344295 | A gene expression analysis revealed that deletion of Akt in liver led to the constitutive activation of Foxo1-dependent gene expression, but again, concomitant ablation of Foxo1 restored postprandial regulation, preventing the inhibition of the metabolic response to nutrient intake caused by deletion of Akt. |
| 2185 | 22344295 | These results are inconsistent with the canonical model of hepatic metabolism in which Akt is an obligate intermediate for proper insulin signaling. |
| 2186 | 22344295 | Rather, they show that a major role of hepatic Akt is to restrain the activity of Foxo1 and that in the absence of Foxo1, Akt is largely dispensable for insulin- and nutrient-mediated hepatic metabolic regulation in vivo. |
| 2187 | 22344295 | Insulin regulates liver metabolism in vivo in the absence of hepatic Akt and Foxo1. |
| 2188 | 22344295 | Considerable data support the idea that forkhead box O1 (Foxo1) drives the liver transcriptional program during fasting and is then inhibited by thymoma viral proto-oncogene 1 (Akt) after feeding. |
| 2189 | 22344295 | Here we show that mice with hepatic deletion of Akt1 and Akt2 were glucose intolerant, insulin resistant and defective in their transcriptional response to feeding in the liver. |
| 2190 | 22344295 | Notably, in the absence of both Akt and Foxo1, mice adapted appropriately to both the fasted and fed state, and insulin suppressed hepatic glucose production normally. |
| 2191 | 22344295 | A gene expression analysis revealed that deletion of Akt in liver led to the constitutive activation of Foxo1-dependent gene expression, but again, concomitant ablation of Foxo1 restored postprandial regulation, preventing the inhibition of the metabolic response to nutrient intake caused by deletion of Akt. |
| 2192 | 22344295 | These results are inconsistent with the canonical model of hepatic metabolism in which Akt is an obligate intermediate for proper insulin signaling. |
| 2193 | 22344295 | Rather, they show that a major role of hepatic Akt is to restrain the activity of Foxo1 and that in the absence of Foxo1, Akt is largely dispensable for insulin- and nutrient-mediated hepatic metabolic regulation in vivo. |
| 2194 | 22344295 | Insulin regulates liver metabolism in vivo in the absence of hepatic Akt and Foxo1. |
| 2195 | 22344295 | Considerable data support the idea that forkhead box O1 (Foxo1) drives the liver transcriptional program during fasting and is then inhibited by thymoma viral proto-oncogene 1 (Akt) after feeding. |
| 2196 | 22344295 | Here we show that mice with hepatic deletion of Akt1 and Akt2 were glucose intolerant, insulin resistant and defective in their transcriptional response to feeding in the liver. |
| 2197 | 22344295 | Notably, in the absence of both Akt and Foxo1, mice adapted appropriately to both the fasted and fed state, and insulin suppressed hepatic glucose production normally. |
| 2198 | 22344295 | A gene expression analysis revealed that deletion of Akt in liver led to the constitutive activation of Foxo1-dependent gene expression, but again, concomitant ablation of Foxo1 restored postprandial regulation, preventing the inhibition of the metabolic response to nutrient intake caused by deletion of Akt. |
| 2199 | 22344295 | These results are inconsistent with the canonical model of hepatic metabolism in which Akt is an obligate intermediate for proper insulin signaling. |
| 2200 | 22344295 | Rather, they show that a major role of hepatic Akt is to restrain the activity of Foxo1 and that in the absence of Foxo1, Akt is largely dispensable for insulin- and nutrient-mediated hepatic metabolic regulation in vivo. |
| 2201 | 22389493 | Surprisingly, we report here that when Foxo1(KR/KR) mice are intercrossed with low density lipoprotein receptor knock-out mice (Ldlr(-/-)), they develop larger aortic root atherosclerotic lesions than Ldlr(-/-) controls despite lower plasma cholesterol and triglyceride levels. |
| 2202 | 22389493 | The phenotype is unaffected by transplanting bone marrow from Ldlr(-/-) mice into Foxo1(KR/KR) mice, indicating that it is independent of hematopoietic cells and suggesting that the primary lesion in Foxo1(KR/KR) mice occurs in the vessel wall. |
| 2203 | 22389493 | Experiments in isolated endothelial cells from Foxo1(KR/KR) mice indicate that deacetylation favors FoxO1 nuclear accumulation and exerts target gene-specific effects, resulting in higher Icam1 and Tnfα expression and increased monocyte adhesion. |
| 2204 | 22389493 | Surprisingly, we report here that when Foxo1(KR/KR) mice are intercrossed with low density lipoprotein receptor knock-out mice (Ldlr(-/-)), they develop larger aortic root atherosclerotic lesions than Ldlr(-/-) controls despite lower plasma cholesterol and triglyceride levels. |
| 2205 | 22389493 | The phenotype is unaffected by transplanting bone marrow from Ldlr(-/-) mice into Foxo1(KR/KR) mice, indicating that it is independent of hematopoietic cells and suggesting that the primary lesion in Foxo1(KR/KR) mice occurs in the vessel wall. |
| 2206 | 22389493 | Experiments in isolated endothelial cells from Foxo1(KR/KR) mice indicate that deacetylation favors FoxO1 nuclear accumulation and exerts target gene-specific effects, resulting in higher Icam1 and Tnfα expression and increased monocyte adhesion. |
| 2207 | 22389493 | Surprisingly, we report here that when Foxo1(KR/KR) mice are intercrossed with low density lipoprotein receptor knock-out mice (Ldlr(-/-)), they develop larger aortic root atherosclerotic lesions than Ldlr(-/-) controls despite lower plasma cholesterol and triglyceride levels. |
| 2208 | 22389493 | The phenotype is unaffected by transplanting bone marrow from Ldlr(-/-) mice into Foxo1(KR/KR) mice, indicating that it is independent of hematopoietic cells and suggesting that the primary lesion in Foxo1(KR/KR) mice occurs in the vessel wall. |
| 2209 | 22389493 | Experiments in isolated endothelial cells from Foxo1(KR/KR) mice indicate that deacetylation favors FoxO1 nuclear accumulation and exerts target gene-specific effects, resulting in higher Icam1 and Tnfα expression and increased monocyte adhesion. |
| 2210 | 22454632 | The FOXO family of forkhead transcription factors including FOXO1, FOXO3, FOXO4, and FOXO6 play important roles in the regulation of many cellular and biological processes and are critical regulators of cellular oxidative stress response pathways. |
| 2211 | 22456735 | Gut insulin from Foxo1 loss. |
| 2212 | 22489460 | [Hepatitis C virus core protein upregulates the transcription of PCK1 through FOXO1/PGC-1alpha pathway]. |
| 2213 | 22529213 | Mild endoplasmic reticulum stress augments the proinflammatory effect of IL-1β in pancreatic rat β-cells via the IRE1α/XBP1s pathway. |
| 2214 | 22529213 | CPA pretreatment enhanced IL-1β- induced, but not TNF-α-induced, expression of chemokine (C-C motif) ligand 2, chemokine (C-X-C motif) ligand 1, inducible nitric oxide synthase, and Fas via augmented nuclear factor κB (NF-κB) activation. |
| 2215 | 22529213 | X-box binding protein 1 (XBP1) and inositol-requiring enzyme 1, but not CCAAT/enhancer binding protein homologous protein, knockdown prevented the CPA-induced exacerbation of NF-κB-dependent genes and decreased IL-1β-induced NF-κB promoter activity. |
| 2216 | 22529213 | XBP1 modulated NF-κB activity via forkhead box O1 inhibition. |
| 2217 | 22529213 | In conclusion, rat β-cells facing mild ER stress are sensitized to IL-1β, generating a more intense and protracted inflammatory response through inositol-requiring enzyme 1/XBP1 activation. |
| 2218 | 22564731 | SIRT1 attenuates palmitate-induced endoplasmic reticulum stress and insulin resistance in HepG2 cells via induction of oxygen-regulated protein 150. |
| 2219 | 22564731 | Although SIRT1 has a therapeutic effect on T2DM, the mechanisms by which SIRT1 ameliorates insulin resistance (IR) remain unclear. |
| 2220 | 22564731 | Treatment with resveratrol, a SIRT1 activator significantly inhibited palmitate-induced ER stress, leading to the protection against palmitate-induced ER stress and insulin resistance. |
| 2221 | 22564731 | Resveratrol and SIRT1 overexpression induced the expression of oxygen-regulated protein (ORP) 150 in HepG2 cells. |
| 2222 | 22564731 | Forkhead box O1 (FOXO1) was involved in the regulation of ORP150 expression because suppression of FOXO1 inhibited the induction of ORP150 by SIRT1. |
| 2223 | 22564731 | Our results indicate a novel mechanism by which SIRT1 regulates ER stress by overexpression of ORP150, and suggest that SIRT1 ameliorates palmitate-induced insulin resistance in HepG2 cells via regulation of ER stress. |
| 2224 | 22570335 | FOXO1 mediates the autocrine effect of endothelin-1 on endothelial cell survival. |
| 2225 | 22570335 | To understand the underlying mechanism, we studied the effect of endothelin-1 (ET-1) on endothelial production of Forkhead box O1 (FOXO1), a forkhead transcription factor that plays an important role in cell survival. |
| 2226 | 22570335 | FOXO1 was shown to stimulate B cell leukemia/lymphoma 2-associated death promoter (BAD) production and promote cellular apoptosis. |
| 2227 | 22570335 | In response to ET-1, FOXO1 was phosphorylated and translocated from the nucleus to cytoplasm, resulting in inhibition of BAD production and mitigation of FOXO1-mediated apoptosis. |
| 2228 | 22570335 | This effect accounted for unbridled FOXO1 activity in the nucleus, contributing to augmented BAD production and endothelial apoptosis under hyperglycemic conditions. |
| 2229 | 22570335 | This hyperglycemia-elicited FOXO1 deregulation and its ensuing effect on endothelial cell survival was corrected by ET-1. |
| 2230 | 22570335 | Likewise, FoxO1 deregulation in the aorta of diabetic mice was reversible after the reduction of hyperglycemia by insulin therapy. |
| 2231 | 22570335 | These data reveal a mechanism by which FOXO1 mediated the autocrine effect of ET-1 on endothelial cell survival. |
| 2232 | 22570335 | FOXO1 deregulation, resulting from an impaired ability of ET-1 to control FOXO1 activity in endothelium, may contribute to hyperglycemia-induced endothelial lesion in diabetes. |
| 2233 | 22570335 | FOXO1 mediates the autocrine effect of endothelin-1 on endothelial cell survival. |
| 2234 | 22570335 | To understand the underlying mechanism, we studied the effect of endothelin-1 (ET-1) on endothelial production of Forkhead box O1 (FOXO1), a forkhead transcription factor that plays an important role in cell survival. |
| 2235 | 22570335 | FOXO1 was shown to stimulate B cell leukemia/lymphoma 2-associated death promoter (BAD) production and promote cellular apoptosis. |
| 2236 | 22570335 | In response to ET-1, FOXO1 was phosphorylated and translocated from the nucleus to cytoplasm, resulting in inhibition of BAD production and mitigation of FOXO1-mediated apoptosis. |
| 2237 | 22570335 | This effect accounted for unbridled FOXO1 activity in the nucleus, contributing to augmented BAD production and endothelial apoptosis under hyperglycemic conditions. |
| 2238 | 22570335 | This hyperglycemia-elicited FOXO1 deregulation and its ensuing effect on endothelial cell survival was corrected by ET-1. |
| 2239 | 22570335 | Likewise, FoxO1 deregulation in the aorta of diabetic mice was reversible after the reduction of hyperglycemia by insulin therapy. |
| 2240 | 22570335 | These data reveal a mechanism by which FOXO1 mediated the autocrine effect of ET-1 on endothelial cell survival. |
| 2241 | 22570335 | FOXO1 deregulation, resulting from an impaired ability of ET-1 to control FOXO1 activity in endothelium, may contribute to hyperglycemia-induced endothelial lesion in diabetes. |
| 2242 | 22570335 | FOXO1 mediates the autocrine effect of endothelin-1 on endothelial cell survival. |
| 2243 | 22570335 | To understand the underlying mechanism, we studied the effect of endothelin-1 (ET-1) on endothelial production of Forkhead box O1 (FOXO1), a forkhead transcription factor that plays an important role in cell survival. |
| 2244 | 22570335 | FOXO1 was shown to stimulate B cell leukemia/lymphoma 2-associated death promoter (BAD) production and promote cellular apoptosis. |
| 2245 | 22570335 | In response to ET-1, FOXO1 was phosphorylated and translocated from the nucleus to cytoplasm, resulting in inhibition of BAD production and mitigation of FOXO1-mediated apoptosis. |
| 2246 | 22570335 | This effect accounted for unbridled FOXO1 activity in the nucleus, contributing to augmented BAD production and endothelial apoptosis under hyperglycemic conditions. |
| 2247 | 22570335 | This hyperglycemia-elicited FOXO1 deregulation and its ensuing effect on endothelial cell survival was corrected by ET-1. |
| 2248 | 22570335 | Likewise, FoxO1 deregulation in the aorta of diabetic mice was reversible after the reduction of hyperglycemia by insulin therapy. |
| 2249 | 22570335 | These data reveal a mechanism by which FOXO1 mediated the autocrine effect of ET-1 on endothelial cell survival. |
| 2250 | 22570335 | FOXO1 deregulation, resulting from an impaired ability of ET-1 to control FOXO1 activity in endothelium, may contribute to hyperglycemia-induced endothelial lesion in diabetes. |
| 2251 | 22570335 | FOXO1 mediates the autocrine effect of endothelin-1 on endothelial cell survival. |
| 2252 | 22570335 | To understand the underlying mechanism, we studied the effect of endothelin-1 (ET-1) on endothelial production of Forkhead box O1 (FOXO1), a forkhead transcription factor that plays an important role in cell survival. |
| 2253 | 22570335 | FOXO1 was shown to stimulate B cell leukemia/lymphoma 2-associated death promoter (BAD) production and promote cellular apoptosis. |
| 2254 | 22570335 | In response to ET-1, FOXO1 was phosphorylated and translocated from the nucleus to cytoplasm, resulting in inhibition of BAD production and mitigation of FOXO1-mediated apoptosis. |
| 2255 | 22570335 | This effect accounted for unbridled FOXO1 activity in the nucleus, contributing to augmented BAD production and endothelial apoptosis under hyperglycemic conditions. |
| 2256 | 22570335 | This hyperglycemia-elicited FOXO1 deregulation and its ensuing effect on endothelial cell survival was corrected by ET-1. |
| 2257 | 22570335 | Likewise, FoxO1 deregulation in the aorta of diabetic mice was reversible after the reduction of hyperglycemia by insulin therapy. |
| 2258 | 22570335 | These data reveal a mechanism by which FOXO1 mediated the autocrine effect of ET-1 on endothelial cell survival. |
| 2259 | 22570335 | FOXO1 deregulation, resulting from an impaired ability of ET-1 to control FOXO1 activity in endothelium, may contribute to hyperglycemia-induced endothelial lesion in diabetes. |
| 2260 | 22570335 | FOXO1 mediates the autocrine effect of endothelin-1 on endothelial cell survival. |
| 2261 | 22570335 | To understand the underlying mechanism, we studied the effect of endothelin-1 (ET-1) on endothelial production of Forkhead box O1 (FOXO1), a forkhead transcription factor that plays an important role in cell survival. |
| 2262 | 22570335 | FOXO1 was shown to stimulate B cell leukemia/lymphoma 2-associated death promoter (BAD) production and promote cellular apoptosis. |
| 2263 | 22570335 | In response to ET-1, FOXO1 was phosphorylated and translocated from the nucleus to cytoplasm, resulting in inhibition of BAD production and mitigation of FOXO1-mediated apoptosis. |
| 2264 | 22570335 | This effect accounted for unbridled FOXO1 activity in the nucleus, contributing to augmented BAD production and endothelial apoptosis under hyperglycemic conditions. |
| 2265 | 22570335 | This hyperglycemia-elicited FOXO1 deregulation and its ensuing effect on endothelial cell survival was corrected by ET-1. |
| 2266 | 22570335 | Likewise, FoxO1 deregulation in the aorta of diabetic mice was reversible after the reduction of hyperglycemia by insulin therapy. |
| 2267 | 22570335 | These data reveal a mechanism by which FOXO1 mediated the autocrine effect of ET-1 on endothelial cell survival. |
| 2268 | 22570335 | FOXO1 deregulation, resulting from an impaired ability of ET-1 to control FOXO1 activity in endothelium, may contribute to hyperglycemia-induced endothelial lesion in diabetes. |
| 2269 | 22570335 | FOXO1 mediates the autocrine effect of endothelin-1 on endothelial cell survival. |
| 2270 | 22570335 | To understand the underlying mechanism, we studied the effect of endothelin-1 (ET-1) on endothelial production of Forkhead box O1 (FOXO1), a forkhead transcription factor that plays an important role in cell survival. |
| 2271 | 22570335 | FOXO1 was shown to stimulate B cell leukemia/lymphoma 2-associated death promoter (BAD) production and promote cellular apoptosis. |
| 2272 | 22570335 | In response to ET-1, FOXO1 was phosphorylated and translocated from the nucleus to cytoplasm, resulting in inhibition of BAD production and mitigation of FOXO1-mediated apoptosis. |
| 2273 | 22570335 | This effect accounted for unbridled FOXO1 activity in the nucleus, contributing to augmented BAD production and endothelial apoptosis under hyperglycemic conditions. |
| 2274 | 22570335 | This hyperglycemia-elicited FOXO1 deregulation and its ensuing effect on endothelial cell survival was corrected by ET-1. |
| 2275 | 22570335 | Likewise, FoxO1 deregulation in the aorta of diabetic mice was reversible after the reduction of hyperglycemia by insulin therapy. |
| 2276 | 22570335 | These data reveal a mechanism by which FOXO1 mediated the autocrine effect of ET-1 on endothelial cell survival. |
| 2277 | 22570335 | FOXO1 deregulation, resulting from an impaired ability of ET-1 to control FOXO1 activity in endothelium, may contribute to hyperglycemia-induced endothelial lesion in diabetes. |
| 2278 | 22570335 | FOXO1 mediates the autocrine effect of endothelin-1 on endothelial cell survival. |
| 2279 | 22570335 | To understand the underlying mechanism, we studied the effect of endothelin-1 (ET-1) on endothelial production of Forkhead box O1 (FOXO1), a forkhead transcription factor that plays an important role in cell survival. |
| 2280 | 22570335 | FOXO1 was shown to stimulate B cell leukemia/lymphoma 2-associated death promoter (BAD) production and promote cellular apoptosis. |
| 2281 | 22570335 | In response to ET-1, FOXO1 was phosphorylated and translocated from the nucleus to cytoplasm, resulting in inhibition of BAD production and mitigation of FOXO1-mediated apoptosis. |
| 2282 | 22570335 | This effect accounted for unbridled FOXO1 activity in the nucleus, contributing to augmented BAD production and endothelial apoptosis under hyperglycemic conditions. |
| 2283 | 22570335 | This hyperglycemia-elicited FOXO1 deregulation and its ensuing effect on endothelial cell survival was corrected by ET-1. |
| 2284 | 22570335 | Likewise, FoxO1 deregulation in the aorta of diabetic mice was reversible after the reduction of hyperglycemia by insulin therapy. |
| 2285 | 22570335 | These data reveal a mechanism by which FOXO1 mediated the autocrine effect of ET-1 on endothelial cell survival. |
| 2286 | 22570335 | FOXO1 deregulation, resulting from an impaired ability of ET-1 to control FOXO1 activity in endothelium, may contribute to hyperglycemia-induced endothelial lesion in diabetes. |
| 2287 | 22570335 | FOXO1 mediates the autocrine effect of endothelin-1 on endothelial cell survival. |
| 2288 | 22570335 | To understand the underlying mechanism, we studied the effect of endothelin-1 (ET-1) on endothelial production of Forkhead box O1 (FOXO1), a forkhead transcription factor that plays an important role in cell survival. |
| 2289 | 22570335 | FOXO1 was shown to stimulate B cell leukemia/lymphoma 2-associated death promoter (BAD) production and promote cellular apoptosis. |
| 2290 | 22570335 | In response to ET-1, FOXO1 was phosphorylated and translocated from the nucleus to cytoplasm, resulting in inhibition of BAD production and mitigation of FOXO1-mediated apoptosis. |
| 2291 | 22570335 | This effect accounted for unbridled FOXO1 activity in the nucleus, contributing to augmented BAD production and endothelial apoptosis under hyperglycemic conditions. |
| 2292 | 22570335 | This hyperglycemia-elicited FOXO1 deregulation and its ensuing effect on endothelial cell survival was corrected by ET-1. |
| 2293 | 22570335 | Likewise, FoxO1 deregulation in the aorta of diabetic mice was reversible after the reduction of hyperglycemia by insulin therapy. |
| 2294 | 22570335 | These data reveal a mechanism by which FOXO1 mediated the autocrine effect of ET-1 on endothelial cell survival. |
| 2295 | 22570335 | FOXO1 deregulation, resulting from an impaired ability of ET-1 to control FOXO1 activity in endothelium, may contribute to hyperglycemia-induced endothelial lesion in diabetes. |
| 2296 | 22570335 | FOXO1 mediates the autocrine effect of endothelin-1 on endothelial cell survival. |
| 2297 | 22570335 | To understand the underlying mechanism, we studied the effect of endothelin-1 (ET-1) on endothelial production of Forkhead box O1 (FOXO1), a forkhead transcription factor that plays an important role in cell survival. |
| 2298 | 22570335 | FOXO1 was shown to stimulate B cell leukemia/lymphoma 2-associated death promoter (BAD) production and promote cellular apoptosis. |
| 2299 | 22570335 | In response to ET-1, FOXO1 was phosphorylated and translocated from the nucleus to cytoplasm, resulting in inhibition of BAD production and mitigation of FOXO1-mediated apoptosis. |
| 2300 | 22570335 | This effect accounted for unbridled FOXO1 activity in the nucleus, contributing to augmented BAD production and endothelial apoptosis under hyperglycemic conditions. |
| 2301 | 22570335 | This hyperglycemia-elicited FOXO1 deregulation and its ensuing effect on endothelial cell survival was corrected by ET-1. |
| 2302 | 22570335 | Likewise, FoxO1 deregulation in the aorta of diabetic mice was reversible after the reduction of hyperglycemia by insulin therapy. |
| 2303 | 22570335 | These data reveal a mechanism by which FOXO1 mediated the autocrine effect of ET-1 on endothelial cell survival. |
| 2304 | 22570335 | FOXO1 deregulation, resulting from an impaired ability of ET-1 to control FOXO1 activity in endothelium, may contribute to hyperglycemia-induced endothelial lesion in diabetes. |
| 2305 | 22586579 | The 3-phosphoinositide-dependent protein kinase 1 (Pdk1)/forkhead transcription factor (Foxo1) pathway is important in regulating glucose and energy homeostasis, but little is known about this pathway in adipose tissue macrophages (ATMs). |
| 2306 | 22586579 | To investigate this, we generated transgenic mice that carried macrophage/granulocyte-specific mutations, including a Pdk1 knockout (LysMPdk1(-/-)), a Pdk1 knockout with transactivation-defective Foxo1 (Δ256LysMPdk1(-/-)), a constitutively active nuclear (CN) Foxo1 (CNFoxo1(LysM)), or a transactivation-defective Foxo1 (Δ256Foxo1(LysM)). |
| 2307 | 22586579 | CNFoxo1(LysM) promoted transcription of the C-C motif chemokine receptor 2 (Ccr2) in ATMs and increased M1 macrophages in adipose tissue. |
| 2308 | 22586579 | Pdk1 deletion or Foxo1 activation in bone marrow-derived macrophages abolished insulin and interleukin-4 induction of genes involved in alternative macrophage activation. |
| 2309 | 22586579 | Thus, Pdk1 regulated macrophage infiltration by inhibiting Foxo1-induced Ccr2 expression. |
| 2310 | 22586579 | This shows that the macrophage Pdk1/Foxo1 pathway is important in regulating insulin sensitivity in vivo. |
| 2311 | 22586579 | The 3-phosphoinositide-dependent protein kinase 1 (Pdk1)/forkhead transcription factor (Foxo1) pathway is important in regulating glucose and energy homeostasis, but little is known about this pathway in adipose tissue macrophages (ATMs). |
| 2312 | 22586579 | To investigate this, we generated transgenic mice that carried macrophage/granulocyte-specific mutations, including a Pdk1 knockout (LysMPdk1(-/-)), a Pdk1 knockout with transactivation-defective Foxo1 (Δ256LysMPdk1(-/-)), a constitutively active nuclear (CN) Foxo1 (CNFoxo1(LysM)), or a transactivation-defective Foxo1 (Δ256Foxo1(LysM)). |
| 2313 | 22586579 | CNFoxo1(LysM) promoted transcription of the C-C motif chemokine receptor 2 (Ccr2) in ATMs and increased M1 macrophages in adipose tissue. |
| 2314 | 22586579 | Pdk1 deletion or Foxo1 activation in bone marrow-derived macrophages abolished insulin and interleukin-4 induction of genes involved in alternative macrophage activation. |
| 2315 | 22586579 | Thus, Pdk1 regulated macrophage infiltration by inhibiting Foxo1-induced Ccr2 expression. |
| 2316 | 22586579 | This shows that the macrophage Pdk1/Foxo1 pathway is important in regulating insulin sensitivity in vivo. |
| 2317 | 22586579 | The 3-phosphoinositide-dependent protein kinase 1 (Pdk1)/forkhead transcription factor (Foxo1) pathway is important in regulating glucose and energy homeostasis, but little is known about this pathway in adipose tissue macrophages (ATMs). |
| 2318 | 22586579 | To investigate this, we generated transgenic mice that carried macrophage/granulocyte-specific mutations, including a Pdk1 knockout (LysMPdk1(-/-)), a Pdk1 knockout with transactivation-defective Foxo1 (Δ256LysMPdk1(-/-)), a constitutively active nuclear (CN) Foxo1 (CNFoxo1(LysM)), or a transactivation-defective Foxo1 (Δ256Foxo1(LysM)). |
| 2319 | 22586579 | CNFoxo1(LysM) promoted transcription of the C-C motif chemokine receptor 2 (Ccr2) in ATMs and increased M1 macrophages in adipose tissue. |
| 2320 | 22586579 | Pdk1 deletion or Foxo1 activation in bone marrow-derived macrophages abolished insulin and interleukin-4 induction of genes involved in alternative macrophage activation. |
| 2321 | 22586579 | Thus, Pdk1 regulated macrophage infiltration by inhibiting Foxo1-induced Ccr2 expression. |
| 2322 | 22586579 | This shows that the macrophage Pdk1/Foxo1 pathway is important in regulating insulin sensitivity in vivo. |
| 2323 | 22586579 | The 3-phosphoinositide-dependent protein kinase 1 (Pdk1)/forkhead transcription factor (Foxo1) pathway is important in regulating glucose and energy homeostasis, but little is known about this pathway in adipose tissue macrophages (ATMs). |
| 2324 | 22586579 | To investigate this, we generated transgenic mice that carried macrophage/granulocyte-specific mutations, including a Pdk1 knockout (LysMPdk1(-/-)), a Pdk1 knockout with transactivation-defective Foxo1 (Δ256LysMPdk1(-/-)), a constitutively active nuclear (CN) Foxo1 (CNFoxo1(LysM)), or a transactivation-defective Foxo1 (Δ256Foxo1(LysM)). |
| 2325 | 22586579 | CNFoxo1(LysM) promoted transcription of the C-C motif chemokine receptor 2 (Ccr2) in ATMs and increased M1 macrophages in adipose tissue. |
| 2326 | 22586579 | Pdk1 deletion or Foxo1 activation in bone marrow-derived macrophages abolished insulin and interleukin-4 induction of genes involved in alternative macrophage activation. |
| 2327 | 22586579 | Thus, Pdk1 regulated macrophage infiltration by inhibiting Foxo1-induced Ccr2 expression. |
| 2328 | 22586579 | This shows that the macrophage Pdk1/Foxo1 pathway is important in regulating insulin sensitivity in vivo. |
| 2329 | 22645357 | Here we show that Skp2, an E3 ubiquitin ligase that affects cell cycle control and death, plays a critical role in the function of diabetogenic Tpaths and Tregs. |
| 2330 | 22645357 | Down-regulation of the cyclin-dependent kinase inhibitor p27 alone significantly attenuates the effect of Skp2 on Tpaths and reduces the suppressive function of converted Tregs; its effect is further improved with concomitant down-regulation of p21, Foxo1, and Foxo3. |
| 2331 | 22654904 | Interestingly, studies in rodents suggest that reduced insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF-1R) signaling decrease AD pathology, that is, β-amyloid toxicity. |
| 2332 | 22654904 | In the mammalian brain, there are FoxO1, FoxO3a, and FoxO6 expressed. |
| 2333 | 22654904 | Surprisingly, high-fat diet specifically reduces the expression of FoxO3a and FoxO6 suggesting that IR/IGF-1 → FoxO-mediated transcription is involved in the pathogenesis of obesity-associated cognitive impairment. |
| 2334 | 22654904 | Therefore, the function of FoxO1 and FoxO3a has been investigated in animal models of Alzheimer's disease in detail. |
| 2335 | 22654904 | Interestingly, studies in rodents suggest that reduced insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF-1R) signaling decrease AD pathology, that is, β-amyloid toxicity. |
| 2336 | 22654904 | In the mammalian brain, there are FoxO1, FoxO3a, and FoxO6 expressed. |
| 2337 | 22654904 | Surprisingly, high-fat diet specifically reduces the expression of FoxO3a and FoxO6 suggesting that IR/IGF-1 → FoxO-mediated transcription is involved in the pathogenesis of obesity-associated cognitive impairment. |
| 2338 | 22654904 | Therefore, the function of FoxO1 and FoxO3a has been investigated in animal models of Alzheimer's disease in detail. |
| 2339 | 22688333 | Intraportal delivery of insulin in a constant versus pulsatile pattern led to delayed and impaired activation of hepatic insulin receptor substrate (IRS)-1 and IRS-2 signaling, impaired activation of downstream insulin signaling effector molecules AKT and Foxo1, and decreased expression of glucokinase (Gck). |
| 2340 | 22688333 | We further established that hepatic Gck expression is decreased in the HIP rat model of T2DM, a defect that correlated with a progressive defect of pulsatile insulin secretion. |
| 2341 | 22733486 | The present study was carried out to examine whether resveratrol had protective effect on diabetic kidney by modulation of the Sirt1/FoxO1 pathway. |
| 2342 | 22733486 | Here we show that the FoxO1 activity was significantly reduced and with a concomitant decrease in the expression of FoxO1 target gene, catalase in diabetic kidney. |
| 2343 | 22733486 | The FoxO1 downregulation correlated with an increase in the generation of malondialdehyde (MDA), a decrease in the activity of SOD and an increase in the expression of collagen IV and fibronectin proteins in renal cortex of diabetic rats. |
| 2344 | 22733486 | Treatment with the sirtuin agonist resveratrol, with an increase in the expression of Sirt1, significantly increased FoxO1 activity in diabetic kidney. |
| 2345 | 22733486 | This correlated with a decrease in the generation of MDA, an increase in the activity of SOD, a partial reversal of collagen IV and fibronectin proteins levels and more improved kidney pathological and biochemical indicators changes. |
| 2346 | 22733486 | These data also suggest that modulation of the Sirt1/FoxO1 pathway may be a potentially useful therapeutic target for DN. |
| 2347 | 22733486 | The present study was carried out to examine whether resveratrol had protective effect on diabetic kidney by modulation of the Sirt1/FoxO1 pathway. |
| 2348 | 22733486 | Here we show that the FoxO1 activity was significantly reduced and with a concomitant decrease in the expression of FoxO1 target gene, catalase in diabetic kidney. |
| 2349 | 22733486 | The FoxO1 downregulation correlated with an increase in the generation of malondialdehyde (MDA), a decrease in the activity of SOD and an increase in the expression of collagen IV and fibronectin proteins in renal cortex of diabetic rats. |
| 2350 | 22733486 | Treatment with the sirtuin agonist resveratrol, with an increase in the expression of Sirt1, significantly increased FoxO1 activity in diabetic kidney. |
| 2351 | 22733486 | This correlated with a decrease in the generation of MDA, an increase in the activity of SOD, a partial reversal of collagen IV and fibronectin proteins levels and more improved kidney pathological and biochemical indicators changes. |
| 2352 | 22733486 | These data also suggest that modulation of the Sirt1/FoxO1 pathway may be a potentially useful therapeutic target for DN. |
| 2353 | 22733486 | The present study was carried out to examine whether resveratrol had protective effect on diabetic kidney by modulation of the Sirt1/FoxO1 pathway. |
| 2354 | 22733486 | Here we show that the FoxO1 activity was significantly reduced and with a concomitant decrease in the expression of FoxO1 target gene, catalase in diabetic kidney. |
| 2355 | 22733486 | The FoxO1 downregulation correlated with an increase in the generation of malondialdehyde (MDA), a decrease in the activity of SOD and an increase in the expression of collagen IV and fibronectin proteins in renal cortex of diabetic rats. |
| 2356 | 22733486 | Treatment with the sirtuin agonist resveratrol, with an increase in the expression of Sirt1, significantly increased FoxO1 activity in diabetic kidney. |
| 2357 | 22733486 | This correlated with a decrease in the generation of MDA, an increase in the activity of SOD, a partial reversal of collagen IV and fibronectin proteins levels and more improved kidney pathological and biochemical indicators changes. |
| 2358 | 22733486 | These data also suggest that modulation of the Sirt1/FoxO1 pathway may be a potentially useful therapeutic target for DN. |
| 2359 | 22733486 | The present study was carried out to examine whether resveratrol had protective effect on diabetic kidney by modulation of the Sirt1/FoxO1 pathway. |
| 2360 | 22733486 | Here we show that the FoxO1 activity was significantly reduced and with a concomitant decrease in the expression of FoxO1 target gene, catalase in diabetic kidney. |
| 2361 | 22733486 | The FoxO1 downregulation correlated with an increase in the generation of malondialdehyde (MDA), a decrease in the activity of SOD and an increase in the expression of collagen IV and fibronectin proteins in renal cortex of diabetic rats. |
| 2362 | 22733486 | Treatment with the sirtuin agonist resveratrol, with an increase in the expression of Sirt1, significantly increased FoxO1 activity in diabetic kidney. |
| 2363 | 22733486 | This correlated with a decrease in the generation of MDA, an increase in the activity of SOD, a partial reversal of collagen IV and fibronectin proteins levels and more improved kidney pathological and biochemical indicators changes. |
| 2364 | 22733486 | These data also suggest that modulation of the Sirt1/FoxO1 pathway may be a potentially useful therapeutic target for DN. |
| 2365 | 22733486 | The present study was carried out to examine whether resveratrol had protective effect on diabetic kidney by modulation of the Sirt1/FoxO1 pathway. |
| 2366 | 22733486 | Here we show that the FoxO1 activity was significantly reduced and with a concomitant decrease in the expression of FoxO1 target gene, catalase in diabetic kidney. |
| 2367 | 22733486 | The FoxO1 downregulation correlated with an increase in the generation of malondialdehyde (MDA), a decrease in the activity of SOD and an increase in the expression of collagen IV and fibronectin proteins in renal cortex of diabetic rats. |
| 2368 | 22733486 | Treatment with the sirtuin agonist resveratrol, with an increase in the expression of Sirt1, significantly increased FoxO1 activity in diabetic kidney. |
| 2369 | 22733486 | This correlated with a decrease in the generation of MDA, an increase in the activity of SOD, a partial reversal of collagen IV and fibronectin proteins levels and more improved kidney pathological and biochemical indicators changes. |
| 2370 | 22733486 | These data also suggest that modulation of the Sirt1/FoxO1 pathway may be a potentially useful therapeutic target for DN. |
| 2371 | 22819564 | Genistein accelerates refractory wound healing by suppressing superoxide and FoxO1/iNOS pathway in type 1 diabetes. |
| 2372 | 22819564 | Moreover, genistein attenuated diabetic cutaneous silent information regulator 1 and forkhead box O transcription factor 1 (FoxO1) levels and potentiated ac-FoxO1 in a dose-dependent manner. |
| 2373 | 22819564 | Genistein rescued the delayed wound healing and improved wound angiogenesis in STZ-induced type 1 diabetes in mice, at least in part, by suppression of FoxO1, iNOS activity and oxidative stress. |
| 2374 | 22819564 | Genistein accelerates refractory wound healing by suppressing superoxide and FoxO1/iNOS pathway in type 1 diabetes. |
| 2375 | 22819564 | Moreover, genistein attenuated diabetic cutaneous silent information regulator 1 and forkhead box O transcription factor 1 (FoxO1) levels and potentiated ac-FoxO1 in a dose-dependent manner. |
| 2376 | 22819564 | Genistein rescued the delayed wound healing and improved wound angiogenesis in STZ-induced type 1 diabetes in mice, at least in part, by suppression of FoxO1, iNOS activity and oxidative stress. |
| 2377 | 22819564 | Genistein accelerates refractory wound healing by suppressing superoxide and FoxO1/iNOS pathway in type 1 diabetes. |
| 2378 | 22819564 | Moreover, genistein attenuated diabetic cutaneous silent information regulator 1 and forkhead box O transcription factor 1 (FoxO1) levels and potentiated ac-FoxO1 in a dose-dependent manner. |
| 2379 | 22819564 | Genistein rescued the delayed wound healing and improved wound angiogenesis in STZ-induced type 1 diabetes in mice, at least in part, by suppression of FoxO1, iNOS activity and oxidative stress. |
| 2380 | 22819839 | Geniposide could prevent oxidative stress-induced neuron apoptosis, and improved glucose stimulated insulin secretion by activating glucagon-like peptide 1 receptor (GLP-1R) in INS-1 cells. |
| 2381 | 22819839 | Moreover, geniposide also improved the impairment of GLP-1R signaling through enhancing the phosphorylation of Akt and Foxo1, and increased the expression of PDX-1 in palmitate-treated INS-1 cells. |
| 2382 | 22848439 | Mapping MKP-3/FOXO1 interaction and evaluating the effect on gluconeogenesis. |
| 2383 | 22860063 | Oleanolic acid reduces hyperglycemia beyond treatment period with Akt/FoxO1-induced suppression of hepatic gluconeogenesis in type-2 diabetic mice. |
| 2384 | 22860063 | Finally, we analyzed key regulators of gluconeogenesis in the liver and found significant increases in the phosphorylation of both Akt and FoxO1 after treatment with OA. |
| 2385 | 22860063 | The liver appears to be a major site of action, possibly by the suppression of hepatic glucose production via the Akt/FoxO1 axis. |
| 2386 | 22860063 | Oleanolic acid reduces hyperglycemia beyond treatment period with Akt/FoxO1-induced suppression of hepatic gluconeogenesis in type-2 diabetic mice. |
| 2387 | 22860063 | Finally, we analyzed key regulators of gluconeogenesis in the liver and found significant increases in the phosphorylation of both Akt and FoxO1 after treatment with OA. |
| 2388 | 22860063 | The liver appears to be a major site of action, possibly by the suppression of hepatic glucose production via the Akt/FoxO1 axis. |
| 2389 | 22860063 | Oleanolic acid reduces hyperglycemia beyond treatment period with Akt/FoxO1-induced suppression of hepatic gluconeogenesis in type-2 diabetic mice. |
| 2390 | 22860063 | Finally, we analyzed key regulators of gluconeogenesis in the liver and found significant increases in the phosphorylation of both Akt and FoxO1 after treatment with OA. |
| 2391 | 22860063 | The liver appears to be a major site of action, possibly by the suppression of hepatic glucose production via the Akt/FoxO1 axis. |
| 2392 | 22868909 | In isolated muscle or fat cells, acute bradykinin (BK) stimulation was shown to improve insulin action and increase glucose uptake by promoting glucose transporter 4 translocation to plasma membrane. |
| 2393 | 22868909 | Increased gluconeogenesis was accompanied by increased hepatic mRNA expression of forkhead box protein O1 (FoxO1, four-fold), peroxisome proliferator-activated receptor gamma co-activator 1-alpha (seven-fold), phosphoenolpyruvate carboxykinase (PEPCK, three-fold) and glucose-6-phosphatase (eight-fold). |
| 2394 | 22868909 | Intraportal injection of BK in lean mice was able to decrease the hepatic mRNA expression of FoxO1 and PEPCK. |
| 2395 | 22868909 | In isolated muscle or fat cells, acute bradykinin (BK) stimulation was shown to improve insulin action and increase glucose uptake by promoting glucose transporter 4 translocation to plasma membrane. |
| 2396 | 22868909 | Increased gluconeogenesis was accompanied by increased hepatic mRNA expression of forkhead box protein O1 (FoxO1, four-fold), peroxisome proliferator-activated receptor gamma co-activator 1-alpha (seven-fold), phosphoenolpyruvate carboxykinase (PEPCK, three-fold) and glucose-6-phosphatase (eight-fold). |
| 2397 | 22868909 | Intraportal injection of BK in lean mice was able to decrease the hepatic mRNA expression of FoxO1 and PEPCK. |
| 2398 | 22940604 | Diabetes triggers a PARP1 mediated death pathway in the heart through participation of FoxO1. |
| 2399 | 22940604 | This was accompanied by a simultaneous increase in iNOS expression and iNOS induced protein nitrosylation of GAPDH, increased GAPDH binding to Siah1 and facilitated nuclear translocation of the complex. |
| 2400 | 22940604 | Even though caspase-3 was cleaved during diabetes, its nitrosylation modification affected its ability to inactivate PARP. |
| 2401 | 22940604 | As a result, there was PARP activation followed by nuclear compartmentalization of AIF, and increased phosphatidyl serine externalization. |
| 2402 | 22940604 | Our data suggests a role for FoxO1 mediated iNOS induced S-nitrosylation of target proteins like GAPDH and caspase-3 in initiating cardiac cell death following hyperglycemia, and could explain the impact of glycemic control in preventing cardiovascular disease in patients with diabetes. |
| 2403 | 22940604 | Diabetes triggers a PARP1 mediated death pathway in the heart through participation of FoxO1. |
| 2404 | 22940604 | This was accompanied by a simultaneous increase in iNOS expression and iNOS induced protein nitrosylation of GAPDH, increased GAPDH binding to Siah1 and facilitated nuclear translocation of the complex. |
| 2405 | 22940604 | Even though caspase-3 was cleaved during diabetes, its nitrosylation modification affected its ability to inactivate PARP. |
| 2406 | 22940604 | As a result, there was PARP activation followed by nuclear compartmentalization of AIF, and increased phosphatidyl serine externalization. |
| 2407 | 22940604 | Our data suggests a role for FoxO1 mediated iNOS induced S-nitrosylation of target proteins like GAPDH and caspase-3 in initiating cardiac cell death following hyperglycemia, and could explain the impact of glycemic control in preventing cardiovascular disease in patients with diabetes. |
| 2408 | 22941110 | We found that Rho-kinase 1 (ROCK1) regulates leptin action on body weight homeostasis by activating JAK2, an initial trigger of leptin receptor signaling. |
| 2409 | 22941110 | Leptin promoted the physical interaction of JAK2 and ROCK1, thereby increasing phosphorylation of JAK2 and downstream activation of Stat3 and FOXO1. |
| 2410 | 22941110 | Mice lacking ROCK1 in either pro-opiomelanocortin (POMC) or agouti-related protein neurons, mediators of leptin action, displayed obesity and impaired leptin sensitivity. |
| 2411 | 22941110 | Notably, ROCK1 was a specific mediator of leptin, but not insulin, regulation of POMC neuronal activity. |
| 2412 | 23028378 | TCF7L2 modulates glucose homeostasis by regulating CREB- and FoxO1-dependent transcriptional pathway in the liver. |
| 2413 | 23028378 | Expression of medium and short isoforms of TCF7L2 was greatly diminished in livers of diet-induced and genetic mouse models of insulin resistance, prompting us to delineate the functional role of these isoforms in hepatic glucose metabolism. |
| 2414 | 23028378 | Indeed, we observed a binding of TCF7L2 to promoters of gluconeogenic genes; and expression of TCF7L2 inhibited adjacent promoter occupancies of CREB, CRTC2, and FoxO1, critical transcriptional modules in hepatic gluconeogenesis, to disrupt target gene transcription. |
| 2415 | 23028378 | TCF7L2 modulates glucose homeostasis by regulating CREB- and FoxO1-dependent transcriptional pathway in the liver. |
| 2416 | 23028378 | Expression of medium and short isoforms of TCF7L2 was greatly diminished in livers of diet-induced and genetic mouse models of insulin resistance, prompting us to delineate the functional role of these isoforms in hepatic glucose metabolism. |
| 2417 | 23028378 | Indeed, we observed a binding of TCF7L2 to promoters of gluconeogenic genes; and expression of TCF7L2 inhibited adjacent promoter occupancies of CREB, CRTC2, and FoxO1, critical transcriptional modules in hepatic gluconeogenesis, to disrupt target gene transcription. |
| 2418 | 23066095 | The forkhead transcription factor FoxO1 is a critical regulator of hepatic glucose and lipid metabolism, and dysregulation of FoxO1 function has been implicated in diabetes and insulin resistance. |
| 2419 | 23066095 | Notably, deletion of FoxO1 caused a significantly reduced induction of Pck1 and Pdk4 in response to retinoids. |
| 2420 | 23066095 | As Pck1 and Pdk4 are downstream targets of retinoid signaling, these results suggest that FoxO1 plays a potential role in linking retinoid metabolism to hepatic gluconeogenesis. |
| 2421 | 23066095 | The forkhead transcription factor FoxO1 is a critical regulator of hepatic glucose and lipid metabolism, and dysregulation of FoxO1 function has been implicated in diabetes and insulin resistance. |
| 2422 | 23066095 | Notably, deletion of FoxO1 caused a significantly reduced induction of Pck1 and Pdk4 in response to retinoids. |
| 2423 | 23066095 | As Pck1 and Pdk4 are downstream targets of retinoid signaling, these results suggest that FoxO1 plays a potential role in linking retinoid metabolism to hepatic gluconeogenesis. |
| 2424 | 23066095 | The forkhead transcription factor FoxO1 is a critical regulator of hepatic glucose and lipid metabolism, and dysregulation of FoxO1 function has been implicated in diabetes and insulin resistance. |
| 2425 | 23066095 | Notably, deletion of FoxO1 caused a significantly reduced induction of Pck1 and Pdk4 in response to retinoids. |
| 2426 | 23066095 | As Pck1 and Pdk4 are downstream targets of retinoid signaling, these results suggest that FoxO1 plays a potential role in linking retinoid metabolism to hepatic gluconeogenesis. |
| 2427 | 23342163 | Relationship of such alteration with histone acetylase (HAT) p300 was examined. |
| 2428 | 23342163 | We also found that p300 and SIRT1 regulate each other in such process, as silencing one led to increase of the others' expression. |
| 2429 | 23342163 | Chemically induced increased SIRT1 activity and p300 knockdown corrected these abnormalities slowing aging-like changes. |
| 2430 | 23342163 | Data from this study demonstrated that hyperglycemia accelerates aging-like process in the vascular ECs and such process is mediated via downregulation of SIRT1, causing reduction of mitochondrial antioxidant enzyme in a p300 and FOXO1 mediated pathway. |
| 2431 | 23401241 | Loss of TIMP3 underlies diabetic nephropathy via FoxO1/STAT1 interplay. |
| 2432 | 23401241 | ADAM17 and its inhibitor TIMP3 are involved in nephropathy, but their role in diabetic kidney disease (DKD) is unclear. |
| 2433 | 23401241 | Microarray profiling uncovered a significant reduction of Foxo1 expression in diabetic Timp3(-/-) mice compared to WT, along with FoxO1 target genes involved in autophagy, while STAT1, a repressor of FoxO1 transcription, was increased. |
| 2434 | 23401241 | Re-expression of Timp3 in Timp3(-/-) mesangial cells rescued the expression of Foxo1 and its targets, and decreased STAT1 expression to control levels; abolishing STAT1 expression led to a rescue of FoxO1, evoking a role of STAT1 in linking Timp3 deficiency to FoxO1. |
| 2435 | 23401241 | Studies on kidney biopsies from patients with diabetic nephropathy confirmed a significant reduction in TIMP3, FoxO1 and FoxO1 target genes involved in autophagy compared to controls, while STAT1 expression was strongly increased. |
| 2436 | 23435785 | Regulation of forkhead box O1 (FOXO1) by protein kinase B and glucocorticoids: different mechanisms of induction of beta cell death in vitro. |
| 2437 | 23493572 | Hypothalamic ceramide levels regulated by CPT1C mediate the orexigenic effect of ghrelin. |
| 2438 | 23493572 | Recent data suggest that ghrelin exerts its orexigenic action through regulation of hypothalamic AMP-activated protein kinase pathway, leading to a decline in malonyl-CoA levels and desinhibition of carnitine palmitoyltransferase 1A (CPT1A), which increases mitochondrial fatty acid oxidation and ultimately enhances the expression of the orexigenic neuropeptides agouti-related protein (AgRP) and neuropeptide Y (NPY). |
| 2439 | 23493572 | Here, we demonstrate that the orexigenic action of ghrelin is totally blunted in CPT1C knockout (KO) mice, despite having the canonical ghrelin signaling pathway activated. |
| 2440 | 23493572 | We also demonstrate that ghrelin elicits a marked upregulation of hypothalamic C18:0 ceramide levels mediated by CPT1C. |
| 2441 | 23493572 | Notably, central inhibition of ceramide synthesis with myriocin negated the orexigenic action of ghrelin and normalized the levels of AgRP and NPY, as well as their key transcription factors phosphorylated cAMP-response element-binding protein and forkhead box O1. |
| 2442 | 23493572 | Overall, these data indicate that, in addition to formerly reported mechanisms, ghrelin also induces food intake through regulation of hypothalamic CPT1C and ceramide metabolism, a finding of potential importance for the understanding and treatment of obesity. |
| 2443 | 23533474 | Quercetin Preserves β -Cell Mass and Function in Fructose-Induced Hyperinsulinemia through Modulating Pancreatic Akt/FoxO1 Activation. |
| 2444 | 23533474 | Quercetin was confirmed to reduce serum insulin and leptin levels and blockade islet hyperplasia in fructose-fed rats. |
| 2445 | 23533474 | It also prevented fructose-induced β -cell proliferation and insulin hypersecretion in INS-1 β -cells. |
| 2446 | 23533474 | Quercetin downregulated Akt and FoxO1 phosphorylation in fructose-fed rat islets and increased the nuclear FoxO1 levels in fructose-treated INS-1 β -cells. |
| 2447 | 23533474 | The elevated Akt phosphorylation in fructose-treated INS-1 β -cells was also restored by quercetin. |
| 2448 | 23533474 | Additionally, quercetin suppressed the expression of pancreatic and duodenal homeobox 1 (Pdx1) and insulin gene (Ins1 and Ins2) in vivo and in vitro. |
| 2449 | 23533474 | In fructose-treated INS-1 β -cells, quercetin elevated the reduced janus kinase 2/signal transducers and activators of transcription 3 (Jak2/Stat3) phosphorylation and suppressed the increased suppressor of cytokine signaling 3 (Socs3) expression. |
| 2450 | 23533474 | These results demonstrate that quercetin protects β -cell mass and function under high-fructose induction through improving leptin signaling and preserving pancreatic Akt/FoxO1 activation. |
| 2451 | 23533474 | Quercetin Preserves β -Cell Mass and Function in Fructose-Induced Hyperinsulinemia through Modulating Pancreatic Akt/FoxO1 Activation. |
| 2452 | 23533474 | Quercetin was confirmed to reduce serum insulin and leptin levels and blockade islet hyperplasia in fructose-fed rats. |
| 2453 | 23533474 | It also prevented fructose-induced β -cell proliferation and insulin hypersecretion in INS-1 β -cells. |
| 2454 | 23533474 | Quercetin downregulated Akt and FoxO1 phosphorylation in fructose-fed rat islets and increased the nuclear FoxO1 levels in fructose-treated INS-1 β -cells. |
| 2455 | 23533474 | The elevated Akt phosphorylation in fructose-treated INS-1 β -cells was also restored by quercetin. |
| 2456 | 23533474 | Additionally, quercetin suppressed the expression of pancreatic and duodenal homeobox 1 (Pdx1) and insulin gene (Ins1 and Ins2) in vivo and in vitro. |
| 2457 | 23533474 | In fructose-treated INS-1 β -cells, quercetin elevated the reduced janus kinase 2/signal transducers and activators of transcription 3 (Jak2/Stat3) phosphorylation and suppressed the increased suppressor of cytokine signaling 3 (Socs3) expression. |
| 2458 | 23533474 | These results demonstrate that quercetin protects β -cell mass and function under high-fructose induction through improving leptin signaling and preserving pancreatic Akt/FoxO1 activation. |
| 2459 | 23533474 | Quercetin Preserves β -Cell Mass and Function in Fructose-Induced Hyperinsulinemia through Modulating Pancreatic Akt/FoxO1 Activation. |
| 2460 | 23533474 | Quercetin was confirmed to reduce serum insulin and leptin levels and blockade islet hyperplasia in fructose-fed rats. |
| 2461 | 23533474 | It also prevented fructose-induced β -cell proliferation and insulin hypersecretion in INS-1 β -cells. |
| 2462 | 23533474 | Quercetin downregulated Akt and FoxO1 phosphorylation in fructose-fed rat islets and increased the nuclear FoxO1 levels in fructose-treated INS-1 β -cells. |
| 2463 | 23533474 | The elevated Akt phosphorylation in fructose-treated INS-1 β -cells was also restored by quercetin. |
| 2464 | 23533474 | Additionally, quercetin suppressed the expression of pancreatic and duodenal homeobox 1 (Pdx1) and insulin gene (Ins1 and Ins2) in vivo and in vitro. |
| 2465 | 23533474 | In fructose-treated INS-1 β -cells, quercetin elevated the reduced janus kinase 2/signal transducers and activators of transcription 3 (Jak2/Stat3) phosphorylation and suppressed the increased suppressor of cytokine signaling 3 (Socs3) expression. |
| 2466 | 23533474 | These results demonstrate that quercetin protects β -cell mass and function under high-fructose induction through improving leptin signaling and preserving pancreatic Akt/FoxO1 activation. |
| 2467 | 23705021 | Nov/Ccn3, a novel transcriptional target of FoxO1, impairs pancreatic β-cell function. |
| 2468 | 23705021 | The forkhead transcription factor FoxO1 is a prominent mediator of insulin signaling in β-cells. |
| 2469 | 23705021 | We reasoned that identification of FoxO1 target genes in β-cells could reveal mechanisms linking β-cell dysfunction to insulin resistance. |
| 2470 | 23705021 | In this study, we report the characterization of Nov/Ccn3 as a novel transcriptional target of FoxO1 in pancreatic β-cells. |
| 2471 | 23705021 | FoxO1 binds to an evolutionarily conserved response element in the Ccn3 promoter to regulate its expression. |
| 2472 | 23705021 | Accordingly, CCN3 levels are elevated in pancreatic islets of mice with overexpression of a constitutively active form of FoxO1 or insulin resistance. |
| 2473 | 23705021 | Moreover, CCN3 decreases glucose oxidation, which translates into inhibition of glucose-stimulated Ca(2+) entry and insulin secretion. |
| 2474 | 23705021 | Our results identify CCN3, a novel transcriptional target of FoxO1 in pancreatic β-cells, as a potential target for therapeutic intervention in the treatment of diabetes. |
| 2475 | 23705021 | Nov/Ccn3, a novel transcriptional target of FoxO1, impairs pancreatic β-cell function. |
| 2476 | 23705021 | The forkhead transcription factor FoxO1 is a prominent mediator of insulin signaling in β-cells. |
| 2477 | 23705021 | We reasoned that identification of FoxO1 target genes in β-cells could reveal mechanisms linking β-cell dysfunction to insulin resistance. |
| 2478 | 23705021 | In this study, we report the characterization of Nov/Ccn3 as a novel transcriptional target of FoxO1 in pancreatic β-cells. |
| 2479 | 23705021 | FoxO1 binds to an evolutionarily conserved response element in the Ccn3 promoter to regulate its expression. |
| 2480 | 23705021 | Accordingly, CCN3 levels are elevated in pancreatic islets of mice with overexpression of a constitutively active form of FoxO1 or insulin resistance. |
| 2481 | 23705021 | Moreover, CCN3 decreases glucose oxidation, which translates into inhibition of glucose-stimulated Ca(2+) entry and insulin secretion. |
| 2482 | 23705021 | Our results identify CCN3, a novel transcriptional target of FoxO1 in pancreatic β-cells, as a potential target for therapeutic intervention in the treatment of diabetes. |
| 2483 | 23705021 | Nov/Ccn3, a novel transcriptional target of FoxO1, impairs pancreatic β-cell function. |
| 2484 | 23705021 | The forkhead transcription factor FoxO1 is a prominent mediator of insulin signaling in β-cells. |
| 2485 | 23705021 | We reasoned that identification of FoxO1 target genes in β-cells could reveal mechanisms linking β-cell dysfunction to insulin resistance. |
| 2486 | 23705021 | In this study, we report the characterization of Nov/Ccn3 as a novel transcriptional target of FoxO1 in pancreatic β-cells. |
| 2487 | 23705021 | FoxO1 binds to an evolutionarily conserved response element in the Ccn3 promoter to regulate its expression. |
| 2488 | 23705021 | Accordingly, CCN3 levels are elevated in pancreatic islets of mice with overexpression of a constitutively active form of FoxO1 or insulin resistance. |
| 2489 | 23705021 | Moreover, CCN3 decreases glucose oxidation, which translates into inhibition of glucose-stimulated Ca(2+) entry and insulin secretion. |
| 2490 | 23705021 | Our results identify CCN3, a novel transcriptional target of FoxO1 in pancreatic β-cells, as a potential target for therapeutic intervention in the treatment of diabetes. |
| 2491 | 23705021 | Nov/Ccn3, a novel transcriptional target of FoxO1, impairs pancreatic β-cell function. |
| 2492 | 23705021 | The forkhead transcription factor FoxO1 is a prominent mediator of insulin signaling in β-cells. |
| 2493 | 23705021 | We reasoned that identification of FoxO1 target genes in β-cells could reveal mechanisms linking β-cell dysfunction to insulin resistance. |
| 2494 | 23705021 | In this study, we report the characterization of Nov/Ccn3 as a novel transcriptional target of FoxO1 in pancreatic β-cells. |
| 2495 | 23705021 | FoxO1 binds to an evolutionarily conserved response element in the Ccn3 promoter to regulate its expression. |
| 2496 | 23705021 | Accordingly, CCN3 levels are elevated in pancreatic islets of mice with overexpression of a constitutively active form of FoxO1 or insulin resistance. |
| 2497 | 23705021 | Moreover, CCN3 decreases glucose oxidation, which translates into inhibition of glucose-stimulated Ca(2+) entry and insulin secretion. |
| 2498 | 23705021 | Our results identify CCN3, a novel transcriptional target of FoxO1 in pancreatic β-cells, as a potential target for therapeutic intervention in the treatment of diabetes. |
| 2499 | 23705021 | Nov/Ccn3, a novel transcriptional target of FoxO1, impairs pancreatic β-cell function. |
| 2500 | 23705021 | The forkhead transcription factor FoxO1 is a prominent mediator of insulin signaling in β-cells. |
| 2501 | 23705021 | We reasoned that identification of FoxO1 target genes in β-cells could reveal mechanisms linking β-cell dysfunction to insulin resistance. |
| 2502 | 23705021 | In this study, we report the characterization of Nov/Ccn3 as a novel transcriptional target of FoxO1 in pancreatic β-cells. |
| 2503 | 23705021 | FoxO1 binds to an evolutionarily conserved response element in the Ccn3 promoter to regulate its expression. |
| 2504 | 23705021 | Accordingly, CCN3 levels are elevated in pancreatic islets of mice with overexpression of a constitutively active form of FoxO1 or insulin resistance. |
| 2505 | 23705021 | Moreover, CCN3 decreases glucose oxidation, which translates into inhibition of glucose-stimulated Ca(2+) entry and insulin secretion. |
| 2506 | 23705021 | Our results identify CCN3, a novel transcriptional target of FoxO1 in pancreatic β-cells, as a potential target for therapeutic intervention in the treatment of diabetes. |
| 2507 | 23705021 | Nov/Ccn3, a novel transcriptional target of FoxO1, impairs pancreatic β-cell function. |
| 2508 | 23705021 | The forkhead transcription factor FoxO1 is a prominent mediator of insulin signaling in β-cells. |
| 2509 | 23705021 | We reasoned that identification of FoxO1 target genes in β-cells could reveal mechanisms linking β-cell dysfunction to insulin resistance. |
| 2510 | 23705021 | In this study, we report the characterization of Nov/Ccn3 as a novel transcriptional target of FoxO1 in pancreatic β-cells. |
| 2511 | 23705021 | FoxO1 binds to an evolutionarily conserved response element in the Ccn3 promoter to regulate its expression. |
| 2512 | 23705021 | Accordingly, CCN3 levels are elevated in pancreatic islets of mice with overexpression of a constitutively active form of FoxO1 or insulin resistance. |
| 2513 | 23705021 | Moreover, CCN3 decreases glucose oxidation, which translates into inhibition of glucose-stimulated Ca(2+) entry and insulin secretion. |
| 2514 | 23705021 | Our results identify CCN3, a novel transcriptional target of FoxO1 in pancreatic β-cells, as a potential target for therapeutic intervention in the treatment of diabetes. |
| 2515 | 23705021 | Nov/Ccn3, a novel transcriptional target of FoxO1, impairs pancreatic β-cell function. |
| 2516 | 23705021 | The forkhead transcription factor FoxO1 is a prominent mediator of insulin signaling in β-cells. |
| 2517 | 23705021 | We reasoned that identification of FoxO1 target genes in β-cells could reveal mechanisms linking β-cell dysfunction to insulin resistance. |
| 2518 | 23705021 | In this study, we report the characterization of Nov/Ccn3 as a novel transcriptional target of FoxO1 in pancreatic β-cells. |
| 2519 | 23705021 | FoxO1 binds to an evolutionarily conserved response element in the Ccn3 promoter to regulate its expression. |
| 2520 | 23705021 | Accordingly, CCN3 levels are elevated in pancreatic islets of mice with overexpression of a constitutively active form of FoxO1 or insulin resistance. |
| 2521 | 23705021 | Moreover, CCN3 decreases glucose oxidation, which translates into inhibition of glucose-stimulated Ca(2+) entry and insulin secretion. |
| 2522 | 23705021 | Our results identify CCN3, a novel transcriptional target of FoxO1 in pancreatic β-cells, as a potential target for therapeutic intervention in the treatment of diabetes. |
| 2523 | 23772809 | Validated targets for miR-223 that have effects on inflammation and infection include granzyme B, IKKα, Roquin and STAT3. |
| 2524 | 23772809 | With regard to cancer, validated targets include C/EBPβ, E2F1, FOXO1 and NFI-A. |
| 2525 | 23788637 | We have used in vitro and in vivo systems to show that FoxO1, an integrator of metabolic stimuli, inhibits PPARγ expression in β-cells, thus transcription of its target genes (Pdx1, glucose-dependent insulinotropic polypeptide (GIP) receptor, and pyruvate carboxylase) that are important regulators of β-cell function, survival, and compensation. |
| 2526 | 23800882 | Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes hepatic insulin clearance and endothelial survival. |
| 2527 | 23800882 | Mice lacking Ceacam1 (Cc1-/-) exhibit hyperinsulinemia, which causes insulin resistance and fatty liver. |
| 2528 | 23800882 | Basal aortic eNOS protein and NO content were reduced, in parallel with reduced Akt/eNOS and Akt/Foxo1 phosphorylation. |
| 2529 | 23800882 | Increased NADPH oxidase activity and plasma 8-isoprostane levels revealed oxidative stress and lipid peroxidation in Cc1-/- aortae. siRNA-mediated CEACAM1 knockdown in bovine aortic endothelial cells adversely affected insulin's stimulation of IRS-1/PI 3-kinase/Akt/eNOS activation by increasing IRS-1 binding to SHP2 phosphatase. |
| 2530 | 23800882 | Cc1-/- mice provide a first in vivo demonstration of distinct CEACAM1-dependent hepatic insulin clearance linking hepatic to macrovascular abnormalities. |
| 2531 | 23803610 | FOXO1 competes with carbohydrate response element-binding protein (ChREBP) and inhibits thioredoxin-interacting protein (TXNIP) transcription in pancreatic beta cells. |
| 2532 | 23803610 | The forkhead boxO1 transcription factor (FOXO1) has been reported to up-regulate TXNIP expression in neurons and endothelial cells but to down-regulate TXNIP in liver, and the effects on beta cells have remained unknown. |
| 2533 | 23803610 | We now have found that FOXO1 binds to the TXNIP promoter in vivo in human islets and INS-1 beta cells and significantly decreases TXNIP expression. |
| 2534 | 23803610 | TXNIP promoter deletion analyses revealed that an E-box motif conferring carbohydrate response element-binding protein (ChREBP)-mediated, glucose-induced TXNIP expression is necessary and sufficient for this effect, and electromobility shift assays confirmed FOXO1 binding to this site. |
| 2535 | 23803610 | Moreover, FOXO1 blocked glucose-induced TXNIP expression and reduced glucose-induced ChREBP binding at the TXNIP promoter without affecting ChREBP expression or nuclear localization, suggesting that FOXO1 may compete with ChREBP for binding to the TXNIP promoter. |
| 2536 | 23803610 | In fact, a FOXO1 DNA-binding mutant (FOXO1-H215R) failed to inhibit TXNIP transcription, and the effects were not restricted to TXNIP as FOXO1 also inhibited transcription of other ChREBP target genes such as liver pyruvate kinase. |
| 2537 | 23803610 | Together, these results demonstrate that FOXO1 inhibits beta cell TXNIP transcription and suggest that FOXO1 confers this inhibition by interfering with ChREBP DNA binding at target gene promoters. |
| 2538 | 23803610 | Our findings thereby reveal a novel gene regulatory mechanism and a previously unappreciated cross-talk between FOXO1 and ChREBP, two major metabolic signaling pathways. |
| 2539 | 23803610 | FOXO1 competes with carbohydrate response element-binding protein (ChREBP) and inhibits thioredoxin-interacting protein (TXNIP) transcription in pancreatic beta cells. |
| 2540 | 23803610 | The forkhead boxO1 transcription factor (FOXO1) has been reported to up-regulate TXNIP expression in neurons and endothelial cells but to down-regulate TXNIP in liver, and the effects on beta cells have remained unknown. |
| 2541 | 23803610 | We now have found that FOXO1 binds to the TXNIP promoter in vivo in human islets and INS-1 beta cells and significantly decreases TXNIP expression. |
| 2542 | 23803610 | TXNIP promoter deletion analyses revealed that an E-box motif conferring carbohydrate response element-binding protein (ChREBP)-mediated, glucose-induced TXNIP expression is necessary and sufficient for this effect, and electromobility shift assays confirmed FOXO1 binding to this site. |
| 2543 | 23803610 | Moreover, FOXO1 blocked glucose-induced TXNIP expression and reduced glucose-induced ChREBP binding at the TXNIP promoter without affecting ChREBP expression or nuclear localization, suggesting that FOXO1 may compete with ChREBP for binding to the TXNIP promoter. |
| 2544 | 23803610 | In fact, a FOXO1 DNA-binding mutant (FOXO1-H215R) failed to inhibit TXNIP transcription, and the effects were not restricted to TXNIP as FOXO1 also inhibited transcription of other ChREBP target genes such as liver pyruvate kinase. |
| 2545 | 23803610 | Together, these results demonstrate that FOXO1 inhibits beta cell TXNIP transcription and suggest that FOXO1 confers this inhibition by interfering with ChREBP DNA binding at target gene promoters. |
| 2546 | 23803610 | Our findings thereby reveal a novel gene regulatory mechanism and a previously unappreciated cross-talk between FOXO1 and ChREBP, two major metabolic signaling pathways. |
| 2547 | 23803610 | FOXO1 competes with carbohydrate response element-binding protein (ChREBP) and inhibits thioredoxin-interacting protein (TXNIP) transcription in pancreatic beta cells. |
| 2548 | 23803610 | The forkhead boxO1 transcription factor (FOXO1) has been reported to up-regulate TXNIP expression in neurons and endothelial cells but to down-regulate TXNIP in liver, and the effects on beta cells have remained unknown. |
| 2549 | 23803610 | We now have found that FOXO1 binds to the TXNIP promoter in vivo in human islets and INS-1 beta cells and significantly decreases TXNIP expression. |
| 2550 | 23803610 | TXNIP promoter deletion analyses revealed that an E-box motif conferring carbohydrate response element-binding protein (ChREBP)-mediated, glucose-induced TXNIP expression is necessary and sufficient for this effect, and electromobility shift assays confirmed FOXO1 binding to this site. |
| 2551 | 23803610 | Moreover, FOXO1 blocked glucose-induced TXNIP expression and reduced glucose-induced ChREBP binding at the TXNIP promoter without affecting ChREBP expression or nuclear localization, suggesting that FOXO1 may compete with ChREBP for binding to the TXNIP promoter. |
| 2552 | 23803610 | In fact, a FOXO1 DNA-binding mutant (FOXO1-H215R) failed to inhibit TXNIP transcription, and the effects were not restricted to TXNIP as FOXO1 also inhibited transcription of other ChREBP target genes such as liver pyruvate kinase. |
| 2553 | 23803610 | Together, these results demonstrate that FOXO1 inhibits beta cell TXNIP transcription and suggest that FOXO1 confers this inhibition by interfering with ChREBP DNA binding at target gene promoters. |
| 2554 | 23803610 | Our findings thereby reveal a novel gene regulatory mechanism and a previously unappreciated cross-talk between FOXO1 and ChREBP, two major metabolic signaling pathways. |
| 2555 | 23803610 | FOXO1 competes with carbohydrate response element-binding protein (ChREBP) and inhibits thioredoxin-interacting protein (TXNIP) transcription in pancreatic beta cells. |
| 2556 | 23803610 | The forkhead boxO1 transcription factor (FOXO1) has been reported to up-regulate TXNIP expression in neurons and endothelial cells but to down-regulate TXNIP in liver, and the effects on beta cells have remained unknown. |
| 2557 | 23803610 | We now have found that FOXO1 binds to the TXNIP promoter in vivo in human islets and INS-1 beta cells and significantly decreases TXNIP expression. |
| 2558 | 23803610 | TXNIP promoter deletion analyses revealed that an E-box motif conferring carbohydrate response element-binding protein (ChREBP)-mediated, glucose-induced TXNIP expression is necessary and sufficient for this effect, and electromobility shift assays confirmed FOXO1 binding to this site. |
| 2559 | 23803610 | Moreover, FOXO1 blocked glucose-induced TXNIP expression and reduced glucose-induced ChREBP binding at the TXNIP promoter without affecting ChREBP expression or nuclear localization, suggesting that FOXO1 may compete with ChREBP for binding to the TXNIP promoter. |
| 2560 | 23803610 | In fact, a FOXO1 DNA-binding mutant (FOXO1-H215R) failed to inhibit TXNIP transcription, and the effects were not restricted to TXNIP as FOXO1 also inhibited transcription of other ChREBP target genes such as liver pyruvate kinase. |
| 2561 | 23803610 | Together, these results demonstrate that FOXO1 inhibits beta cell TXNIP transcription and suggest that FOXO1 confers this inhibition by interfering with ChREBP DNA binding at target gene promoters. |
| 2562 | 23803610 | Our findings thereby reveal a novel gene regulatory mechanism and a previously unappreciated cross-talk between FOXO1 and ChREBP, two major metabolic signaling pathways. |
| 2563 | 23803610 | FOXO1 competes with carbohydrate response element-binding protein (ChREBP) and inhibits thioredoxin-interacting protein (TXNIP) transcription in pancreatic beta cells. |
| 2564 | 23803610 | The forkhead boxO1 transcription factor (FOXO1) has been reported to up-regulate TXNIP expression in neurons and endothelial cells but to down-regulate TXNIP in liver, and the effects on beta cells have remained unknown. |
| 2565 | 23803610 | We now have found that FOXO1 binds to the TXNIP promoter in vivo in human islets and INS-1 beta cells and significantly decreases TXNIP expression. |
| 2566 | 23803610 | TXNIP promoter deletion analyses revealed that an E-box motif conferring carbohydrate response element-binding protein (ChREBP)-mediated, glucose-induced TXNIP expression is necessary and sufficient for this effect, and electromobility shift assays confirmed FOXO1 binding to this site. |
| 2567 | 23803610 | Moreover, FOXO1 blocked glucose-induced TXNIP expression and reduced glucose-induced ChREBP binding at the TXNIP promoter without affecting ChREBP expression or nuclear localization, suggesting that FOXO1 may compete with ChREBP for binding to the TXNIP promoter. |
| 2568 | 23803610 | In fact, a FOXO1 DNA-binding mutant (FOXO1-H215R) failed to inhibit TXNIP transcription, and the effects were not restricted to TXNIP as FOXO1 also inhibited transcription of other ChREBP target genes such as liver pyruvate kinase. |
| 2569 | 23803610 | Together, these results demonstrate that FOXO1 inhibits beta cell TXNIP transcription and suggest that FOXO1 confers this inhibition by interfering with ChREBP DNA binding at target gene promoters. |
| 2570 | 23803610 | Our findings thereby reveal a novel gene regulatory mechanism and a previously unappreciated cross-talk between FOXO1 and ChREBP, two major metabolic signaling pathways. |
| 2571 | 23803610 | FOXO1 competes with carbohydrate response element-binding protein (ChREBP) and inhibits thioredoxin-interacting protein (TXNIP) transcription in pancreatic beta cells. |
| 2572 | 23803610 | The forkhead boxO1 transcription factor (FOXO1) has been reported to up-regulate TXNIP expression in neurons and endothelial cells but to down-regulate TXNIP in liver, and the effects on beta cells have remained unknown. |
| 2573 | 23803610 | We now have found that FOXO1 binds to the TXNIP promoter in vivo in human islets and INS-1 beta cells and significantly decreases TXNIP expression. |
| 2574 | 23803610 | TXNIP promoter deletion analyses revealed that an E-box motif conferring carbohydrate response element-binding protein (ChREBP)-mediated, glucose-induced TXNIP expression is necessary and sufficient for this effect, and electromobility shift assays confirmed FOXO1 binding to this site. |
| 2575 | 23803610 | Moreover, FOXO1 blocked glucose-induced TXNIP expression and reduced glucose-induced ChREBP binding at the TXNIP promoter without affecting ChREBP expression or nuclear localization, suggesting that FOXO1 may compete with ChREBP for binding to the TXNIP promoter. |
| 2576 | 23803610 | In fact, a FOXO1 DNA-binding mutant (FOXO1-H215R) failed to inhibit TXNIP transcription, and the effects were not restricted to TXNIP as FOXO1 also inhibited transcription of other ChREBP target genes such as liver pyruvate kinase. |
| 2577 | 23803610 | Together, these results demonstrate that FOXO1 inhibits beta cell TXNIP transcription and suggest that FOXO1 confers this inhibition by interfering with ChREBP DNA binding at target gene promoters. |
| 2578 | 23803610 | Our findings thereby reveal a novel gene regulatory mechanism and a previously unappreciated cross-talk between FOXO1 and ChREBP, two major metabolic signaling pathways. |
| 2579 | 23803610 | FOXO1 competes with carbohydrate response element-binding protein (ChREBP) and inhibits thioredoxin-interacting protein (TXNIP) transcription in pancreatic beta cells. |
| 2580 | 23803610 | The forkhead boxO1 transcription factor (FOXO1) has been reported to up-regulate TXNIP expression in neurons and endothelial cells but to down-regulate TXNIP in liver, and the effects on beta cells have remained unknown. |
| 2581 | 23803610 | We now have found that FOXO1 binds to the TXNIP promoter in vivo in human islets and INS-1 beta cells and significantly decreases TXNIP expression. |
| 2582 | 23803610 | TXNIP promoter deletion analyses revealed that an E-box motif conferring carbohydrate response element-binding protein (ChREBP)-mediated, glucose-induced TXNIP expression is necessary and sufficient for this effect, and electromobility shift assays confirmed FOXO1 binding to this site. |
| 2583 | 23803610 | Moreover, FOXO1 blocked glucose-induced TXNIP expression and reduced glucose-induced ChREBP binding at the TXNIP promoter without affecting ChREBP expression or nuclear localization, suggesting that FOXO1 may compete with ChREBP for binding to the TXNIP promoter. |
| 2584 | 23803610 | In fact, a FOXO1 DNA-binding mutant (FOXO1-H215R) failed to inhibit TXNIP transcription, and the effects were not restricted to TXNIP as FOXO1 also inhibited transcription of other ChREBP target genes such as liver pyruvate kinase. |
| 2585 | 23803610 | Together, these results demonstrate that FOXO1 inhibits beta cell TXNIP transcription and suggest that FOXO1 confers this inhibition by interfering with ChREBP DNA binding at target gene promoters. |
| 2586 | 23803610 | Our findings thereby reveal a novel gene regulatory mechanism and a previously unappreciated cross-talk between FOXO1 and ChREBP, two major metabolic signaling pathways. |
| 2587 | 23803610 | FOXO1 competes with carbohydrate response element-binding protein (ChREBP) and inhibits thioredoxin-interacting protein (TXNIP) transcription in pancreatic beta cells. |
| 2588 | 23803610 | The forkhead boxO1 transcription factor (FOXO1) has been reported to up-regulate TXNIP expression in neurons and endothelial cells but to down-regulate TXNIP in liver, and the effects on beta cells have remained unknown. |
| 2589 | 23803610 | We now have found that FOXO1 binds to the TXNIP promoter in vivo in human islets and INS-1 beta cells and significantly decreases TXNIP expression. |
| 2590 | 23803610 | TXNIP promoter deletion analyses revealed that an E-box motif conferring carbohydrate response element-binding protein (ChREBP)-mediated, glucose-induced TXNIP expression is necessary and sufficient for this effect, and electromobility shift assays confirmed FOXO1 binding to this site. |
| 2591 | 23803610 | Moreover, FOXO1 blocked glucose-induced TXNIP expression and reduced glucose-induced ChREBP binding at the TXNIP promoter without affecting ChREBP expression or nuclear localization, suggesting that FOXO1 may compete with ChREBP for binding to the TXNIP promoter. |
| 2592 | 23803610 | In fact, a FOXO1 DNA-binding mutant (FOXO1-H215R) failed to inhibit TXNIP transcription, and the effects were not restricted to TXNIP as FOXO1 also inhibited transcription of other ChREBP target genes such as liver pyruvate kinase. |
| 2593 | 23803610 | Together, these results demonstrate that FOXO1 inhibits beta cell TXNIP transcription and suggest that FOXO1 confers this inhibition by interfering with ChREBP DNA binding at target gene promoters. |
| 2594 | 23803610 | Our findings thereby reveal a novel gene regulatory mechanism and a previously unappreciated cross-talk between FOXO1 and ChREBP, two major metabolic signaling pathways. |
| 2595 | 23835335 | Genetic ablation of FoxO1 in selected hypothalamic neurons decreases food intake, increases energy expenditure, and improves glucose homeostasis, highlighting the role of this gene in insulin and leptin signaling. |
| 2596 | 23835335 | Lineage-tracing experiments showed that NPY/AgRP and POMC neurons were minimally affected by the knockout. |
| 2597 | 23884882 | HFS diets also resulted in decreased expression of essential β-cell transcription factors forkhead box O1 (FOXO1), NKX6-1, NKX2-2, and PDX1, which did not occur with resveratrol supplementation. |
| 2598 | 20736318 | The forkhead transcription factor forkhead box O1 (Foxo1) plays a crucial role in mediating the effect of insulin on hepatic gluconeogenesis. |
| 2599 | 20736318 | Using mass spectrometric affinity screening, we discovered a series of compounds that bind to Foxo1, identifying among them the compound, 5-amino-7-(cyclohexylamino)-1-ethyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (AS1842856), which potently inhibits human Foxo1 transactivation and reduces glucose production through the inhibition of glucose-6 phosphatase and phosphoenolpyruvate carboxykinase mRNA levels in a rat hepatic cell line. |
| 2600 | 20736318 | The forkhead transcription factor forkhead box O1 (Foxo1) plays a crucial role in mediating the effect of insulin on hepatic gluconeogenesis. |
| 2601 | 20736318 | Using mass spectrometric affinity screening, we discovered a series of compounds that bind to Foxo1, identifying among them the compound, 5-amino-7-(cyclohexylamino)-1-ethyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (AS1842856), which potently inhibits human Foxo1 transactivation and reduces glucose production through the inhibition of glucose-6 phosphatase and phosphoenolpyruvate carboxykinase mRNA levels in a rat hepatic cell line. |