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Gene Information
Gene symbol: STAT3
Gene name: signal transducer and activator of transcription 3 (acute-phase response factor)
HGNC ID: 11364
Synonyms: APRF
Related Genes
Related Sentences
| # | PMID | Sentence |
| 1 | 8692797 | Defective STAT signaling by the leptin receptor in diabetic mice. |
| 2 | 8692797 | Leptin and its receptor, obese receptor (OB-R), comprise an important signaling system for the regulation of body weight. |
| 3 | 8692797 | We cloned a long isoform of the wild-type leptin receptor that is preferentially expressed in the hypothalamus and show that it can activate signal transducers and activators of transcription (STAT)-3, STAT-5, and STAT-6. |
| 4 | 8692797 | These data provide further evidence that the mutation in OB-R causes the db/db phenotype and identify three STAT proteins as potential mediators of the anti-obesity effects of leptin. |
| 5 | 9218758 | Molecular role of TGF-beta, secreted from a new type of CD4+ suppressor T cell, NY4.2, in the prevention of autoimmune IDDM in NOD mice. |
| 6 | 9218758 | A new type of CD4+ T cell clone (NY4.2) isolated from pancreatic islet-infiltrated lymphocytes of acutely diabetic non-obese diabetic (NOD) mice prevents the development of insulin-dependent diabetes mellitus (IDDM) in NOD mice, as well as the recurrence of autoimmune diabetes in syngeneic islet-transplanted NOD mice. |
| 7 | 9218758 | This investigation was initiated to determine the molecular role TGF-beta plays in the prevention of autoimmune IDDM by determining its effect on IL-2-induced signal transduction in Con A-activated NOD mouse splenocytes and HT-2 cells. |
| 8 | 9218758 | Second, we determined whether TGF-beta inhibits the activation of Janus kinases (JAKs), as well as signal transducers and activators of transcription (STAT) proteins, involved in an IL-2-induced signalling pathway that normally leads to the proliferation of T cells. |
| 9 | 9218758 | We found that TGF-beta inhibited tyrosine phosphorylation of JAK1, JAK3, STAT3 and STAT5 in Con A blasts from NOD splenocytes and HT-2 cells. |
| 10 | 9218758 | Third, we examined whether TGF-beta inhibits the cooperation between STAT proteins and mitogen-activated protein kinase (MAPK), especially extracellular signal-regulated kinase 2 (ERK2). |
| 11 | 9218758 | We found that TGF-beta inhibited the association of STAT3 and STAT5 with ERK2 in Con A blasts from NOD splenocytes and HT-2 cells. |
| 12 | 9218758 | On the basis of these observations, we conclude that TGF-beta may interfere with signal transduction via inhibition of the IL-2-induced JAK/STAT pathway and inhibition of the association of STAT proteins with ERK2 in T cells from NOD splenocytes, resulting in the inhibition of IL-2-dependent T cell proliferation. |
| 13 | 9218758 | TGF-beta-mediated suppression of T cell activation may be responsible for the prevention of effector T cell-mediated autoimmune IDDM in NOD mice by TGF-beta-producing CD4+ suppressor T cells. |
| 14 | 9218758 | Molecular role of TGF-beta, secreted from a new type of CD4+ suppressor T cell, NY4.2, in the prevention of autoimmune IDDM in NOD mice. |
| 15 | 9218758 | A new type of CD4+ T cell clone (NY4.2) isolated from pancreatic islet-infiltrated lymphocytes of acutely diabetic non-obese diabetic (NOD) mice prevents the development of insulin-dependent diabetes mellitus (IDDM) in NOD mice, as well as the recurrence of autoimmune diabetes in syngeneic islet-transplanted NOD mice. |
| 16 | 9218758 | This investigation was initiated to determine the molecular role TGF-beta plays in the prevention of autoimmune IDDM by determining its effect on IL-2-induced signal transduction in Con A-activated NOD mouse splenocytes and HT-2 cells. |
| 17 | 9218758 | Second, we determined whether TGF-beta inhibits the activation of Janus kinases (JAKs), as well as signal transducers and activators of transcription (STAT) proteins, involved in an IL-2-induced signalling pathway that normally leads to the proliferation of T cells. |
| 18 | 9218758 | We found that TGF-beta inhibited tyrosine phosphorylation of JAK1, JAK3, STAT3 and STAT5 in Con A blasts from NOD splenocytes and HT-2 cells. |
| 19 | 9218758 | Third, we examined whether TGF-beta inhibits the cooperation between STAT proteins and mitogen-activated protein kinase (MAPK), especially extracellular signal-regulated kinase 2 (ERK2). |
| 20 | 9218758 | We found that TGF-beta inhibited the association of STAT3 and STAT5 with ERK2 in Con A blasts from NOD splenocytes and HT-2 cells. |
| 21 | 9218758 | On the basis of these observations, we conclude that TGF-beta may interfere with signal transduction via inhibition of the IL-2-induced JAK/STAT pathway and inhibition of the association of STAT proteins with ERK2 in T cells from NOD splenocytes, resulting in the inhibition of IL-2-dependent T cell proliferation. |
| 22 | 9218758 | TGF-beta-mediated suppression of T cell activation may be responsible for the prevention of effector T cell-mediated autoimmune IDDM in NOD mice by TGF-beta-producing CD4+ suppressor T cells. |
| 23 | 9751766 | Overexpression of leptin receptors in pancreatic islets of Zucker diabetic fatty rats restores GLUT-2, glucokinase, and glucose-stimulated insulin secretion. |
| 24 | 9751766 | The high-Km glucose transporter, GLUT-2, and the high-Km hexokinase of beta cells, glucokinase (GK), are required for glucose-stimulated insulin secretion (GSIS). |
| 25 | 9751766 | Leptin induced a rise in phosphorylated STAT3, indicating that the transferred wild-type OB-R was functional. |
| 26 | 9751766 | GLUT-2 protein rose 17-fold in AdCMV-OB-Rb-treated ZDF islets without leptin, and leptin caused no further rise. |
| 27 | 9751766 | Clofibrate and 9-cis-retinoic acid, the partner ligands for binding to peroxisome proliferator-activator receptor alpha (PPARalpha) and retinoid X receptor, up-regulated GLUT-2 expression in islets of normal rats, but not in ZDF rats, in which PPARalpha is very low. |
| 28 | 9751766 | Because the fat content of islets of diabetic ZDF rats remains high unless they are treated with leptin, it appears that restoration of GSIS requires normalization of intracellular nutrient homeostasis, whereas up-regulation of GLUT-2 and GK is leptin-independent, requiring only high expression of OB-Rb. |
| 29 | 9794450 | Leptin has been shown to activate multiple signaling molecules in cultured cells, including Janus kinase-2, STAT (signal transducer and activator of transcription) proteins, and mitogen-activated protein kinase, and to stimulate the DNA-binding activity of STAT3 in mouse hypothalamus. |
| 30 | 9794450 | STAT3 phosphorylation was first evident at 5 min and was maximal at 30 min after leptin injection. |
| 31 | 9794450 | By contrast, leptin did not increase the phosphorylation of Janus kinase proteins, mitogen-activated protein kinase, or STAT1 and -5 despite abundant expression of these signaling molecules in the hypothalamus. |
| 32 | 9794450 | It remains unclear how signaling is propagated downstream from the leptin receptor to STAT3, but this may involve novel signaling intermediates. |
| 33 | 9794450 | Leptin has been shown to activate multiple signaling molecules in cultured cells, including Janus kinase-2, STAT (signal transducer and activator of transcription) proteins, and mitogen-activated protein kinase, and to stimulate the DNA-binding activity of STAT3 in mouse hypothalamus. |
| 34 | 9794450 | STAT3 phosphorylation was first evident at 5 min and was maximal at 30 min after leptin injection. |
| 35 | 9794450 | By contrast, leptin did not increase the phosphorylation of Janus kinase proteins, mitogen-activated protein kinase, or STAT1 and -5 despite abundant expression of these signaling molecules in the hypothalamus. |
| 36 | 9794450 | It remains unclear how signaling is propagated downstream from the leptin receptor to STAT3, but this may involve novel signaling intermediates. |
| 37 | 9794450 | Leptin has been shown to activate multiple signaling molecules in cultured cells, including Janus kinase-2, STAT (signal transducer and activator of transcription) proteins, and mitogen-activated protein kinase, and to stimulate the DNA-binding activity of STAT3 in mouse hypothalamus. |
| 38 | 9794450 | STAT3 phosphorylation was first evident at 5 min and was maximal at 30 min after leptin injection. |
| 39 | 9794450 | By contrast, leptin did not increase the phosphorylation of Janus kinase proteins, mitogen-activated protein kinase, or STAT1 and -5 despite abundant expression of these signaling molecules in the hypothalamus. |
| 40 | 9794450 | It remains unclear how signaling is propagated downstream from the leptin receptor to STAT3, but this may involve novel signaling intermediates. |
| 41 | 9923604 | Interleukin-1beta activates a short STAT-3 isoform in clonal insulin-secreting cells. |
| 42 | 9923604 | In the present work we describe induction of DNA binding activity to signal transducer and activator of transcription (STAT) in response to IL-1beta in clonal insulin-secreting cells. |
| 43 | 9923604 | Moreover, IL-1beta activates a short isoform of STAT-3 that potently stimulates transcription. |
| 44 | 9923604 | Immunoprecipitation studies reveal an interaction between the activated STAT-3 and the IL-1 receptor accessory protein indicating an association between the two signaling pathways. |
| 45 | 9923604 | Interleukin-1beta activates a short STAT-3 isoform in clonal insulin-secreting cells. |
| 46 | 9923604 | In the present work we describe induction of DNA binding activity to signal transducer and activator of transcription (STAT) in response to IL-1beta in clonal insulin-secreting cells. |
| 47 | 9923604 | Moreover, IL-1beta activates a short isoform of STAT-3 that potently stimulates transcription. |
| 48 | 9923604 | Immunoprecipitation studies reveal an interaction between the activated STAT-3 and the IL-1 receptor accessory protein indicating an association between the two signaling pathways. |
| 49 | 9923604 | Interleukin-1beta activates a short STAT-3 isoform in clonal insulin-secreting cells. |
| 50 | 9923604 | In the present work we describe induction of DNA binding activity to signal transducer and activator of transcription (STAT) in response to IL-1beta in clonal insulin-secreting cells. |
| 51 | 9923604 | Moreover, IL-1beta activates a short isoform of STAT-3 that potently stimulates transcription. |
| 52 | 9923604 | Immunoprecipitation studies reveal an interaction between the activated STAT-3 and the IL-1 receptor accessory protein indicating an association between the two signaling pathways. |
| 53 | 9930929 | Increased mitotic activity has been seen both in vivo and in vitro in islets exposed to placental lactogen (PL), prolactin (PRL) and growth hormone (GH). |
| 54 | 9930929 | Thus the mitotic signaling only requires the membrane proximal part of the receptor and activation of the tyrosine kinase JAK2 and the transcription factors STAT1 and 3. |
| 55 | 9930929 | In order to identify putative autocrine growth factors or targets for growth factors we have cloned a novel GH/PRL stimulated rat islet gene product, Pref-1 (preadipocyte factor-1). |
| 56 | 10051633 | In addition to causing abnormal MHC expression, the ds nucleic acids increase the expression of genes necessary for antigen processing and presentation: proteasome proteins (e.g., LMP2), transporters of antigen peptides; invariant chain, HLA-DM, and the costimulatory molecule B7.1. |
| 57 | 10051633 | The ds nucleic acids also induce or activate Stat1, Stat3, mitogen-activated protein kinase, NF-kappaB, the class II transactivator, RFX5, and the IFN regulatory factor 1 differently from gammaIFN. |
| 58 | 10194520 | Leptin signalling in pancreatic islets and clonal insulin-secreting cells. |
| 59 | 10194520 | In addition to its anorectic and thermogenic central actions, leptin is known to act on peripheral tissues, including the pancreatic beta-cell where it inhibits insulin secretion and reduces insulin transcript levels. |
| 60 | 10194520 | In the present study, we show that leptin activates a signal transducer and activator of transcription (STAT)3 signalling mechanism in pancreatic islets and in a rat model of the pancreatic beta-cell, RINm5F. |
| 61 | 10194520 | Leptin induced DNA binding to a STAT consensus oligonucleotide and resulted in transcriptional activation from STAT reporter constructs in a manner consistent with STAT3 activation. |
| 62 | 10194520 | Conditions that mimic increased metabolic activity resulted in attenuation of leptin-mediated STAT DNA binding but had no significant effect on STAT3 tyrosine phosphorylation in RINm5F cells. |
| 63 | 10194520 | In addition, leptin activated the mitogen activated protein (MAP) kinase pathway in RINm5F cells. |
| 64 | 10194520 | Leptin signalling in pancreatic islets and clonal insulin-secreting cells. |
| 65 | 10194520 | In addition to its anorectic and thermogenic central actions, leptin is known to act on peripheral tissues, including the pancreatic beta-cell where it inhibits insulin secretion and reduces insulin transcript levels. |
| 66 | 10194520 | In the present study, we show that leptin activates a signal transducer and activator of transcription (STAT)3 signalling mechanism in pancreatic islets and in a rat model of the pancreatic beta-cell, RINm5F. |
| 67 | 10194520 | Leptin induced DNA binding to a STAT consensus oligonucleotide and resulted in transcriptional activation from STAT reporter constructs in a manner consistent with STAT3 activation. |
| 68 | 10194520 | Conditions that mimic increased metabolic activity resulted in attenuation of leptin-mediated STAT DNA binding but had no significant effect on STAT3 tyrosine phosphorylation in RINm5F cells. |
| 69 | 10194520 | In addition, leptin activated the mitogen activated protein (MAP) kinase pathway in RINm5F cells. |
| 70 | 10194520 | Leptin signalling in pancreatic islets and clonal insulin-secreting cells. |
| 71 | 10194520 | In addition to its anorectic and thermogenic central actions, leptin is known to act on peripheral tissues, including the pancreatic beta-cell where it inhibits insulin secretion and reduces insulin transcript levels. |
| 72 | 10194520 | In the present study, we show that leptin activates a signal transducer and activator of transcription (STAT)3 signalling mechanism in pancreatic islets and in a rat model of the pancreatic beta-cell, RINm5F. |
| 73 | 10194520 | Leptin induced DNA binding to a STAT consensus oligonucleotide and resulted in transcriptional activation from STAT reporter constructs in a manner consistent with STAT3 activation. |
| 74 | 10194520 | Conditions that mimic increased metabolic activity resulted in attenuation of leptin-mediated STAT DNA binding but had no significant effect on STAT3 tyrosine phosphorylation in RINm5F cells. |
| 75 | 10194520 | In addition, leptin activated the mitogen activated protein (MAP) kinase pathway in RINm5F cells. |
| 76 | 10799542 | We have investigated the signaling function of mutant LRb intracellular domains under the control of the extracellular erythropoietin (Epo) receptor. |
| 77 | 10799542 | By using this system, we confirm that two tyrosine residues in the intracellular domain of murine LRb become phosphorylated to mediate LRb signaling; Tyr(985) controls the tyrosine phosphorylation of SHP-2, and Tyr(1138) controls STAT3 activation. |
| 78 | 10799542 | We furthermore investigated the mechanisms by which LRb controls downstream ERK activation and c-fos and SOCS3 message accumulation. |
| 79 | 10799542 | Tyr(985)-mediated recruitment of SHP-2 does not alter tyrosine phosphorylation of Jak2 or STAT3 but results in GRB-2 binding to tyrosine-phosphorylated SHP-2 and is required for the majority of ERK activation during LRb signaling. |
| 80 | 10799542 | Tyr(985) and ERK activation similarly mediate c-fos mRNA accumulation. |
| 81 | 10799542 | In contrast, SOCS3 mRNA accumulation requires Tyr(1138)-mediated STAT3 activation. |
| 82 | 10799542 | Thus, the two LRb tyrosine residues that are phosphorylated during receptor activation mediate distinct signaling pathways as follows: SHP-2 binding to Tyr(985) positively regulates the ERK --> c-fos pathway, and STAT3 binding to Tyr(1138) mediates the inhibitory SOCS3 pathway. |
| 83 | 10799542 | We have investigated the signaling function of mutant LRb intracellular domains under the control of the extracellular erythropoietin (Epo) receptor. |
| 84 | 10799542 | By using this system, we confirm that two tyrosine residues in the intracellular domain of murine LRb become phosphorylated to mediate LRb signaling; Tyr(985) controls the tyrosine phosphorylation of SHP-2, and Tyr(1138) controls STAT3 activation. |
| 85 | 10799542 | We furthermore investigated the mechanisms by which LRb controls downstream ERK activation and c-fos and SOCS3 message accumulation. |
| 86 | 10799542 | Tyr(985)-mediated recruitment of SHP-2 does not alter tyrosine phosphorylation of Jak2 or STAT3 but results in GRB-2 binding to tyrosine-phosphorylated SHP-2 and is required for the majority of ERK activation during LRb signaling. |
| 87 | 10799542 | Tyr(985) and ERK activation similarly mediate c-fos mRNA accumulation. |
| 88 | 10799542 | In contrast, SOCS3 mRNA accumulation requires Tyr(1138)-mediated STAT3 activation. |
| 89 | 10799542 | Thus, the two LRb tyrosine residues that are phosphorylated during receptor activation mediate distinct signaling pathways as follows: SHP-2 binding to Tyr(985) positively regulates the ERK --> c-fos pathway, and STAT3 binding to Tyr(1138) mediates the inhibitory SOCS3 pathway. |
| 90 | 10799542 | We have investigated the signaling function of mutant LRb intracellular domains under the control of the extracellular erythropoietin (Epo) receptor. |
| 91 | 10799542 | By using this system, we confirm that two tyrosine residues in the intracellular domain of murine LRb become phosphorylated to mediate LRb signaling; Tyr(985) controls the tyrosine phosphorylation of SHP-2, and Tyr(1138) controls STAT3 activation. |
| 92 | 10799542 | We furthermore investigated the mechanisms by which LRb controls downstream ERK activation and c-fos and SOCS3 message accumulation. |
| 93 | 10799542 | Tyr(985)-mediated recruitment of SHP-2 does not alter tyrosine phosphorylation of Jak2 or STAT3 but results in GRB-2 binding to tyrosine-phosphorylated SHP-2 and is required for the majority of ERK activation during LRb signaling. |
| 94 | 10799542 | Tyr(985) and ERK activation similarly mediate c-fos mRNA accumulation. |
| 95 | 10799542 | In contrast, SOCS3 mRNA accumulation requires Tyr(1138)-mediated STAT3 activation. |
| 96 | 10799542 | Thus, the two LRb tyrosine residues that are phosphorylated during receptor activation mediate distinct signaling pathways as follows: SHP-2 binding to Tyr(985) positively regulates the ERK --> c-fos pathway, and STAT3 binding to Tyr(1138) mediates the inhibitory SOCS3 pathway. |
| 97 | 10799542 | We have investigated the signaling function of mutant LRb intracellular domains under the control of the extracellular erythropoietin (Epo) receptor. |
| 98 | 10799542 | By using this system, we confirm that two tyrosine residues in the intracellular domain of murine LRb become phosphorylated to mediate LRb signaling; Tyr(985) controls the tyrosine phosphorylation of SHP-2, and Tyr(1138) controls STAT3 activation. |
| 99 | 10799542 | We furthermore investigated the mechanisms by which LRb controls downstream ERK activation and c-fos and SOCS3 message accumulation. |
| 100 | 10799542 | Tyr(985)-mediated recruitment of SHP-2 does not alter tyrosine phosphorylation of Jak2 or STAT3 but results in GRB-2 binding to tyrosine-phosphorylated SHP-2 and is required for the majority of ERK activation during LRb signaling. |
| 101 | 10799542 | Tyr(985) and ERK activation similarly mediate c-fos mRNA accumulation. |
| 102 | 10799542 | In contrast, SOCS3 mRNA accumulation requires Tyr(1138)-mediated STAT3 activation. |
| 103 | 10799542 | Thus, the two LRb tyrosine residues that are phosphorylated during receptor activation mediate distinct signaling pathways as follows: SHP-2 binding to Tyr(985) positively regulates the ERK --> c-fos pathway, and STAT3 binding to Tyr(1138) mediates the inhibitory SOCS3 pathway. |
| 104 | 10908145 | The transcription factor Stat5a critically mediates prolactin (PRL)-induced mammary gland development and lactogenesis. |
| 105 | 10908145 | Serum testosterone and PRL levels were normal in Stat5a knockout mice, but prostate PRL receptor expression was reduced as determined by immunohistochemistry. |
| 106 | 10908145 | Expression levels or activation states of other PRL signal transduction proteins, including Stat5b, Stat3, Stat1, ERK1, and ERK2 were not altered. |
| 107 | 11018044 | SOCS3 mediates feedback inhibition of the leptin receptor via Tyr985. |
| 108 | 11018044 | Phosphorylated Tyr(1138) binds STAT3 to mediate its tyrosine phosphorylation and transcriptional activation, while phosphorylated Tyr(985) binds the tyrosine phosphatase SHP-2 and reportedly mediates both activation of ERK kinases and inhibition of LRb-mediated STAT3 activation. |
| 109 | 11018044 | We show here that although mutation of Tyr(985) does not alter STAT3 signaling by erythropoietin receptor-LRb (ELR) chimeras in transfected 293 cells at short times of stimulation, this mutation enhances STAT3 signaling at longer times of stimulation (>6 h). |
| 110 | 11018044 | Additionally, overexpression of SOCS3, but not SHP-2, impairs ELR signaling, and the overexpression of SHP-2 blunts SOCS3-mediated inhibition of ELR signaling. |
| 111 | 11018044 | Thus, our data suggest that in addition to mediating SHP-2 binding and ERK activation during acute stimulation, Tyr(985) of LRb mediates feedback inhibition of LRb signaling by binding to LRb-induced SOCS3. |
| 112 | 11018044 | SOCS3 mediates feedback inhibition of the leptin receptor via Tyr985. |
| 113 | 11018044 | Phosphorylated Tyr(1138) binds STAT3 to mediate its tyrosine phosphorylation and transcriptional activation, while phosphorylated Tyr(985) binds the tyrosine phosphatase SHP-2 and reportedly mediates both activation of ERK kinases and inhibition of LRb-mediated STAT3 activation. |
| 114 | 11018044 | We show here that although mutation of Tyr(985) does not alter STAT3 signaling by erythropoietin receptor-LRb (ELR) chimeras in transfected 293 cells at short times of stimulation, this mutation enhances STAT3 signaling at longer times of stimulation (>6 h). |
| 115 | 11018044 | Additionally, overexpression of SOCS3, but not SHP-2, impairs ELR signaling, and the overexpression of SHP-2 blunts SOCS3-mediated inhibition of ELR signaling. |
| 116 | 11018044 | Thus, our data suggest that in addition to mediating SHP-2 binding and ERK activation during acute stimulation, Tyr(985) of LRb mediates feedback inhibition of LRb signaling by binding to LRb-induced SOCS3. |
| 117 | 11161808 | Structure of the mouse Stat 3/5 locus: evolution from Drosophila to zebrafish to mouse. |
| 118 | 11161808 | While Drosophila contains only one Stat (d-Stat), mammals contain seven, with STATs 3, 5a, and 5b being the closest functional relatives. |
| 119 | 11161808 | To understand the evolutionary relationship between d-Stat and vertebrate STATs 3 and 5, we isolated, sequenced, and analyzed the zebrafish Stat3 (z-Stat3) gene and a 500-kb region spanning mouse chromosome 11, 60.5 cM containing three Stat genes (m-Stats). |
| 120 | 11161808 | Within this region we identified the genes encoding m-Stats 3, 5a, and 5b, Cnp1, Hcrt/Orexin, Ptrf, GCN5, mDj11, and four new genes. |
| 121 | 11161808 | The 5' ends of the m-Stat5a and m-Stat5b genes are juxtaposed to each other, and the 3' ends of the m-Stat3 and Stat5a genes face each other. |
| 122 | 11161808 | We propose that the Stat3 and Stat5 lineages are derived from the duplication of a common primordial gene and that d-Stat is a part of the Stat5 lineage. |
| 123 | 11161808 | Structure of the mouse Stat 3/5 locus: evolution from Drosophila to zebrafish to mouse. |
| 124 | 11161808 | While Drosophila contains only one Stat (d-Stat), mammals contain seven, with STATs 3, 5a, and 5b being the closest functional relatives. |
| 125 | 11161808 | To understand the evolutionary relationship between d-Stat and vertebrate STATs 3 and 5, we isolated, sequenced, and analyzed the zebrafish Stat3 (z-Stat3) gene and a 500-kb region spanning mouse chromosome 11, 60.5 cM containing three Stat genes (m-Stats). |
| 126 | 11161808 | Within this region we identified the genes encoding m-Stats 3, 5a, and 5b, Cnp1, Hcrt/Orexin, Ptrf, GCN5, mDj11, and four new genes. |
| 127 | 11161808 | The 5' ends of the m-Stat5a and m-Stat5b genes are juxtaposed to each other, and the 3' ends of the m-Stat3 and Stat5a genes face each other. |
| 128 | 11161808 | We propose that the Stat3 and Stat5 lineages are derived from the duplication of a common primordial gene and that d-Stat is a part of the Stat5 lineage. |
| 129 | 11161808 | Structure of the mouse Stat 3/5 locus: evolution from Drosophila to zebrafish to mouse. |
| 130 | 11161808 | While Drosophila contains only one Stat (d-Stat), mammals contain seven, with STATs 3, 5a, and 5b being the closest functional relatives. |
| 131 | 11161808 | To understand the evolutionary relationship between d-Stat and vertebrate STATs 3 and 5, we isolated, sequenced, and analyzed the zebrafish Stat3 (z-Stat3) gene and a 500-kb region spanning mouse chromosome 11, 60.5 cM containing three Stat genes (m-Stats). |
| 132 | 11161808 | Within this region we identified the genes encoding m-Stats 3, 5a, and 5b, Cnp1, Hcrt/Orexin, Ptrf, GCN5, mDj11, and four new genes. |
| 133 | 11161808 | The 5' ends of the m-Stat5a and m-Stat5b genes are juxtaposed to each other, and the 3' ends of the m-Stat3 and Stat5a genes face each other. |
| 134 | 11161808 | We propose that the Stat3 and Stat5 lineages are derived from the duplication of a common primordial gene and that d-Stat is a part of the Stat5 lineage. |
| 135 | 11161808 | Structure of the mouse Stat 3/5 locus: evolution from Drosophila to zebrafish to mouse. |
| 136 | 11161808 | While Drosophila contains only one Stat (d-Stat), mammals contain seven, with STATs 3, 5a, and 5b being the closest functional relatives. |
| 137 | 11161808 | To understand the evolutionary relationship between d-Stat and vertebrate STATs 3 and 5, we isolated, sequenced, and analyzed the zebrafish Stat3 (z-Stat3) gene and a 500-kb region spanning mouse chromosome 11, 60.5 cM containing three Stat genes (m-Stats). |
| 138 | 11161808 | Within this region we identified the genes encoding m-Stats 3, 5a, and 5b, Cnp1, Hcrt/Orexin, Ptrf, GCN5, mDj11, and four new genes. |
| 139 | 11161808 | The 5' ends of the m-Stat5a and m-Stat5b genes are juxtaposed to each other, and the 3' ends of the m-Stat3 and Stat5a genes face each other. |
| 140 | 11161808 | We propose that the Stat3 and Stat5 lineages are derived from the duplication of a common primordial gene and that d-Stat is a part of the Stat5 lineage. |
| 141 | 11161808 | Structure of the mouse Stat 3/5 locus: evolution from Drosophila to zebrafish to mouse. |
| 142 | 11161808 | While Drosophila contains only one Stat (d-Stat), mammals contain seven, with STATs 3, 5a, and 5b being the closest functional relatives. |
| 143 | 11161808 | To understand the evolutionary relationship between d-Stat and vertebrate STATs 3 and 5, we isolated, sequenced, and analyzed the zebrafish Stat3 (z-Stat3) gene and a 500-kb region spanning mouse chromosome 11, 60.5 cM containing three Stat genes (m-Stats). |
| 144 | 11161808 | Within this region we identified the genes encoding m-Stats 3, 5a, and 5b, Cnp1, Hcrt/Orexin, Ptrf, GCN5, mDj11, and four new genes. |
| 145 | 11161808 | The 5' ends of the m-Stat5a and m-Stat5b genes are juxtaposed to each other, and the 3' ends of the m-Stat3 and Stat5a genes face each other. |
| 146 | 11161808 | We propose that the Stat3 and Stat5 lineages are derived from the duplication of a common primordial gene and that d-Stat is a part of the Stat5 lineage. |
| 147 | 11245612 | We correlated the levels of specific regulators of insulin signaling and adipocyte differentiation with these phenotypic changes in adipose tissue. |
| 148 | 11245612 | Signal transducers and activators of transcription (STAT)1, STAT3, and peroxisome proliferator-activated receptor (PPAR)-gamma protein levels were elevated in the transgenic mice. |
| 149 | 11245612 | We hypothesize that agouti increases adiposity and promotes insulin sensitivity by acting directly on adipocytes via PPAR-gamma. |
| 150 | 11334438 | Insulin and leptin acutely regulate cholesterol ester metabolism in macrophages by novel signaling pathways. |
| 151 | 11334438 | Leptin also stimulates both phosphoinositide 3-kinase (PI 3-kinase) activity and tyrosine phosphorylation of JAK2 and STAT3 in these cells. |
| 152 | 11334438 | We investigated the effects of leptin on hormone-sensitive lipase (HSL), which acts as a neutral cholesterol esterase in macrophages and is a rate-limiting step in cholesterol ester breakdown. |
| 153 | 11334438 | Leptin significantly increased HSL activity in J774.2 macrophages, and these effects were additive with the effects of cAMP and were blocked by PI 3-kinase inhibitors. |
| 154 | 11334438 | Conversely, insulin inhibited HSL in macrophages, but unlike adipocytes, this effect did not require PI 3-kinase. |
| 155 | 11334438 | These results indicate that leptin and insulin regulate cholesterol-ester homeostasis in macrophages and, therefore, defects in this process caused by leptin and/or insulin resistance could contribute to the increased incidence of atherosclerosis found associated with obesity and type 2 diabetes. |
| 156 | 11416024 | Leptin and tumor necrosis factor-alpha induce the tyrosine phosphorylation of signal transducer and activator of transcription proteins in the hypothalamus of normal rats in vivo. |
| 157 | 11416024 | However, TNFalpha signaling in the brain and the potential interaction with leptin have not been investigated to date. |
| 158 | 11416024 | Here we studied the tyrosine phosphorylation of STAT (signal transducer and activator of transcription) proteins in the hypothalamus of normal rats after iv injection of recombinant murine leptin or TNFalpha or coinjection of both cytokines. |
| 159 | 11416024 | Immunoblot analysis of hypothalamic lysates with a phospho-specific STAT3 antibody showed a 6- to 7-fold stimulation of STAT3 tyrosine phosphorylation in response to both leptin and TNFalpha. |
| 160 | 11416024 | No other STAT proteins (STAT1, STAT5) were activated by leptin, whereas TNFalpha injection resulted in a dose-dependent phosphorylation of hypothalamic STAT5. |
| 161 | 11416024 | In contrast to its action in the brain, leptin was unable to produce STAT3 phosphorylation in the liver, either alone or in combination with TNFalpha. |
| 162 | 11416024 | These data show that TNFalpha, independently of leptin, activates hypothalamic STAT signaling pathways and enhances leptin action at the level of STAT3. |
| 163 | 11416024 | We therefore suggest that TNFalpha may represent a modulator of leptin action in the hypothalamus. |
| 164 | 11416024 | Leptin and tumor necrosis factor-alpha induce the tyrosine phosphorylation of signal transducer and activator of transcription proteins in the hypothalamus of normal rats in vivo. |
| 165 | 11416024 | However, TNFalpha signaling in the brain and the potential interaction with leptin have not been investigated to date. |
| 166 | 11416024 | Here we studied the tyrosine phosphorylation of STAT (signal transducer and activator of transcription) proteins in the hypothalamus of normal rats after iv injection of recombinant murine leptin or TNFalpha or coinjection of both cytokines. |
| 167 | 11416024 | Immunoblot analysis of hypothalamic lysates with a phospho-specific STAT3 antibody showed a 6- to 7-fold stimulation of STAT3 tyrosine phosphorylation in response to both leptin and TNFalpha. |
| 168 | 11416024 | No other STAT proteins (STAT1, STAT5) were activated by leptin, whereas TNFalpha injection resulted in a dose-dependent phosphorylation of hypothalamic STAT5. |
| 169 | 11416024 | In contrast to its action in the brain, leptin was unable to produce STAT3 phosphorylation in the liver, either alone or in combination with TNFalpha. |
| 170 | 11416024 | These data show that TNFalpha, independently of leptin, activates hypothalamic STAT signaling pathways and enhances leptin action at the level of STAT3. |
| 171 | 11416024 | We therefore suggest that TNFalpha may represent a modulator of leptin action in the hypothalamus. |
| 172 | 11416024 | Leptin and tumor necrosis factor-alpha induce the tyrosine phosphorylation of signal transducer and activator of transcription proteins in the hypothalamus of normal rats in vivo. |
| 173 | 11416024 | However, TNFalpha signaling in the brain and the potential interaction with leptin have not been investigated to date. |
| 174 | 11416024 | Here we studied the tyrosine phosphorylation of STAT (signal transducer and activator of transcription) proteins in the hypothalamus of normal rats after iv injection of recombinant murine leptin or TNFalpha or coinjection of both cytokines. |
| 175 | 11416024 | Immunoblot analysis of hypothalamic lysates with a phospho-specific STAT3 antibody showed a 6- to 7-fold stimulation of STAT3 tyrosine phosphorylation in response to both leptin and TNFalpha. |
| 176 | 11416024 | No other STAT proteins (STAT1, STAT5) were activated by leptin, whereas TNFalpha injection resulted in a dose-dependent phosphorylation of hypothalamic STAT5. |
| 177 | 11416024 | In contrast to its action in the brain, leptin was unable to produce STAT3 phosphorylation in the liver, either alone or in combination with TNFalpha. |
| 178 | 11416024 | These data show that TNFalpha, independently of leptin, activates hypothalamic STAT signaling pathways and enhances leptin action at the level of STAT3. |
| 179 | 11416024 | We therefore suggest that TNFalpha may represent a modulator of leptin action in the hypothalamus. |
| 180 | 11701441 | Evidence against high glucose as a mediator of ERK1/2 or p38 MAPK phosphorylation in rat skeletal muscle. |
| 181 | 11701441 | Exposure of muscle to either hyperosmosis (600 mM mannitol) or insulin (6 nM) led to a marked increase in extracellular signal-regulated protein kinase (ERK)1/2 phosphorylation. |
| 182 | 11701441 | Hyperosmosis elicited a 5.2-fold increase in p38 phosphorylation (P < 0.05), whereas insulin was without effect. |
| 183 | 11701441 | No effect of high glucose was noted on signal transduction to signal transducer and activator of transcription 3 and Akt. |
| 184 | 11701441 | In conclusion, short-term exposure of skeletal muscle to high levels of glucose does not appear to alter ERK1/2 or p38 MAPK phosphorylation. |
| 185 | 11735219 | In the mouse, STAT3, STAT5a, and STAT5b are encoded by adjacent genes on chromosome 11 (60.5 cM). |
| 186 | 11735219 | We identified six known genes and cloned two new genes, termed D11Lgp1 and D11Lgp2. |
| 187 | 11970899 | Attenuation of leptin action and regulation of obesity by protein tyrosine phosphatase 1B. |
| 188 | 11970899 | Mice deficient in protein tyrosine phosphatase 1B (PTP1B) are resistant to diabetes and diet-induced obesity, prompting us to further define the relationship between PTP1B and leptin in modulating obesity. |
| 189 | 11970899 | Leptin-deficient (Lep(ob/ob)) mice lacking PTP1B exhibit an attenuated weight gain, a decrease in adipose tissue, and an increase in resting metabolic rate. |
| 190 | 11970899 | Furthermore, PTP1B-deficient mice show an enhanced response toward leptin-mediated weight loss and suppression of feeding. |
| 191 | 11970899 | Hypothalami from these mice also display markedly increased leptin-induced Stat3 phosphorylation. |
| 192 | 11970899 | Finally, substrate-trapping experiments demonstrate that leptin-activated Jak2, but not Stat3 or the leptin receptor, is a substrate of PTP1B. |
| 193 | 11970899 | These results suggest that PTP1B negatively regulates leptin signaling, and provide one mechanism by which it may regulate obesity. |
| 194 | 11970899 | Attenuation of leptin action and regulation of obesity by protein tyrosine phosphatase 1B. |
| 195 | 11970899 | Mice deficient in protein tyrosine phosphatase 1B (PTP1B) are resistant to diabetes and diet-induced obesity, prompting us to further define the relationship between PTP1B and leptin in modulating obesity. |
| 196 | 11970899 | Leptin-deficient (Lep(ob/ob)) mice lacking PTP1B exhibit an attenuated weight gain, a decrease in adipose tissue, and an increase in resting metabolic rate. |
| 197 | 11970899 | Furthermore, PTP1B-deficient mice show an enhanced response toward leptin-mediated weight loss and suppression of feeding. |
| 198 | 11970899 | Hypothalami from these mice also display markedly increased leptin-induced Stat3 phosphorylation. |
| 199 | 11970899 | Finally, substrate-trapping experiments demonstrate that leptin-activated Jak2, but not Stat3 or the leptin receptor, is a substrate of PTP1B. |
| 200 | 11970899 | These results suggest that PTP1B negatively regulates leptin signaling, and provide one mechanism by which it may regulate obesity. |
| 201 | 12198248 | EMSA showed that SOCS-3 is able to inhibit GH-induced DNA binding of both STAT3 and STAT5 in RIN-5AH cells. |
| 202 | 12424252 | In order to investigate the effects of CNTF on fat cells, we examined the expression of CNTF receptor complex proteins (LIFR, gp130, and CNTFRalpha) during adipocyte differentiation and the effects of CNTF on STAT, Akt, and MAPK activation. |
| 203 | 12424252 | We also examined the ability of CNTF to regulate the expression of adipocyte transcription factors and other adipogenic proteins. |
| 204 | 12424252 | Our studies clearly demonstrate that the expression of two of the three CNTF receptor complex components, CNTFRalpha and LIFR, decreases during adipocyte differentiation. |
| 205 | 12424252 | In addition, preadipocytes are more sensitive to CNTF treatment than adipocytes, as judged by both STAT 3 and Akt activation. |
| 206 | 12424252 | Despite decreased levels of CNTFRalpha expression in fully differentiated 3T3-L1 adipocytes, CNTF treatment of these cells resulted in a time-dependent activation of STAT 3. |
| 207 | 12424252 | Chronic treatment of adipocytes resulted in a substantial decrease in fatty-acid synthase and a notable decline in SREBP-1 levels but had no effect on the expression of peroxisome proliferator-activated receptor gamma, acrp30, adipocyte-expressed STAT proteins, or C/EBPalpha. |
| 208 | 12424252 | Moreover, we demonstrated that CNTF can activate STAT 3 in adipose tissue and skeletal muscle in vivo. |
| 209 | 12424252 | In summary, CNTF affects adipocyte gene expression, and the specific receptor for this cytokine is induced in rodent models of obesity/type II diabetes. |
| 210 | 12424252 | In order to investigate the effects of CNTF on fat cells, we examined the expression of CNTF receptor complex proteins (LIFR, gp130, and CNTFRalpha) during adipocyte differentiation and the effects of CNTF on STAT, Akt, and MAPK activation. |
| 211 | 12424252 | We also examined the ability of CNTF to regulate the expression of adipocyte transcription factors and other adipogenic proteins. |
| 212 | 12424252 | Our studies clearly demonstrate that the expression of two of the three CNTF receptor complex components, CNTFRalpha and LIFR, decreases during adipocyte differentiation. |
| 213 | 12424252 | In addition, preadipocytes are more sensitive to CNTF treatment than adipocytes, as judged by both STAT 3 and Akt activation. |
| 214 | 12424252 | Despite decreased levels of CNTFRalpha expression in fully differentiated 3T3-L1 adipocytes, CNTF treatment of these cells resulted in a time-dependent activation of STAT 3. |
| 215 | 12424252 | Chronic treatment of adipocytes resulted in a substantial decrease in fatty-acid synthase and a notable decline in SREBP-1 levels but had no effect on the expression of peroxisome proliferator-activated receptor gamma, acrp30, adipocyte-expressed STAT proteins, or C/EBPalpha. |
| 216 | 12424252 | Moreover, we demonstrated that CNTF can activate STAT 3 in adipose tissue and skeletal muscle in vivo. |
| 217 | 12424252 | In summary, CNTF affects adipocyte gene expression, and the specific receptor for this cytokine is induced in rodent models of obesity/type II diabetes. |
| 218 | 12424252 | In order to investigate the effects of CNTF on fat cells, we examined the expression of CNTF receptor complex proteins (LIFR, gp130, and CNTFRalpha) during adipocyte differentiation and the effects of CNTF on STAT, Akt, and MAPK activation. |
| 219 | 12424252 | We also examined the ability of CNTF to regulate the expression of adipocyte transcription factors and other adipogenic proteins. |
| 220 | 12424252 | Our studies clearly demonstrate that the expression of two of the three CNTF receptor complex components, CNTFRalpha and LIFR, decreases during adipocyte differentiation. |
| 221 | 12424252 | In addition, preadipocytes are more sensitive to CNTF treatment than adipocytes, as judged by both STAT 3 and Akt activation. |
| 222 | 12424252 | Despite decreased levels of CNTFRalpha expression in fully differentiated 3T3-L1 adipocytes, CNTF treatment of these cells resulted in a time-dependent activation of STAT 3. |
| 223 | 12424252 | Chronic treatment of adipocytes resulted in a substantial decrease in fatty-acid synthase and a notable decline in SREBP-1 levels but had no effect on the expression of peroxisome proliferator-activated receptor gamma, acrp30, adipocyte-expressed STAT proteins, or C/EBPalpha. |
| 224 | 12424252 | Moreover, we demonstrated that CNTF can activate STAT 3 in adipose tissue and skeletal muscle in vivo. |
| 225 | 12424252 | In summary, CNTF affects adipocyte gene expression, and the specific receptor for this cytokine is induced in rodent models of obesity/type II diabetes. |
| 226 | 12453907 | Inhibition of the Jak/STAT signaling pathway prevents the high glucose-induced increase in tgf-beta and fibronectin synthesis in mesangial cells. |
| 227 | 12453907 | We recently found that exposure of cells to HG also activates the growth-promoting enzyme janus kinase 2 (JAK2) and its latent signal transducers and activators of transcription (STAT) transcription factors (STAT1, STAT3, and STAT5). |
| 228 | 12453907 | Our purpose was to determine the effect that inhibition of JAK2 and these STAT transcription factors has on the HG-induced increase in TGF-beta and fibronectin synthesis in GMC. |
| 229 | 12453907 | Exposure of GMC to 25 mmol/l glucose caused the activation of JAK2, STAT1, STAT3, and STAT5 plus an increase in TGF-beta and fibronectin synthesis, as compared with 5.5 mmol/l glucose. |
| 230 | 12453907 | This HG-induced increase in synthesis of TGF-beta and fibronectin was prevented by concomitant incubation with AG-490, a specific JAK2 inhibitor. |
| 231 | 12453907 | The HG-induced JAK2, STAT1, and STAT3 tyrosine phosphorylations in GMC were also abolished by AG-490. |
| 232 | 12453907 | Preincubation of GMC cultured in 25 mmol/l glucose with a specific JAK2 or STAT1 antisense oligonucleotide also prevented both TGF-beta and fibronectin synthesis. |
| 233 | 12453907 | These results provide direct evidence for linkages between JAK2, STAT1, and the glucose-induced overproduction of TGF-beta and fibronectin in GMC. |
| 234 | 12453907 | Inhibition of the Jak/STAT signaling pathway prevents the high glucose-induced increase in tgf-beta and fibronectin synthesis in mesangial cells. |
| 235 | 12453907 | We recently found that exposure of cells to HG also activates the growth-promoting enzyme janus kinase 2 (JAK2) and its latent signal transducers and activators of transcription (STAT) transcription factors (STAT1, STAT3, and STAT5). |
| 236 | 12453907 | Our purpose was to determine the effect that inhibition of JAK2 and these STAT transcription factors has on the HG-induced increase in TGF-beta and fibronectin synthesis in GMC. |
| 237 | 12453907 | Exposure of GMC to 25 mmol/l glucose caused the activation of JAK2, STAT1, STAT3, and STAT5 plus an increase in TGF-beta and fibronectin synthesis, as compared with 5.5 mmol/l glucose. |
| 238 | 12453907 | This HG-induced increase in synthesis of TGF-beta and fibronectin was prevented by concomitant incubation with AG-490, a specific JAK2 inhibitor. |
| 239 | 12453907 | The HG-induced JAK2, STAT1, and STAT3 tyrosine phosphorylations in GMC were also abolished by AG-490. |
| 240 | 12453907 | Preincubation of GMC cultured in 25 mmol/l glucose with a specific JAK2 or STAT1 antisense oligonucleotide also prevented both TGF-beta and fibronectin synthesis. |
| 241 | 12453907 | These results provide direct evidence for linkages between JAK2, STAT1, and the glucose-induced overproduction of TGF-beta and fibronectin in GMC. |
| 242 | 12453907 | Inhibition of the Jak/STAT signaling pathway prevents the high glucose-induced increase in tgf-beta and fibronectin synthesis in mesangial cells. |
| 243 | 12453907 | We recently found that exposure of cells to HG also activates the growth-promoting enzyme janus kinase 2 (JAK2) and its latent signal transducers and activators of transcription (STAT) transcription factors (STAT1, STAT3, and STAT5). |
| 244 | 12453907 | Our purpose was to determine the effect that inhibition of JAK2 and these STAT transcription factors has on the HG-induced increase in TGF-beta and fibronectin synthesis in GMC. |
| 245 | 12453907 | Exposure of GMC to 25 mmol/l glucose caused the activation of JAK2, STAT1, STAT3, and STAT5 plus an increase in TGF-beta and fibronectin synthesis, as compared with 5.5 mmol/l glucose. |
| 246 | 12453907 | This HG-induced increase in synthesis of TGF-beta and fibronectin was prevented by concomitant incubation with AG-490, a specific JAK2 inhibitor. |
| 247 | 12453907 | The HG-induced JAK2, STAT1, and STAT3 tyrosine phosphorylations in GMC were also abolished by AG-490. |
| 248 | 12453907 | Preincubation of GMC cultured in 25 mmol/l glucose with a specific JAK2 or STAT1 antisense oligonucleotide also prevented both TGF-beta and fibronectin synthesis. |
| 249 | 12453907 | These results provide direct evidence for linkages between JAK2, STAT1, and the glucose-induced overproduction of TGF-beta and fibronectin in GMC. |
| 250 | 12456808 | Loss of interleukin 6 results in delayed mammary gland involution: a possible role for mitogen-activated protein kinase and not signal transducer and activator of transcription 3. |
| 251 | 12456808 | This study was based on the hypothesis that IL-6 is the activating cytokine for signal transducer and activator of transcription 3 (Stat), the transcription factor whose presence is required for controlled mammary gland involution. |
| 252 | 12456808 | We now show that expression of IL-6 is low during lactation but increases at the onset of involution in parallel with the activation of Stat3 and p44/42 MAPK. |
| 253 | 12456808 | Moreover, we demonstrated that injection of IL-6 into virgin and lactating mice activates Stat3 in mammary epithelium. |
| 254 | 12456808 | Involution of mammary tissue in IL-6-null mice was delayed similar to that seen in mammary conditional Stat3- and Bax-null mice. |
| 255 | 12456808 | However, Stat3 activation during involution was independent of the IL-6 status. |
| 256 | 12456808 | This suggests that either IL-6 does not induce Stat3 in vivo or its absence is compensated for by other cytokines, such as leukemia-inhibitory factor (LIF). |
| 257 | 12456808 | In contrast, the increase of p44/42 MAPK (ERK1/2) phosphorylation at the onset of involution was dependent on the presence of IL-6. |
| 258 | 12456808 | Delayed involution corresponded with a decrease of epithelial cell death, and a delayed induction of Bax and sulfated glycoprotein 2 (SGP2, or clusterin) expression. |
| 259 | 12456808 | Our experiments demonstrate on a genetic level that IL-6 contributes to the induction of the controlled remodeling of mammary tissue during involution, possibly through the MAPK pathway and by mediating the expression of the cell death protein Bax. |
| 260 | 12456808 | Loss of interleukin 6 results in delayed mammary gland involution: a possible role for mitogen-activated protein kinase and not signal transducer and activator of transcription 3. |
| 261 | 12456808 | This study was based on the hypothesis that IL-6 is the activating cytokine for signal transducer and activator of transcription 3 (Stat), the transcription factor whose presence is required for controlled mammary gland involution. |
| 262 | 12456808 | We now show that expression of IL-6 is low during lactation but increases at the onset of involution in parallel with the activation of Stat3 and p44/42 MAPK. |
| 263 | 12456808 | Moreover, we demonstrated that injection of IL-6 into virgin and lactating mice activates Stat3 in mammary epithelium. |
| 264 | 12456808 | Involution of mammary tissue in IL-6-null mice was delayed similar to that seen in mammary conditional Stat3- and Bax-null mice. |
| 265 | 12456808 | However, Stat3 activation during involution was independent of the IL-6 status. |
| 266 | 12456808 | This suggests that either IL-6 does not induce Stat3 in vivo or its absence is compensated for by other cytokines, such as leukemia-inhibitory factor (LIF). |
| 267 | 12456808 | In contrast, the increase of p44/42 MAPK (ERK1/2) phosphorylation at the onset of involution was dependent on the presence of IL-6. |
| 268 | 12456808 | Delayed involution corresponded with a decrease of epithelial cell death, and a delayed induction of Bax and sulfated glycoprotein 2 (SGP2, or clusterin) expression. |
| 269 | 12456808 | Our experiments demonstrate on a genetic level that IL-6 contributes to the induction of the controlled remodeling of mammary tissue during involution, possibly through the MAPK pathway and by mediating the expression of the cell death protein Bax. |
| 270 | 12456808 | Loss of interleukin 6 results in delayed mammary gland involution: a possible role for mitogen-activated protein kinase and not signal transducer and activator of transcription 3. |
| 271 | 12456808 | This study was based on the hypothesis that IL-6 is the activating cytokine for signal transducer and activator of transcription 3 (Stat), the transcription factor whose presence is required for controlled mammary gland involution. |
| 272 | 12456808 | We now show that expression of IL-6 is low during lactation but increases at the onset of involution in parallel with the activation of Stat3 and p44/42 MAPK. |
| 273 | 12456808 | Moreover, we demonstrated that injection of IL-6 into virgin and lactating mice activates Stat3 in mammary epithelium. |
| 274 | 12456808 | Involution of mammary tissue in IL-6-null mice was delayed similar to that seen in mammary conditional Stat3- and Bax-null mice. |
| 275 | 12456808 | However, Stat3 activation during involution was independent of the IL-6 status. |
| 276 | 12456808 | This suggests that either IL-6 does not induce Stat3 in vivo or its absence is compensated for by other cytokines, such as leukemia-inhibitory factor (LIF). |
| 277 | 12456808 | In contrast, the increase of p44/42 MAPK (ERK1/2) phosphorylation at the onset of involution was dependent on the presence of IL-6. |
| 278 | 12456808 | Delayed involution corresponded with a decrease of epithelial cell death, and a delayed induction of Bax and sulfated glycoprotein 2 (SGP2, or clusterin) expression. |
| 279 | 12456808 | Our experiments demonstrate on a genetic level that IL-6 contributes to the induction of the controlled remodeling of mammary tissue during involution, possibly through the MAPK pathway and by mediating the expression of the cell death protein Bax. |
| 280 | 12456808 | Loss of interleukin 6 results in delayed mammary gland involution: a possible role for mitogen-activated protein kinase and not signal transducer and activator of transcription 3. |
| 281 | 12456808 | This study was based on the hypothesis that IL-6 is the activating cytokine for signal transducer and activator of transcription 3 (Stat), the transcription factor whose presence is required for controlled mammary gland involution. |
| 282 | 12456808 | We now show that expression of IL-6 is low during lactation but increases at the onset of involution in parallel with the activation of Stat3 and p44/42 MAPK. |
| 283 | 12456808 | Moreover, we demonstrated that injection of IL-6 into virgin and lactating mice activates Stat3 in mammary epithelium. |
| 284 | 12456808 | Involution of mammary tissue in IL-6-null mice was delayed similar to that seen in mammary conditional Stat3- and Bax-null mice. |
| 285 | 12456808 | However, Stat3 activation during involution was independent of the IL-6 status. |
| 286 | 12456808 | This suggests that either IL-6 does not induce Stat3 in vivo or its absence is compensated for by other cytokines, such as leukemia-inhibitory factor (LIF). |
| 287 | 12456808 | In contrast, the increase of p44/42 MAPK (ERK1/2) phosphorylation at the onset of involution was dependent on the presence of IL-6. |
| 288 | 12456808 | Delayed involution corresponded with a decrease of epithelial cell death, and a delayed induction of Bax and sulfated glycoprotein 2 (SGP2, or clusterin) expression. |
| 289 | 12456808 | Our experiments demonstrate on a genetic level that IL-6 contributes to the induction of the controlled remodeling of mammary tissue during involution, possibly through the MAPK pathway and by mediating the expression of the cell death protein Bax. |
| 290 | 12456808 | Loss of interleukin 6 results in delayed mammary gland involution: a possible role for mitogen-activated protein kinase and not signal transducer and activator of transcription 3. |
| 291 | 12456808 | This study was based on the hypothesis that IL-6 is the activating cytokine for signal transducer and activator of transcription 3 (Stat), the transcription factor whose presence is required for controlled mammary gland involution. |
| 292 | 12456808 | We now show that expression of IL-6 is low during lactation but increases at the onset of involution in parallel with the activation of Stat3 and p44/42 MAPK. |
| 293 | 12456808 | Moreover, we demonstrated that injection of IL-6 into virgin and lactating mice activates Stat3 in mammary epithelium. |
| 294 | 12456808 | Involution of mammary tissue in IL-6-null mice was delayed similar to that seen in mammary conditional Stat3- and Bax-null mice. |
| 295 | 12456808 | However, Stat3 activation during involution was independent of the IL-6 status. |
| 296 | 12456808 | This suggests that either IL-6 does not induce Stat3 in vivo or its absence is compensated for by other cytokines, such as leukemia-inhibitory factor (LIF). |
| 297 | 12456808 | In contrast, the increase of p44/42 MAPK (ERK1/2) phosphorylation at the onset of involution was dependent on the presence of IL-6. |
| 298 | 12456808 | Delayed involution corresponded with a decrease of epithelial cell death, and a delayed induction of Bax and sulfated glycoprotein 2 (SGP2, or clusterin) expression. |
| 299 | 12456808 | Our experiments demonstrate on a genetic level that IL-6 contributes to the induction of the controlled remodeling of mammary tissue during involution, possibly through the MAPK pathway and by mediating the expression of the cell death protein Bax. |
| 300 | 12456808 | Loss of interleukin 6 results in delayed mammary gland involution: a possible role for mitogen-activated protein kinase and not signal transducer and activator of transcription 3. |
| 301 | 12456808 | This study was based on the hypothesis that IL-6 is the activating cytokine for signal transducer and activator of transcription 3 (Stat), the transcription factor whose presence is required for controlled mammary gland involution. |
| 302 | 12456808 | We now show that expression of IL-6 is low during lactation but increases at the onset of involution in parallel with the activation of Stat3 and p44/42 MAPK. |
| 303 | 12456808 | Moreover, we demonstrated that injection of IL-6 into virgin and lactating mice activates Stat3 in mammary epithelium. |
| 304 | 12456808 | Involution of mammary tissue in IL-6-null mice was delayed similar to that seen in mammary conditional Stat3- and Bax-null mice. |
| 305 | 12456808 | However, Stat3 activation during involution was independent of the IL-6 status. |
| 306 | 12456808 | This suggests that either IL-6 does not induce Stat3 in vivo or its absence is compensated for by other cytokines, such as leukemia-inhibitory factor (LIF). |
| 307 | 12456808 | In contrast, the increase of p44/42 MAPK (ERK1/2) phosphorylation at the onset of involution was dependent on the presence of IL-6. |
| 308 | 12456808 | Delayed involution corresponded with a decrease of epithelial cell death, and a delayed induction of Bax and sulfated glycoprotein 2 (SGP2, or clusterin) expression. |
| 309 | 12456808 | Our experiments demonstrate on a genetic level that IL-6 contributes to the induction of the controlled remodeling of mammary tissue during involution, possibly through the MAPK pathway and by mediating the expression of the cell death protein Bax. |
| 310 | 12456808 | Loss of interleukin 6 results in delayed mammary gland involution: a possible role for mitogen-activated protein kinase and not signal transducer and activator of transcription 3. |
| 311 | 12456808 | This study was based on the hypothesis that IL-6 is the activating cytokine for signal transducer and activator of transcription 3 (Stat), the transcription factor whose presence is required for controlled mammary gland involution. |
| 312 | 12456808 | We now show that expression of IL-6 is low during lactation but increases at the onset of involution in parallel with the activation of Stat3 and p44/42 MAPK. |
| 313 | 12456808 | Moreover, we demonstrated that injection of IL-6 into virgin and lactating mice activates Stat3 in mammary epithelium. |
| 314 | 12456808 | Involution of mammary tissue in IL-6-null mice was delayed similar to that seen in mammary conditional Stat3- and Bax-null mice. |
| 315 | 12456808 | However, Stat3 activation during involution was independent of the IL-6 status. |
| 316 | 12456808 | This suggests that either IL-6 does not induce Stat3 in vivo or its absence is compensated for by other cytokines, such as leukemia-inhibitory factor (LIF). |
| 317 | 12456808 | In contrast, the increase of p44/42 MAPK (ERK1/2) phosphorylation at the onset of involution was dependent on the presence of IL-6. |
| 318 | 12456808 | Delayed involution corresponded with a decrease of epithelial cell death, and a delayed induction of Bax and sulfated glycoprotein 2 (SGP2, or clusterin) expression. |
| 319 | 12456808 | Our experiments demonstrate on a genetic level that IL-6 contributes to the induction of the controlled remodeling of mammary tissue during involution, possibly through the MAPK pathway and by mediating the expression of the cell death protein Bax. |
| 320 | 12540594 | Role of leptin in the regulation of glucagon-like peptide-1 secretion. |
| 321 | 12540594 | Because obesity is linked to abnormal leptin signaling, we hypothesized that leptin may modulate GLP-1 secretion. |
| 322 | 12540594 | Leptin significantly stimulated GLP-1 secretion (by up to 250% of control) from fetal rat intestinal cells, a mouse L cell line (GLUTag), and a human L cell line (NCI-H716) in a dose-dependent manner (P < 0.05-0.001). |
| 323 | 12540594 | The long form of the leptin receptor was shown to be expressed, and leptin induced the phosphorylation of STAT3 in the three cell types. |
| 324 | 12540594 | The leptin receptor was also expressed by rodent and human intestinal L cells, and leptin (1 mg/kg i.p.) significantly stimulated GLP-1 secretion in rats and ob/ob mice. |
| 325 | 12540594 | To determine the effect of leptin resistance on GLP-1 secretion, C57BL/6 mice were fed a high-fat (45%) or low-fat (10%) diet for 8 weeks. |
| 326 | 12540594 | These results show for the first time that leptin stimulates GLP-1 secretion from rodent and human intestinal L cells, and they suggest that leptin resistance may account for the decreased levels of GLP-1 found in obese humans. |
| 327 | 12594516 | STAT3 signalling is required for leptin regulation of energy balance but not reproduction. |
| 328 | 12594516 | Tyr 1138 of LRb mediates activation of the transcription factor STAT3 during leptin action. |
| 329 | 12594516 | To investigate the contribution of STAT3 signalling to leptin action in vivo, we replaced the gene encoding the leptin receptor (lepr) in mice with an allele coding for a replacement of Tyr 1138 in LRb with a serine residue (lepr(S1138)) that specifically disrupts the LRb-STAT3 signal. |
| 330 | 12594516 | LRb-STAT3 signalling thus mediates the effects of leptin on melanocortin production and body energy homeostasis, whereas distinct LRb signals regulate NPY and the control of fertility, growth and glucose homeostasis. |
| 331 | 12594516 | STAT3 signalling is required for leptin regulation of energy balance but not reproduction. |
| 332 | 12594516 | Tyr 1138 of LRb mediates activation of the transcription factor STAT3 during leptin action. |
| 333 | 12594516 | To investigate the contribution of STAT3 signalling to leptin action in vivo, we replaced the gene encoding the leptin receptor (lepr) in mice with an allele coding for a replacement of Tyr 1138 in LRb with a serine residue (lepr(S1138)) that specifically disrupts the LRb-STAT3 signal. |
| 334 | 12594516 | LRb-STAT3 signalling thus mediates the effects of leptin on melanocortin production and body energy homeostasis, whereas distinct LRb signals regulate NPY and the control of fertility, growth and glucose homeostasis. |
| 335 | 12594516 | STAT3 signalling is required for leptin regulation of energy balance but not reproduction. |
| 336 | 12594516 | Tyr 1138 of LRb mediates activation of the transcription factor STAT3 during leptin action. |
| 337 | 12594516 | To investigate the contribution of STAT3 signalling to leptin action in vivo, we replaced the gene encoding the leptin receptor (lepr) in mice with an allele coding for a replacement of Tyr 1138 in LRb with a serine residue (lepr(S1138)) that specifically disrupts the LRb-STAT3 signal. |
| 338 | 12594516 | LRb-STAT3 signalling thus mediates the effects of leptin on melanocortin production and body energy homeostasis, whereas distinct LRb signals regulate NPY and the control of fertility, growth and glucose homeostasis. |
| 339 | 12594516 | STAT3 signalling is required for leptin regulation of energy balance but not reproduction. |
| 340 | 12594516 | Tyr 1138 of LRb mediates activation of the transcription factor STAT3 during leptin action. |
| 341 | 12594516 | To investigate the contribution of STAT3 signalling to leptin action in vivo, we replaced the gene encoding the leptin receptor (lepr) in mice with an allele coding for a replacement of Tyr 1138 in LRb with a serine residue (lepr(S1138)) that specifically disrupts the LRb-STAT3 signal. |
| 342 | 12594516 | LRb-STAT3 signalling thus mediates the effects of leptin on melanocortin production and body energy homeostasis, whereas distinct LRb signals regulate NPY and the control of fertility, growth and glucose homeostasis. |
| 343 | 12847226 | Thyrotropin-mediated repression of class II trans-activator expression in thyroid cells: involvement of STAT3 and suppressor of cytokine signaling. |
| 344 | 12847226 | Thyrotropin (TSH) represses IFN-gamma-induced CIITA expression by inhibiting type IV CIITA promoter activity through the suppression of STAT1 activation and IFN regulatory factor 1 induction. |
| 345 | 12847226 | This study found that TSH induces transcriptional activation of the STAT3 gene through the phosphorylation of STAT3 and CREB activation. |
| 346 | 12847226 | TSH induces SOCS-1 and SOCS-3, and TSH-mediated SOCS-3 induction was dependent on STAT3. |
| 347 | 12847226 | The cell line stably expressing the wild-type STAT3 showed a higher CIITA induction in response to IFN-gamma and also exhibited TSH repression of the IFN-gamma-mediated induction of CIITA. |
| 348 | 12847226 | However, TSH repression of the IFN-gamma-induced CIITA expression was not observed in FRTL-5 thyroid cells, which stably expresses the dominant negative forms of STAT3, STAT3-Y705F, and STAT3-S727A. |
| 349 | 12847226 | Thyrotropin-mediated repression of class II trans-activator expression in thyroid cells: involvement of STAT3 and suppressor of cytokine signaling. |
| 350 | 12847226 | Thyrotropin (TSH) represses IFN-gamma-induced CIITA expression by inhibiting type IV CIITA promoter activity through the suppression of STAT1 activation and IFN regulatory factor 1 induction. |
| 351 | 12847226 | This study found that TSH induces transcriptional activation of the STAT3 gene through the phosphorylation of STAT3 and CREB activation. |
| 352 | 12847226 | TSH induces SOCS-1 and SOCS-3, and TSH-mediated SOCS-3 induction was dependent on STAT3. |
| 353 | 12847226 | The cell line stably expressing the wild-type STAT3 showed a higher CIITA induction in response to IFN-gamma and also exhibited TSH repression of the IFN-gamma-mediated induction of CIITA. |
| 354 | 12847226 | However, TSH repression of the IFN-gamma-induced CIITA expression was not observed in FRTL-5 thyroid cells, which stably expresses the dominant negative forms of STAT3, STAT3-Y705F, and STAT3-S727A. |
| 355 | 12847226 | Thyrotropin-mediated repression of class II trans-activator expression in thyroid cells: involvement of STAT3 and suppressor of cytokine signaling. |
| 356 | 12847226 | Thyrotropin (TSH) represses IFN-gamma-induced CIITA expression by inhibiting type IV CIITA promoter activity through the suppression of STAT1 activation and IFN regulatory factor 1 induction. |
| 357 | 12847226 | This study found that TSH induces transcriptional activation of the STAT3 gene through the phosphorylation of STAT3 and CREB activation. |
| 358 | 12847226 | TSH induces SOCS-1 and SOCS-3, and TSH-mediated SOCS-3 induction was dependent on STAT3. |
| 359 | 12847226 | The cell line stably expressing the wild-type STAT3 showed a higher CIITA induction in response to IFN-gamma and also exhibited TSH repression of the IFN-gamma-mediated induction of CIITA. |
| 360 | 12847226 | However, TSH repression of the IFN-gamma-induced CIITA expression was not observed in FRTL-5 thyroid cells, which stably expresses the dominant negative forms of STAT3, STAT3-Y705F, and STAT3-S727A. |
| 361 | 12847226 | Thyrotropin-mediated repression of class II trans-activator expression in thyroid cells: involvement of STAT3 and suppressor of cytokine signaling. |
| 362 | 12847226 | Thyrotropin (TSH) represses IFN-gamma-induced CIITA expression by inhibiting type IV CIITA promoter activity through the suppression of STAT1 activation and IFN regulatory factor 1 induction. |
| 363 | 12847226 | This study found that TSH induces transcriptional activation of the STAT3 gene through the phosphorylation of STAT3 and CREB activation. |
| 364 | 12847226 | TSH induces SOCS-1 and SOCS-3, and TSH-mediated SOCS-3 induction was dependent on STAT3. |
| 365 | 12847226 | The cell line stably expressing the wild-type STAT3 showed a higher CIITA induction in response to IFN-gamma and also exhibited TSH repression of the IFN-gamma-mediated induction of CIITA. |
| 366 | 12847226 | However, TSH repression of the IFN-gamma-induced CIITA expression was not observed in FRTL-5 thyroid cells, which stably expresses the dominant negative forms of STAT3, STAT3-Y705F, and STAT3-S727A. |
| 367 | 12847226 | Thyrotropin-mediated repression of class II trans-activator expression in thyroid cells: involvement of STAT3 and suppressor of cytokine signaling. |
| 368 | 12847226 | Thyrotropin (TSH) represses IFN-gamma-induced CIITA expression by inhibiting type IV CIITA promoter activity through the suppression of STAT1 activation and IFN regulatory factor 1 induction. |
| 369 | 12847226 | This study found that TSH induces transcriptional activation of the STAT3 gene through the phosphorylation of STAT3 and CREB activation. |
| 370 | 12847226 | TSH induces SOCS-1 and SOCS-3, and TSH-mediated SOCS-3 induction was dependent on STAT3. |
| 371 | 12847226 | The cell line stably expressing the wild-type STAT3 showed a higher CIITA induction in response to IFN-gamma and also exhibited TSH repression of the IFN-gamma-mediated induction of CIITA. |
| 372 | 12847226 | However, TSH repression of the IFN-gamma-induced CIITA expression was not observed in FRTL-5 thyroid cells, which stably expresses the dominant negative forms of STAT3, STAT3-Y705F, and STAT3-S727A. |
| 373 | 12921973 | Leptin induces angiogenesis by its proliferative effects on endothelial cells (ECs) via OB receptor (OB-Rb) gene. |
| 374 | 12921973 | Leptin induced phosphorylation of Janus kinase (JAK)2, signal transducer and activator of transcription (STAT)3, and extracellular signal-regulated kinase (ERK) in ECs from ZL rats but not ZF rats. |
| 375 | 12921973 | Infection with Ad.OB-Rb restored phosphorylation of JAK2 and STAT3 in ECs from ZF rats. |
| 376 | 12921973 | Leptin induces angiogenesis by its proliferative effects on endothelial cells (ECs) via OB receptor (OB-Rb) gene. |
| 377 | 12921973 | Leptin induced phosphorylation of Janus kinase (JAK)2, signal transducer and activator of transcription (STAT)3, and extracellular signal-regulated kinase (ERK) in ECs from ZL rats but not ZF rats. |
| 378 | 12921973 | Infection with Ad.OB-Rb restored phosphorylation of JAK2 and STAT3 in ECs from ZF rats. |
| 379 | 14557860 | The role of leptin-->STAT3 signaling in neuroendocrine function: an integrative perspective. |
| 380 | 14578297 | Chronic exposure to interleukin-6 causes hepatic insulin resistance in mice. |
| 381 | 14578297 | Interleukin (IL)-6 is one of several proinflammatory cytokines associated with the insulin resistance of obesity and type 2 diabetes. |
| 382 | 14578297 | There is, however, little direct evidence in vivo for a causative role of IL-6 in insulin resistance. |
| 383 | 14578297 | Here, a 5-day constant subcutaneous infusion of hIL-6 before portal vein insulin challenge resulted in impairment of early insulin receptor signaling in the liver of mice. |
| 384 | 14578297 | Consistent with an hepatic response to IL-6, STAT3 phosphorylation was increased in livers of IL-6-treated mice at 5 days. |
| 385 | 14578297 | Chronic infusion of IL-6 also reduced hepatic insulin receptor autophosphorylation by 60% and tyrosine phosphorylation of insulin receptor substrates-1 and -2 by 60 and 40%, respectively. |
| 386 | 14578297 | IL-6 also decreased refeeding-dependent glucokinase mRNA induction by approximately 40%. |
| 387 | 14578297 | In contrast to hepatic insulin receptor signal transduction, 5-day IL-6 exposure failed to suppress skeletal muscle insulin receptor signal transduction. |
| 388 | 14578297 | These data suggest that chronic IL-6 treatment selectively impairs hepatic insulin signaling in vivo, further supporting a role for IL-6 in hepatic insulin resistance of obesity. |
| 389 | 14643059 | Here, we review the mechanisms by which leptin activates intracellular signaling and the roles of two specific leptin-activated signals [phosphatidylinositol 3-kinase and signal transducer and activator of transcription-3 (STAT3)] in the regulation of body weight and neuroendocrine function. |
| 390 | 14643059 | The pathway by which leptin activates STAT3 is particularly intriguing because it is crucial for the regulation of feeding but dispensable for the control of reproductive and growth axes. |
| 391 | 14643059 | Here, we review the mechanisms by which leptin activates intracellular signaling and the roles of two specific leptin-activated signals [phosphatidylinositol 3-kinase and signal transducer and activator of transcription-3 (STAT3)] in the regulation of body weight and neuroendocrine function. |
| 392 | 14643059 | The pathway by which leptin activates STAT3 is particularly intriguing because it is crucial for the regulation of feeding but dispensable for the control of reproductive and growth axes. |
| 393 | 14673160 | To that end, STAT3(lox/lox) mice were crossed with mice expressing Cre under the control of rat insulin II gene promoter (RIP-Cre mice). |
| 394 | 14673160 | Double immunohistochemical staining confirmed that deletion of STAT3 occurred in leptin receptor (OB-Rb isoform)-positive neurons. |
| 395 | 14673160 | Body weight, body fat, and mRNA and protein levels of leptin are all significantly increased in RIP-Cre/STAT3(lox/lox) mice. |
| 396 | 14673160 | Administration of recombinant leptin by intracerebroventricular infusion failed to cause complete loss of body fat in RIP-Cre/STAT3(lox/lox) mice. |
| 397 | 14673160 | To that end, STAT3(lox/lox) mice were crossed with mice expressing Cre under the control of rat insulin II gene promoter (RIP-Cre mice). |
| 398 | 14673160 | Double immunohistochemical staining confirmed that deletion of STAT3 occurred in leptin receptor (OB-Rb isoform)-positive neurons. |
| 399 | 14673160 | Body weight, body fat, and mRNA and protein levels of leptin are all significantly increased in RIP-Cre/STAT3(lox/lox) mice. |
| 400 | 14673160 | Administration of recombinant leptin by intracerebroventricular infusion failed to cause complete loss of body fat in RIP-Cre/STAT3(lox/lox) mice. |
| 401 | 14673160 | To that end, STAT3(lox/lox) mice were crossed with mice expressing Cre under the control of rat insulin II gene promoter (RIP-Cre mice). |
| 402 | 14673160 | Double immunohistochemical staining confirmed that deletion of STAT3 occurred in leptin receptor (OB-Rb isoform)-positive neurons. |
| 403 | 14673160 | Body weight, body fat, and mRNA and protein levels of leptin are all significantly increased in RIP-Cre/STAT3(lox/lox) mice. |
| 404 | 14673160 | Administration of recombinant leptin by intracerebroventricular infusion failed to cause complete loss of body fat in RIP-Cre/STAT3(lox/lox) mice. |
| 405 | 14673160 | To that end, STAT3(lox/lox) mice were crossed with mice expressing Cre under the control of rat insulin II gene promoter (RIP-Cre mice). |
| 406 | 14673160 | Double immunohistochemical staining confirmed that deletion of STAT3 occurred in leptin receptor (OB-Rb isoform)-positive neurons. |
| 407 | 14673160 | Body weight, body fat, and mRNA and protein levels of leptin are all significantly increased in RIP-Cre/STAT3(lox/lox) mice. |
| 408 | 14673160 | Administration of recombinant leptin by intracerebroventricular infusion failed to cause complete loss of body fat in RIP-Cre/STAT3(lox/lox) mice. |
| 409 | 14678947 | Angiotensin II blockade prevents hyperglycemia-induced activation of JAK and STAT proteins in diabetic rat kidney glomeruli. |
| 410 | 14678947 | Clinical and animal studies show that treatment with angiotensin-converting enzyme (ACE) inhibitors or ANG II-receptor antagonists slows progression of nephropathy in diabetes, indicating ANG II plays an important role in its development. |
| 411 | 14678947 | We previously reported that hyperglycemia augments both ANG II-induced growth and activation of Janus kinase (JAK)2 and signal transducers and activators of transcription (STAT) proteins in cultured rat mesangial cells. |
| 412 | 14678947 | Furthermore, we demonstrated that the tyrosine kinase enzyme JAK2 plays a key role in both ANG II- and hyperglycemia-induced growth in these cells. |
| 413 | 14678947 | We hypothesized that the ACE inhibitor captopril and the ANG II-receptor antagonist candesartan would hinder hyperglycemic-induced activation of JAK and STAT proteins in rat glomeruli, demonstrating that ANG II plays an important role in the activation of these proteins in vivo. |
| 414 | 14678947 | STZ stimulated glomerular phosphorylation of JAK2, STAT1, STAT3, and STAT5. |
| 415 | 14678947 | In conclusion, our studies demonstrate that hyperglycemia induces activation of JAK2 and the STATs in vivo via an ANG II-dependent mechanism and that these proteins may be involved in the early kidney damage associated with diabetes. |
| 416 | 14716305 | Here we show that mice with liver-specific deficiency in STAT-3, achieved using the Cre-loxP system, show insulin resistance associated with increased hepatic expression of gluconeogenic genes. |
| 417 | 14716305 | Overexpression of STAT-3 in cultured hepatocytes inhibited gluconeogenic gene expression independently of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha), an upstream regulator of gluconeogenic genes. |
| 418 | 14716305 | Liver-specific expression of a constitutively active form of STAT-3, achieved by infection with an adenovirus vector, markedly reduced blood glucose, plasma insulin concentrations and hepatic gluconeogenic gene expression in diabetic mice. |
| 419 | 14716305 | Here we show that mice with liver-specific deficiency in STAT-3, achieved using the Cre-loxP system, show insulin resistance associated with increased hepatic expression of gluconeogenic genes. |
| 420 | 14716305 | Overexpression of STAT-3 in cultured hepatocytes inhibited gluconeogenic gene expression independently of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha), an upstream regulator of gluconeogenic genes. |
| 421 | 14716305 | Liver-specific expression of a constitutively active form of STAT-3, achieved by infection with an adenovirus vector, markedly reduced blood glucose, plasma insulin concentrations and hepatic gluconeogenic gene expression in diabetic mice. |
| 422 | 14716305 | Here we show that mice with liver-specific deficiency in STAT-3, achieved using the Cre-loxP system, show insulin resistance associated with increased hepatic expression of gluconeogenic genes. |
| 423 | 14716305 | Overexpression of STAT-3 in cultured hepatocytes inhibited gluconeogenic gene expression independently of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha), an upstream regulator of gluconeogenic genes. |
| 424 | 14716305 | Liver-specific expression of a constitutively active form of STAT-3, achieved by infection with an adenovirus vector, markedly reduced blood glucose, plasma insulin concentrations and hepatic gluconeogenic gene expression in diabetic mice. |
| 425 | 14749507 | LRb initiates signaling via three major mechanisms: 1) Tyr(985) of LRb recruits SH2-containing tyrosine phosphatase (SHP-2); 2) Tyr(1138) of LRb recruits signal transducer and activator of transcription 3 (STAT3); and 3) tyrosine phosphorylation sites on the receptor-associated Jak2 likely recruit numerous undefined signaling proteins. |
| 426 | 14749507 | The Tyr(985) --> SHP-2 pathway is a major regulator of extracellular signal-regulated kinase (ERK) activation during leptin signaling in cultured cells, while the Tyr(1138) --> STAT3 pathway induces the feedback inhibitor, suppressor of cytokine signaling 3 (SOCS3), as well as important positive effectors of leptin action. |
| 427 | 14749507 | The Jak2-dependent activation of the insulin receptor substrate (IRS) protein --> phosphatidylinositol 3-kinase (PI3'-K) pathway appears to regulate membrane potential in LRb-expressing neurons and contributes to the regulation of feeding. |
| 428 | 14749507 | Interestingly, the Tyr(1138) --> STAT3 pathway does not strongly regulate neuropeptide Y (NPY) and thus is not required for the control of reproduction and growth. |
| 429 | 14749507 | LRb initiates signaling via three major mechanisms: 1) Tyr(985) of LRb recruits SH2-containing tyrosine phosphatase (SHP-2); 2) Tyr(1138) of LRb recruits signal transducer and activator of transcription 3 (STAT3); and 3) tyrosine phosphorylation sites on the receptor-associated Jak2 likely recruit numerous undefined signaling proteins. |
| 430 | 14749507 | The Tyr(985) --> SHP-2 pathway is a major regulator of extracellular signal-regulated kinase (ERK) activation during leptin signaling in cultured cells, while the Tyr(1138) --> STAT3 pathway induces the feedback inhibitor, suppressor of cytokine signaling 3 (SOCS3), as well as important positive effectors of leptin action. |
| 431 | 14749507 | The Jak2-dependent activation of the insulin receptor substrate (IRS) protein --> phosphatidylinositol 3-kinase (PI3'-K) pathway appears to regulate membrane potential in LRb-expressing neurons and contributes to the regulation of feeding. |
| 432 | 14749507 | Interestingly, the Tyr(1138) --> STAT3 pathway does not strongly regulate neuropeptide Y (NPY) and thus is not required for the control of reproduction and growth. |
| 433 | 14749507 | LRb initiates signaling via three major mechanisms: 1) Tyr(985) of LRb recruits SH2-containing tyrosine phosphatase (SHP-2); 2) Tyr(1138) of LRb recruits signal transducer and activator of transcription 3 (STAT3); and 3) tyrosine phosphorylation sites on the receptor-associated Jak2 likely recruit numerous undefined signaling proteins. |
| 434 | 14749507 | The Tyr(985) --> SHP-2 pathway is a major regulator of extracellular signal-regulated kinase (ERK) activation during leptin signaling in cultured cells, while the Tyr(1138) --> STAT3 pathway induces the feedback inhibitor, suppressor of cytokine signaling 3 (SOCS3), as well as important positive effectors of leptin action. |
| 435 | 14749507 | The Jak2-dependent activation of the insulin receptor substrate (IRS) protein --> phosphatidylinositol 3-kinase (PI3'-K) pathway appears to regulate membrane potential in LRb-expressing neurons and contributes to the regulation of feeding. |
| 436 | 14749507 | Interestingly, the Tyr(1138) --> STAT3 pathway does not strongly regulate neuropeptide Y (NPY) and thus is not required for the control of reproduction and growth. |
| 437 | 15070774 | Signal transducer and activator of transcription (STAT)3 is widely expressed in the CNS during development and adulthood. |
| 438 | 15070774 | STAT3 has been implicated in the control of neuron/glial differentiation and leptin-mediated energy homeostasis, but the physiological role and degree of involvement of STAT3 in these processes is not defined and controversial because of the lack of a direct genetic model. |
| 439 | 15070774 | Administering a melanocortin-3/4 receptor agonist abrogated the hyperphagia and hypothalamic immunohistochemistry showed a marked reduction in proopiomelanocortin with an increase in neuropeptide Y and agouti-related protein. |
| 440 | 15070774 | STAT3(N-/-) mice are hyperleptinemic, suggesting a leptin-resistant condition. |
| 441 | 15070774 | Signal transducer and activator of transcription (STAT)3 is widely expressed in the CNS during development and adulthood. |
| 442 | 15070774 | STAT3 has been implicated in the control of neuron/glial differentiation and leptin-mediated energy homeostasis, but the physiological role and degree of involvement of STAT3 in these processes is not defined and controversial because of the lack of a direct genetic model. |
| 443 | 15070774 | Administering a melanocortin-3/4 receptor agonist abrogated the hyperphagia and hypothalamic immunohistochemistry showed a marked reduction in proopiomelanocortin with an increase in neuropeptide Y and agouti-related protein. |
| 444 | 15070774 | STAT3(N-/-) mice are hyperleptinemic, suggesting a leptin-resistant condition. |
| 445 | 15070774 | Signal transducer and activator of transcription (STAT)3 is widely expressed in the CNS during development and adulthood. |
| 446 | 15070774 | STAT3 has been implicated in the control of neuron/glial differentiation and leptin-mediated energy homeostasis, but the physiological role and degree of involvement of STAT3 in these processes is not defined and controversial because of the lack of a direct genetic model. |
| 447 | 15070774 | Administering a melanocortin-3/4 receptor agonist abrogated the hyperphagia and hypothalamic immunohistochemistry showed a marked reduction in proopiomelanocortin with an increase in neuropeptide Y and agouti-related protein. |
| 448 | 15070774 | STAT3(N-/-) mice are hyperleptinemic, suggesting a leptin-resistant condition. |
| 449 | 15077188 | In contrast, the monomeric and cytoplasmic mutant Y705F induces a constitutive invasive phenotype through Wnt/Rho-independent and EGFR/PI3-kinase-dependent pathways. |
| 450 | 15077188 | STAT3-Y705F-transfected HCT8/S11 cells display an increased tyrosine phosphorylation of the cell-cell adhesion regulator beta-catenin and its dissociation from the invasion suppressor E-cadherin at cell-cell contacts. |
| 451 | 15077188 | Disruption of this cascade by Y705F reveals the proinvasive potential of altered forms of STAT3 as a persistent signaling adaptor in cytokine/transforming growth factor receptor scaffolds and oncogenic pathways. |
| 452 | 15077188 | In contrast, the monomeric and cytoplasmic mutant Y705F induces a constitutive invasive phenotype through Wnt/Rho-independent and EGFR/PI3-kinase-dependent pathways. |
| 453 | 15077188 | STAT3-Y705F-transfected HCT8/S11 cells display an increased tyrosine phosphorylation of the cell-cell adhesion regulator beta-catenin and its dissociation from the invasion suppressor E-cadherin at cell-cell contacts. |
| 454 | 15077188 | Disruption of this cascade by Y705F reveals the proinvasive potential of altered forms of STAT3 as a persistent signaling adaptor in cytokine/transforming growth factor receptor scaffolds and oncogenic pathways. |
| 455 | 15240880 | Here we show that overexpression of suppressors of cytokine signaling (SOCS)-1 and SOCS-3 in liver causes insulin resistance and an increase in the key regulator of fatty acid synthesis in liver, sterol regulatory element-binding protein (SREBP)-1c. |
| 456 | 15240880 | Conversely, inhibition of SOCS-1 and -3 in obese diabetic mice improves insulin sensitivity, normalizes the increased expression of SREBP-1c, and dramatically ameliorates hepatic steatosis and hypertriglyceridemia. |
| 457 | 15240880 | In obese animals, increased SOCS proteins enhance SREBP-1c expression by antagonizing STAT3-mediated inhibition of SREBP-1c promoter activity. |
| 458 | 15240880 | Thus, SOCS proteins play an important role in pathogenesis of the metabolic syndrome by concordantly modulating insulin signaling and cytokine signaling. |
| 459 | 15277698 | The preservation of "stemness" in mouse embryonic stem (mES) cells is maintained through a signal transduction pathway that requires the gp130 receptor, the interleukin-6 (IL-6) family of cytokines, and the Janus Kinase-signal transducer and activator (JAK/STAT) pathway. |
| 460 | 15277698 | Human ES cells differentiate in the presence of members of the IL-6 family of cytokines including leukemia inhibitory factor (LIF) and IL-6 or in the presence of the designer cytokine hyper-IL-6, which is a complex of soluble interleukin-6 receptor (IL-6R) and IL-6 with greatly enhanced bioactivity. |
| 461 | 15277698 | Human ES cells express LIF, IL-6, and gp130 receptors, as well as the downstream signaling molecules. |
| 462 | 15277698 | Stimulation of human and mouse ES cells with gp130 cytokines resulted in a robust phosphorylation of downstream ERK1, ERK2, and Akt kinases, as well as the STAT3 transcription factor. |
| 463 | 15277698 | Loss of the pluripotency markers Nanog, Oct-4, and TRA-1-60 was observed in hES cells during gp130-dependent signaling, indicating that signaling through this pathway is insufficient to prevent the onset of differentiation. |
| 464 | 15331557 | Leptin stimulates ischemia-induced retinal neovascularization: possible role of vascular endothelial growth factor expressed in retinal endothelial cells. |
| 465 | 15331557 | Leptin receptor expression was also detected in primary cultures of porcine retinal endothelial cells, where it upregulated vascular endothelial growth factor (VEGF) mRNA expression. |
| 466 | 15331557 | This effect was thought to be mediated at least partly through the activation of signal transducers and activators of transcription (STAT)3, because adenoviral transfection of the dominant-negative form of STAT3 abolished the leptin-induced upregulation of VEGF mRNA expression in retinal endothelial cells. |
| 467 | 15331557 | This study provides evidence that leptin stimulates the ischemia-induced retinal neovasucularization possibly through the upregulation of endothelial VEGF, thereby suggesting that leptin antagonism may offer a novel therapeutic strategy to prevent or treat diabetic retinopathy. |
| 468 | 15389315 | In the same construct, we have also inserted loxP sites that flank Lepr coding exon 17, a region that encodes a JAK docking site required for STAT3 signaling. |
| 469 | 15561935 | Thus, the LRb-->STAT3 signal is central to both the control of energy expenditure by leptin and the neuroendocrine regulation of the SNS and the thyroid axis. |
| 470 | 15601754 | Previous studies have shown the presence of 5-HT2A, 5-HT2B, and 5-HT1B receptors in vascular smooth muscle cells (VSMCs). |
| 471 | 15601754 | There are currently no data regarding 5-HT2B and 5-HT1B receptor activation of the JAK/STAT pathway in VSMCs and resultant potential alterations in 5-HT signaling in diabetes. |
| 472 | 15601754 | Therefore, we tested the hypothesis that 5-HT differentially activates the JAK/STAT pathway in VSMCs under conditions of normal (5 mM) and high (25 mM) glucose. |
| 473 | 15601754 | Treatment of rat VSMCs with 5-HT (10(-6) M) resulted in time-dependent activation ( approximately 2-fold) of JAK2, JAK1, and STAT1, but not STAT3 (maximal at 5 min, returned to baseline by 30 min). |
| 474 | 15601754 | The 5-HT2B receptor agonist BW723C86 and the 5-HT1B receptor agonist CGS12066A (10(-9)-10(-5) M, 5-min stimulation) did not activate the JAK/STAT pathway. |
| 475 | 15601754 | Treatment with the 5-HT2A receptor antagonist ketanserin (10 nM) inhibited JAK2 activation by 5-HT. |
| 476 | 15601754 | Treatment of streptozotocin-induced diabetic rats with ketanserin (5 mg.kg-1.day-1) reduced activation of JAK2 and STAT1 but not STAT3 in endothelium-denuded thoracic aorta in vivo. 5-HT (10(-6) M) treatment resulted in increased cell proliferation and increased DNA synthesis, which were inhibited by the JAK2 inhibitor AG490. |
| 477 | 15601754 | Further studies with apocynin, diphenyleneiodonium chloride, catalase, and virally transfected superoxide dismutase had no effect at either glucose concentration on activation of the JAK/STAT pathway by 5-HT. |
| 478 | 15601754 | Therefore, we conclude that 5-HT activates JAK2, JAK1, and STAT1 via the 5-HT2A receptors in a reactive oxygen species-independent manner under both normal and high glucose conditions. |
| 479 | 15601754 | Previous studies have shown the presence of 5-HT2A, 5-HT2B, and 5-HT1B receptors in vascular smooth muscle cells (VSMCs). |
| 480 | 15601754 | There are currently no data regarding 5-HT2B and 5-HT1B receptor activation of the JAK/STAT pathway in VSMCs and resultant potential alterations in 5-HT signaling in diabetes. |
| 481 | 15601754 | Therefore, we tested the hypothesis that 5-HT differentially activates the JAK/STAT pathway in VSMCs under conditions of normal (5 mM) and high (25 mM) glucose. |
| 482 | 15601754 | Treatment of rat VSMCs with 5-HT (10(-6) M) resulted in time-dependent activation ( approximately 2-fold) of JAK2, JAK1, and STAT1, but not STAT3 (maximal at 5 min, returned to baseline by 30 min). |
| 483 | 15601754 | The 5-HT2B receptor agonist BW723C86 and the 5-HT1B receptor agonist CGS12066A (10(-9)-10(-5) M, 5-min stimulation) did not activate the JAK/STAT pathway. |
| 484 | 15601754 | Treatment with the 5-HT2A receptor antagonist ketanserin (10 nM) inhibited JAK2 activation by 5-HT. |
| 485 | 15601754 | Treatment of streptozotocin-induced diabetic rats with ketanserin (5 mg.kg-1.day-1) reduced activation of JAK2 and STAT1 but not STAT3 in endothelium-denuded thoracic aorta in vivo. 5-HT (10(-6) M) treatment resulted in increased cell proliferation and increased DNA synthesis, which were inhibited by the JAK2 inhibitor AG490. |
| 486 | 15601754 | Further studies with apocynin, diphenyleneiodonium chloride, catalase, and virally transfected superoxide dismutase had no effect at either glucose concentration on activation of the JAK/STAT pathway by 5-HT. |
| 487 | 15601754 | Therefore, we conclude that 5-HT activates JAK2, JAK1, and STAT1 via the 5-HT2A receptors in a reactive oxygen species-independent manner under both normal and high glucose conditions. |
| 488 | 15604114 | Feedback inhibition of leptin receptor/Jak2 signaling via Tyr1138 of the leptin receptor and suppressor of cytokine signaling 3. |
| 489 | 15604114 | Using cultured cells exogenously expressing the long form of the leptin receptor (LRb) or an erythropoietin receptor/LRb chimera, we show that chronic stimulation results in the attenuation of LRb signaling and the establishment of a state in which the receptor is refractory to reactivation. |
| 490 | 15604114 | Mutation of LRb Tyr1138 (the site that recruits signal transducer and activator of transcription 3) alleviated this feedback inhibition, suggesting that signal transducer and activator of transcription 3 mediates the induction of a feedback inhibitor, such as suppressor of cytokine signaling 3 (SOCS3), during chronic LRb stimulation. |
| 491 | 15613409 | Recombinant methionyl human leptin administration activates signal transducer and activator of transcription 3 signaling in peripheral blood mononuclear cells in vivo and regulates soluble tumor necrosis factor-alpha receptor levels in humans with relative leptin deficiency. |
| 492 | 15662590 | TSH failed to induce either the adenylate cyclase/cAMP pathway, the phosphatidylinositol/calcium pathway, or the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) 3 pathway. |
| 493 | 15662590 | We report that TtT/GF cells express a functional TSHR that is not coupled to cAMP nor IP (3) but probably signals through the JAK/STAT5a pathway. |
| 494 | 15749807 | Prolonged insulin treatment inhibits GH signaling via STAT3 and STAT1. |
| 495 | 15749807 | Previous studies in our laboratory have shown that GH induction of signal transducers and activators of transcription (STAT)5B tyrosine phosphorylation is inhibited by prolonged insulin treatment, probably via downregulation of GHR. |
| 496 | 15749807 | Here, we find that in rat H4IIE hepatoma cells GH-induced tyrosine phosphorylation of two other STATs (STAT3 and STAT1) was also greatly reduced following prolonged insulin pretreatment compared with that induced by GH alone. |
| 497 | 15749807 | In the present work, total STAT5B and STAT1 protein levels were not altered by prolonged insulin treatment. |
| 498 | 15749807 | However, prolonged insulin treatment (16 h; 10 or 100 nM) resulted in a 30-40% reduction of total STAT3 protein, with little change at 0.1 and 1.0 nM insulin. |
| 499 | 15749807 | Thus, there is a selective reduction of total STAT3 protein levels by insulin, but only at high concentration of insulin. |
| 500 | 15749807 | Basal tyrosine phosphorylated (PY)-STAT3 was also significantly reduced by prolonged insulin treatment, and to a greater extent than total STAT3 protein levels. |
| 501 | 15749807 | The inhibitory effect of insulin on total STAT3 protein and basal PY-STAT3 levels was dependent on activation of the MEK-ERK pathway, rather than the PI3K pathway. |
| 502 | 15749807 | In contrast, the MEK-ERK pathway did not play a major role in insulin's inhibition of GH-induced PY-STAT3 and PY-STAT1. |
| 503 | 15749807 | The present studies indicate that prolonged hyperinsulinemia, such as that found in some obese patients or patients with Type 2 diabetes mellitus, may have profound effects on GH signaling via STAT3 and STAT1. |
| 504 | 15749807 | Prolonged insulin treatment inhibits GH signaling via STAT3 and STAT1. |
| 505 | 15749807 | Previous studies in our laboratory have shown that GH induction of signal transducers and activators of transcription (STAT)5B tyrosine phosphorylation is inhibited by prolonged insulin treatment, probably via downregulation of GHR. |
| 506 | 15749807 | Here, we find that in rat H4IIE hepatoma cells GH-induced tyrosine phosphorylation of two other STATs (STAT3 and STAT1) was also greatly reduced following prolonged insulin pretreatment compared with that induced by GH alone. |
| 507 | 15749807 | In the present work, total STAT5B and STAT1 protein levels were not altered by prolonged insulin treatment. |
| 508 | 15749807 | However, prolonged insulin treatment (16 h; 10 or 100 nM) resulted in a 30-40% reduction of total STAT3 protein, with little change at 0.1 and 1.0 nM insulin. |
| 509 | 15749807 | Thus, there is a selective reduction of total STAT3 protein levels by insulin, but only at high concentration of insulin. |
| 510 | 15749807 | Basal tyrosine phosphorylated (PY)-STAT3 was also significantly reduced by prolonged insulin treatment, and to a greater extent than total STAT3 protein levels. |
| 511 | 15749807 | The inhibitory effect of insulin on total STAT3 protein and basal PY-STAT3 levels was dependent on activation of the MEK-ERK pathway, rather than the PI3K pathway. |
| 512 | 15749807 | In contrast, the MEK-ERK pathway did not play a major role in insulin's inhibition of GH-induced PY-STAT3 and PY-STAT1. |
| 513 | 15749807 | The present studies indicate that prolonged hyperinsulinemia, such as that found in some obese patients or patients with Type 2 diabetes mellitus, may have profound effects on GH signaling via STAT3 and STAT1. |
| 514 | 15749807 | Prolonged insulin treatment inhibits GH signaling via STAT3 and STAT1. |
| 515 | 15749807 | Previous studies in our laboratory have shown that GH induction of signal transducers and activators of transcription (STAT)5B tyrosine phosphorylation is inhibited by prolonged insulin treatment, probably via downregulation of GHR. |
| 516 | 15749807 | Here, we find that in rat H4IIE hepatoma cells GH-induced tyrosine phosphorylation of two other STATs (STAT3 and STAT1) was also greatly reduced following prolonged insulin pretreatment compared with that induced by GH alone. |
| 517 | 15749807 | In the present work, total STAT5B and STAT1 protein levels were not altered by prolonged insulin treatment. |
| 518 | 15749807 | However, prolonged insulin treatment (16 h; 10 or 100 nM) resulted in a 30-40% reduction of total STAT3 protein, with little change at 0.1 and 1.0 nM insulin. |
| 519 | 15749807 | Thus, there is a selective reduction of total STAT3 protein levels by insulin, but only at high concentration of insulin. |
| 520 | 15749807 | Basal tyrosine phosphorylated (PY)-STAT3 was also significantly reduced by prolonged insulin treatment, and to a greater extent than total STAT3 protein levels. |
| 521 | 15749807 | The inhibitory effect of insulin on total STAT3 protein and basal PY-STAT3 levels was dependent on activation of the MEK-ERK pathway, rather than the PI3K pathway. |
| 522 | 15749807 | In contrast, the MEK-ERK pathway did not play a major role in insulin's inhibition of GH-induced PY-STAT3 and PY-STAT1. |
| 523 | 15749807 | The present studies indicate that prolonged hyperinsulinemia, such as that found in some obese patients or patients with Type 2 diabetes mellitus, may have profound effects on GH signaling via STAT3 and STAT1. |
| 524 | 15749807 | Prolonged insulin treatment inhibits GH signaling via STAT3 and STAT1. |
| 525 | 15749807 | Previous studies in our laboratory have shown that GH induction of signal transducers and activators of transcription (STAT)5B tyrosine phosphorylation is inhibited by prolonged insulin treatment, probably via downregulation of GHR. |
| 526 | 15749807 | Here, we find that in rat H4IIE hepatoma cells GH-induced tyrosine phosphorylation of two other STATs (STAT3 and STAT1) was also greatly reduced following prolonged insulin pretreatment compared with that induced by GH alone. |
| 527 | 15749807 | In the present work, total STAT5B and STAT1 protein levels were not altered by prolonged insulin treatment. |
| 528 | 15749807 | However, prolonged insulin treatment (16 h; 10 or 100 nM) resulted in a 30-40% reduction of total STAT3 protein, with little change at 0.1 and 1.0 nM insulin. |
| 529 | 15749807 | Thus, there is a selective reduction of total STAT3 protein levels by insulin, but only at high concentration of insulin. |
| 530 | 15749807 | Basal tyrosine phosphorylated (PY)-STAT3 was also significantly reduced by prolonged insulin treatment, and to a greater extent than total STAT3 protein levels. |
| 531 | 15749807 | The inhibitory effect of insulin on total STAT3 protein and basal PY-STAT3 levels was dependent on activation of the MEK-ERK pathway, rather than the PI3K pathway. |
| 532 | 15749807 | In contrast, the MEK-ERK pathway did not play a major role in insulin's inhibition of GH-induced PY-STAT3 and PY-STAT1. |
| 533 | 15749807 | The present studies indicate that prolonged hyperinsulinemia, such as that found in some obese patients or patients with Type 2 diabetes mellitus, may have profound effects on GH signaling via STAT3 and STAT1. |
| 534 | 15749807 | Prolonged insulin treatment inhibits GH signaling via STAT3 and STAT1. |
| 535 | 15749807 | Previous studies in our laboratory have shown that GH induction of signal transducers and activators of transcription (STAT)5B tyrosine phosphorylation is inhibited by prolonged insulin treatment, probably via downregulation of GHR. |
| 536 | 15749807 | Here, we find that in rat H4IIE hepatoma cells GH-induced tyrosine phosphorylation of two other STATs (STAT3 and STAT1) was also greatly reduced following prolonged insulin pretreatment compared with that induced by GH alone. |
| 537 | 15749807 | In the present work, total STAT5B and STAT1 protein levels were not altered by prolonged insulin treatment. |
| 538 | 15749807 | However, prolonged insulin treatment (16 h; 10 or 100 nM) resulted in a 30-40% reduction of total STAT3 protein, with little change at 0.1 and 1.0 nM insulin. |
| 539 | 15749807 | Thus, there is a selective reduction of total STAT3 protein levels by insulin, but only at high concentration of insulin. |
| 540 | 15749807 | Basal tyrosine phosphorylated (PY)-STAT3 was also significantly reduced by prolonged insulin treatment, and to a greater extent than total STAT3 protein levels. |
| 541 | 15749807 | The inhibitory effect of insulin on total STAT3 protein and basal PY-STAT3 levels was dependent on activation of the MEK-ERK pathway, rather than the PI3K pathway. |
| 542 | 15749807 | In contrast, the MEK-ERK pathway did not play a major role in insulin's inhibition of GH-induced PY-STAT3 and PY-STAT1. |
| 543 | 15749807 | The present studies indicate that prolonged hyperinsulinemia, such as that found in some obese patients or patients with Type 2 diabetes mellitus, may have profound effects on GH signaling via STAT3 and STAT1. |
| 544 | 15749807 | Prolonged insulin treatment inhibits GH signaling via STAT3 and STAT1. |
| 545 | 15749807 | Previous studies in our laboratory have shown that GH induction of signal transducers and activators of transcription (STAT)5B tyrosine phosphorylation is inhibited by prolonged insulin treatment, probably via downregulation of GHR. |
| 546 | 15749807 | Here, we find that in rat H4IIE hepatoma cells GH-induced tyrosine phosphorylation of two other STATs (STAT3 and STAT1) was also greatly reduced following prolonged insulin pretreatment compared with that induced by GH alone. |
| 547 | 15749807 | In the present work, total STAT5B and STAT1 protein levels were not altered by prolonged insulin treatment. |
| 548 | 15749807 | However, prolonged insulin treatment (16 h; 10 or 100 nM) resulted in a 30-40% reduction of total STAT3 protein, with little change at 0.1 and 1.0 nM insulin. |
| 549 | 15749807 | Thus, there is a selective reduction of total STAT3 protein levels by insulin, but only at high concentration of insulin. |
| 550 | 15749807 | Basal tyrosine phosphorylated (PY)-STAT3 was also significantly reduced by prolonged insulin treatment, and to a greater extent than total STAT3 protein levels. |
| 551 | 15749807 | The inhibitory effect of insulin on total STAT3 protein and basal PY-STAT3 levels was dependent on activation of the MEK-ERK pathway, rather than the PI3K pathway. |
| 552 | 15749807 | In contrast, the MEK-ERK pathway did not play a major role in insulin's inhibition of GH-induced PY-STAT3 and PY-STAT1. |
| 553 | 15749807 | The present studies indicate that prolonged hyperinsulinemia, such as that found in some obese patients or patients with Type 2 diabetes mellitus, may have profound effects on GH signaling via STAT3 and STAT1. |
| 554 | 15749807 | Prolonged insulin treatment inhibits GH signaling via STAT3 and STAT1. |
| 555 | 15749807 | Previous studies in our laboratory have shown that GH induction of signal transducers and activators of transcription (STAT)5B tyrosine phosphorylation is inhibited by prolonged insulin treatment, probably via downregulation of GHR. |
| 556 | 15749807 | Here, we find that in rat H4IIE hepatoma cells GH-induced tyrosine phosphorylation of two other STATs (STAT3 and STAT1) was also greatly reduced following prolonged insulin pretreatment compared with that induced by GH alone. |
| 557 | 15749807 | In the present work, total STAT5B and STAT1 protein levels were not altered by prolonged insulin treatment. |
| 558 | 15749807 | However, prolonged insulin treatment (16 h; 10 or 100 nM) resulted in a 30-40% reduction of total STAT3 protein, with little change at 0.1 and 1.0 nM insulin. |
| 559 | 15749807 | Thus, there is a selective reduction of total STAT3 protein levels by insulin, but only at high concentration of insulin. |
| 560 | 15749807 | Basal tyrosine phosphorylated (PY)-STAT3 was also significantly reduced by prolonged insulin treatment, and to a greater extent than total STAT3 protein levels. |
| 561 | 15749807 | The inhibitory effect of insulin on total STAT3 protein and basal PY-STAT3 levels was dependent on activation of the MEK-ERK pathway, rather than the PI3K pathway. |
| 562 | 15749807 | In contrast, the MEK-ERK pathway did not play a major role in insulin's inhibition of GH-induced PY-STAT3 and PY-STAT1. |
| 563 | 15749807 | The present studies indicate that prolonged hyperinsulinemia, such as that found in some obese patients or patients with Type 2 diabetes mellitus, may have profound effects on GH signaling via STAT3 and STAT1. |
| 564 | 15749807 | Prolonged insulin treatment inhibits GH signaling via STAT3 and STAT1. |
| 565 | 15749807 | Previous studies in our laboratory have shown that GH induction of signal transducers and activators of transcription (STAT)5B tyrosine phosphorylation is inhibited by prolonged insulin treatment, probably via downregulation of GHR. |
| 566 | 15749807 | Here, we find that in rat H4IIE hepatoma cells GH-induced tyrosine phosphorylation of two other STATs (STAT3 and STAT1) was also greatly reduced following prolonged insulin pretreatment compared with that induced by GH alone. |
| 567 | 15749807 | In the present work, total STAT5B and STAT1 protein levels were not altered by prolonged insulin treatment. |
| 568 | 15749807 | However, prolonged insulin treatment (16 h; 10 or 100 nM) resulted in a 30-40% reduction of total STAT3 protein, with little change at 0.1 and 1.0 nM insulin. |
| 569 | 15749807 | Thus, there is a selective reduction of total STAT3 protein levels by insulin, but only at high concentration of insulin. |
| 570 | 15749807 | Basal tyrosine phosphorylated (PY)-STAT3 was also significantly reduced by prolonged insulin treatment, and to a greater extent than total STAT3 protein levels. |
| 571 | 15749807 | The inhibitory effect of insulin on total STAT3 protein and basal PY-STAT3 levels was dependent on activation of the MEK-ERK pathway, rather than the PI3K pathway. |
| 572 | 15749807 | In contrast, the MEK-ERK pathway did not play a major role in insulin's inhibition of GH-induced PY-STAT3 and PY-STAT1. |
| 573 | 15749807 | The present studies indicate that prolonged hyperinsulinemia, such as that found in some obese patients or patients with Type 2 diabetes mellitus, may have profound effects on GH signaling via STAT3 and STAT1. |
| 574 | 15913829 | Here we show that overexpression of suppressors of cytokine signaling (SOCS)-1 and SOCS-3 in liver causes insulin resistance and an increase in the key regulator of fatty acid synthesis in liver, sterol regulatory element-binding protein (SREBP)-1c. |
| 575 | 15913829 | Conversely, inhibition of SOCS-1 and -3 in obese diabetic mice improves insulin sensitivity, normalizes the increased expression of SREBP-1c, and dramatically ameliorates hepatic steatosis and hypertriglyceridemia. |
| 576 | 15913829 | In obese animals, increased SOCS proteins enhance SREBP-1c expression by antagonizing STAT3-mediated inhibition of SREBP-1c promoter activity. |
| 577 | 15913829 | Thus, SOCS proteins play an important role in pathogenesis of the metabolic syndrome by concordantly modulating insulin signaling and cytokine signaling. |
| 578 | 16026757 | The transcription factor Stat3 is activated by multiple cytokines, including leptin and those signaling through the gp130 receptor. |
| 579 | 16026757 | In two independent studies, mice in which the Stat3 gene was inactivated using a RIP-Cre transgene led to glucose intolerance, defects in early-phase insulin secretion, and mild obesity [S. |
| 580 | 16026757 | Hori, Insulin secretory defects and impaired islet architecture in pancreatic beta-cell-specific STAT3 knockout mice, Biochem. |
| 581 | 16026757 | However, since the RIP-Cre transgene is also expressed in the hypothalamus, and thereby Stat3 was deleted from neurons expressing the leptin receptor, it was not clear as to which of the metabolic defects were due to the loss of Stat3 from beta-cells or the hypothalamus. |
| 582 | 16026757 | We have addressed this issue through the inactivation of Stat3 from pancreatic beta-cells using a Pdx1-Cre transgene. |
| 583 | 16026757 | Complete loss of Stat3 was observed in islets from mice, which carry two floxed Stat3 alleles and the Pdx1-Cre transgene. |
| 584 | 16026757 | The transcription factor Stat3 is activated by multiple cytokines, including leptin and those signaling through the gp130 receptor. |
| 585 | 16026757 | In two independent studies, mice in which the Stat3 gene was inactivated using a RIP-Cre transgene led to glucose intolerance, defects in early-phase insulin secretion, and mild obesity [S. |
| 586 | 16026757 | Hori, Insulin secretory defects and impaired islet architecture in pancreatic beta-cell-specific STAT3 knockout mice, Biochem. |
| 587 | 16026757 | However, since the RIP-Cre transgene is also expressed in the hypothalamus, and thereby Stat3 was deleted from neurons expressing the leptin receptor, it was not clear as to which of the metabolic defects were due to the loss of Stat3 from beta-cells or the hypothalamus. |
| 588 | 16026757 | We have addressed this issue through the inactivation of Stat3 from pancreatic beta-cells using a Pdx1-Cre transgene. |
| 589 | 16026757 | Complete loss of Stat3 was observed in islets from mice, which carry two floxed Stat3 alleles and the Pdx1-Cre transgene. |
| 590 | 16026757 | The transcription factor Stat3 is activated by multiple cytokines, including leptin and those signaling through the gp130 receptor. |
| 591 | 16026757 | In two independent studies, mice in which the Stat3 gene was inactivated using a RIP-Cre transgene led to glucose intolerance, defects in early-phase insulin secretion, and mild obesity [S. |
| 592 | 16026757 | Hori, Insulin secretory defects and impaired islet architecture in pancreatic beta-cell-specific STAT3 knockout mice, Biochem. |
| 593 | 16026757 | However, since the RIP-Cre transgene is also expressed in the hypothalamus, and thereby Stat3 was deleted from neurons expressing the leptin receptor, it was not clear as to which of the metabolic defects were due to the loss of Stat3 from beta-cells or the hypothalamus. |
| 594 | 16026757 | We have addressed this issue through the inactivation of Stat3 from pancreatic beta-cells using a Pdx1-Cre transgene. |
| 595 | 16026757 | Complete loss of Stat3 was observed in islets from mice, which carry two floxed Stat3 alleles and the Pdx1-Cre transgene. |
| 596 | 16026757 | The transcription factor Stat3 is activated by multiple cytokines, including leptin and those signaling through the gp130 receptor. |
| 597 | 16026757 | In two independent studies, mice in which the Stat3 gene was inactivated using a RIP-Cre transgene led to glucose intolerance, defects in early-phase insulin secretion, and mild obesity [S. |
| 598 | 16026757 | Hori, Insulin secretory defects and impaired islet architecture in pancreatic beta-cell-specific STAT3 knockout mice, Biochem. |
| 599 | 16026757 | However, since the RIP-Cre transgene is also expressed in the hypothalamus, and thereby Stat3 was deleted from neurons expressing the leptin receptor, it was not clear as to which of the metabolic defects were due to the loss of Stat3 from beta-cells or the hypothalamus. |
| 600 | 16026757 | We have addressed this issue through the inactivation of Stat3 from pancreatic beta-cells using a Pdx1-Cre transgene. |
| 601 | 16026757 | Complete loss of Stat3 was observed in islets from mice, which carry two floxed Stat3 alleles and the Pdx1-Cre transgene. |
| 602 | 16026757 | The transcription factor Stat3 is activated by multiple cytokines, including leptin and those signaling through the gp130 receptor. |
| 603 | 16026757 | In two independent studies, mice in which the Stat3 gene was inactivated using a RIP-Cre transgene led to glucose intolerance, defects in early-phase insulin secretion, and mild obesity [S. |
| 604 | 16026757 | Hori, Insulin secretory defects and impaired islet architecture in pancreatic beta-cell-specific STAT3 knockout mice, Biochem. |
| 605 | 16026757 | However, since the RIP-Cre transgene is also expressed in the hypothalamus, and thereby Stat3 was deleted from neurons expressing the leptin receptor, it was not clear as to which of the metabolic defects were due to the loss of Stat3 from beta-cells or the hypothalamus. |
| 606 | 16026757 | We have addressed this issue through the inactivation of Stat3 from pancreatic beta-cells using a Pdx1-Cre transgene. |
| 607 | 16026757 | Complete loss of Stat3 was observed in islets from mice, which carry two floxed Stat3 alleles and the Pdx1-Cre transgene. |
| 608 | 16026757 | The transcription factor Stat3 is activated by multiple cytokines, including leptin and those signaling through the gp130 receptor. |
| 609 | 16026757 | In two independent studies, mice in which the Stat3 gene was inactivated using a RIP-Cre transgene led to glucose intolerance, defects in early-phase insulin secretion, and mild obesity [S. |
| 610 | 16026757 | Hori, Insulin secretory defects and impaired islet architecture in pancreatic beta-cell-specific STAT3 knockout mice, Biochem. |
| 611 | 16026757 | However, since the RIP-Cre transgene is also expressed in the hypothalamus, and thereby Stat3 was deleted from neurons expressing the leptin receptor, it was not clear as to which of the metabolic defects were due to the loss of Stat3 from beta-cells or the hypothalamus. |
| 612 | 16026757 | We have addressed this issue through the inactivation of Stat3 from pancreatic beta-cells using a Pdx1-Cre transgene. |
| 613 | 16026757 | Complete loss of Stat3 was observed in islets from mice, which carry two floxed Stat3 alleles and the Pdx1-Cre transgene. |
| 614 | 16054060 | Roles for leptin receptor/STAT3-dependent and -independent signals in the regulation of glucose homeostasis. |
| 615 | 16054060 | While adiposity influences insulin sensitivity, leptin also regulates glucose homeostasis independently of energy balance. |
| 616 | 16054060 | Insulin resistance and glucose intolerance are improved in s/s compared to db/db animals, however, suggesting that LRb/STAT3-independent signals may contribute to the regulation of glucose homeostasis by leptin. |
| 617 | 16054060 | Thus, in addition to LRb/STAT3-mediated adiposity signals, non-LRb/STAT3 leptin signals mediate an important adiposity-independent role in promoting glycemic control. |
| 618 | 16054060 | Roles for leptin receptor/STAT3-dependent and -independent signals in the regulation of glucose homeostasis. |
| 619 | 16054060 | While adiposity influences insulin sensitivity, leptin also regulates glucose homeostasis independently of energy balance. |
| 620 | 16054060 | Insulin resistance and glucose intolerance are improved in s/s compared to db/db animals, however, suggesting that LRb/STAT3-independent signals may contribute to the regulation of glucose homeostasis by leptin. |
| 621 | 16054060 | Thus, in addition to LRb/STAT3-mediated adiposity signals, non-LRb/STAT3 leptin signals mediate an important adiposity-independent role in promoting glycemic control. |
| 622 | 16054060 | Roles for leptin receptor/STAT3-dependent and -independent signals in the regulation of glucose homeostasis. |
| 623 | 16054060 | While adiposity influences insulin sensitivity, leptin also regulates glucose homeostasis independently of energy balance. |
| 624 | 16054060 | Insulin resistance and glucose intolerance are improved in s/s compared to db/db animals, however, suggesting that LRb/STAT3-independent signals may contribute to the regulation of glucose homeostasis by leptin. |
| 625 | 16054060 | Thus, in addition to LRb/STAT3-mediated adiposity signals, non-LRb/STAT3 leptin signals mediate an important adiposity-independent role in promoting glycemic control. |
| 626 | 16123338 | Cardiac-specific overexpression of peroxisome proliferator-activated receptor-alpha causes insulin resistance in heart and liver. |
| 627 | 16123338 | Mice with heart-specific overexpression of peroxisome proliferator-activated receptor (PPAR)alpha showed a metabolic and cardiomyopathic phenotype similar to the diabetic heart, and we determined tissue-specific glucose metabolism and insulin action in vivo during hyperinsulinemic-euglycemic clamps in awake myosin heavy chain (MHC)-PPARalpha mice (12-14 weeks of age). |
| 628 | 16123338 | Basal and insulin-stimulated glucose uptake in heart was significantly reduced in the MHC-PPARalpha mice, and cardiac insulin resistance was mostly attributed to defects in insulin-stimulated activities of insulin receptor substrate (IRS)-1-associated phosphatidylinositol (PI) 3-kinase, Akt, and tyrosine phosphorylation of signal transducer and activator of transcription 3 (STAT3). |
| 629 | 16123338 | Interestingly, MHC-PPARalpha mice developed hepatic insulin resistance associated with defects in insulin-mediated IRS-2-associated PI 3-kinase activity, increased hepatic triglyceride, and circulating interleukin-6 levels. |
| 630 | 16123338 | Overall, these findings indicate that increased activity of PPARalpha, as occurs in the diabetic heart, leads to cardiac insulin resistance associated with defects in insulin signaling and STAT3 activity, subsequently leading to reduced cardiac function. |
| 631 | 16123338 | Cardiac-specific overexpression of peroxisome proliferator-activated receptor-alpha causes insulin resistance in heart and liver. |
| 632 | 16123338 | Mice with heart-specific overexpression of peroxisome proliferator-activated receptor (PPAR)alpha showed a metabolic and cardiomyopathic phenotype similar to the diabetic heart, and we determined tissue-specific glucose metabolism and insulin action in vivo during hyperinsulinemic-euglycemic clamps in awake myosin heavy chain (MHC)-PPARalpha mice (12-14 weeks of age). |
| 633 | 16123338 | Basal and insulin-stimulated glucose uptake in heart was significantly reduced in the MHC-PPARalpha mice, and cardiac insulin resistance was mostly attributed to defects in insulin-stimulated activities of insulin receptor substrate (IRS)-1-associated phosphatidylinositol (PI) 3-kinase, Akt, and tyrosine phosphorylation of signal transducer and activator of transcription 3 (STAT3). |
| 634 | 16123338 | Interestingly, MHC-PPARalpha mice developed hepatic insulin resistance associated with defects in insulin-mediated IRS-2-associated PI 3-kinase activity, increased hepatic triglyceride, and circulating interleukin-6 levels. |
| 635 | 16123338 | Overall, these findings indicate that increased activity of PPARalpha, as occurs in the diabetic heart, leads to cardiac insulin resistance associated with defects in insulin signaling and STAT3 activity, subsequently leading to reduced cardiac function. |
| 636 | 16177100 | Nonobese diabetic mouse congenic analysis reveals chromosome 11 locus contributing to diabetes susceptibility, macrophage STAT5 dysfunction, and granulocyte-macrophage colony-stimulating factor overproduction. |
| 637 | 16177100 | Unstimulated monocytes of at-risk/type 1 diabetic humans and macrophages of the NOD mouse have markedly elevated autocrine GM-CSF production and persistent STAT5 phosphorylation. |
| 638 | 16177100 | We analyzed the relationship between GM-CSF production and persistent STAT5 phosphorylation in NOD macrophages using reciprocal congenic mouse strains containing either diabetes-susceptible NOD (B6.NODC11), or diabetes-resistant C57L (NOD.LC11) loci on chromosome 11. |
| 639 | 16177100 | These intervals contain the gene for GM-CSF (Csf2; 53.8 Mb) and those for STAT3, STAT5A, and STAT5B (Stat3, Stat5a, and Stat5b; 100.4-100.6 Mb). |
| 640 | 16177100 | High GM-CSF production and persistent STAT5 phosphorylation in unactivated NOD macrophages can be linked to a region (44.9-55.7 Mb) containing the Csf2 gene, but not the Stat3/5a/5b genes. |
| 641 | 16177100 | Nonobese diabetic mouse congenic analysis reveals chromosome 11 locus contributing to diabetes susceptibility, macrophage STAT5 dysfunction, and granulocyte-macrophage colony-stimulating factor overproduction. |
| 642 | 16177100 | Unstimulated monocytes of at-risk/type 1 diabetic humans and macrophages of the NOD mouse have markedly elevated autocrine GM-CSF production and persistent STAT5 phosphorylation. |
| 643 | 16177100 | We analyzed the relationship between GM-CSF production and persistent STAT5 phosphorylation in NOD macrophages using reciprocal congenic mouse strains containing either diabetes-susceptible NOD (B6.NODC11), or diabetes-resistant C57L (NOD.LC11) loci on chromosome 11. |
| 644 | 16177100 | These intervals contain the gene for GM-CSF (Csf2; 53.8 Mb) and those for STAT3, STAT5A, and STAT5B (Stat3, Stat5a, and Stat5b; 100.4-100.6 Mb). |
| 645 | 16177100 | High GM-CSF production and persistent STAT5 phosphorylation in unactivated NOD macrophages can be linked to a region (44.9-55.7 Mb) containing the Csf2 gene, but not the Stat3/5a/5b genes. |
| 646 | 16226915 | Role of suppressors of cytokine signaling SOCS-1 and SOCS-3 in hepatic steatosis and the metabolic syndrome. |
| 647 | 16226915 | In this study, we show that expression of suppressor of cytokine signaling SOCS-1 and SOCS-3 is increased in livers of obese insulin-resistant animals, and that adenoviral-mediated overexpression of SOCS-1 or SOCS-3 in liver causes insulin resistance through down-regulation of tyrosine phosphorylation of insulin receptor substrate (IRS) proteins. |
| 648 | 16226915 | Moreover, the increased SOCS-1 and SOCS-3 also cause a prominent up-regulation of the key regulator of fatty acid synthesis in liver, sterol regulatory element binding protein (SREBP)-1. |
| 649 | 16226915 | Conversely, inhibition of SOCS-1 and SOCS-3 in livers of obese diabetic db/db mice by antisense treatment modestly improves insulin sensitivity, but completely normalizes the increased expression of SREBP-1. |
| 650 | 16226915 | Promoter activity analysis reveals that expression of SOCS-1 or SOCS-3 with SOCS-3 being more potent enhances SREBP-1c expression, while it is inhibited by expression of STAT3. |
| 651 | 16226915 | This STAT3-mediated inhibition of SREBP-1c expression is antagonized by co-expression of SOCS proteins. |
| 652 | 16226915 | Moreover, db/db mice display decreased STAT3 phosphorylation in liver that is normalized by antisense treatment of SOCS proteins. |
| 653 | 16226915 | These data suggest that obese subjects in the persistent inflammatory states, such as elevated circulating tumor necrosis factor-alpha, may have down-regulated STAT3-mediated signaling by increased SOCS proteins, leading to up-regulation of SREBP-1c expression and increased fatty acid synthesis in liver. |
| 654 | 16226915 | Thus, SOCS proteins play an important role in pathogenesis of the metabolic syndrome by concordantly modulating cytokine signaling and insulin signaling. |
| 655 | 16226915 | Role of suppressors of cytokine signaling SOCS-1 and SOCS-3 in hepatic steatosis and the metabolic syndrome. |
| 656 | 16226915 | In this study, we show that expression of suppressor of cytokine signaling SOCS-1 and SOCS-3 is increased in livers of obese insulin-resistant animals, and that adenoviral-mediated overexpression of SOCS-1 or SOCS-3 in liver causes insulin resistance through down-regulation of tyrosine phosphorylation of insulin receptor substrate (IRS) proteins. |
| 657 | 16226915 | Moreover, the increased SOCS-1 and SOCS-3 also cause a prominent up-regulation of the key regulator of fatty acid synthesis in liver, sterol regulatory element binding protein (SREBP)-1. |
| 658 | 16226915 | Conversely, inhibition of SOCS-1 and SOCS-3 in livers of obese diabetic db/db mice by antisense treatment modestly improves insulin sensitivity, but completely normalizes the increased expression of SREBP-1. |
| 659 | 16226915 | Promoter activity analysis reveals that expression of SOCS-1 or SOCS-3 with SOCS-3 being more potent enhances SREBP-1c expression, while it is inhibited by expression of STAT3. |
| 660 | 16226915 | This STAT3-mediated inhibition of SREBP-1c expression is antagonized by co-expression of SOCS proteins. |
| 661 | 16226915 | Moreover, db/db mice display decreased STAT3 phosphorylation in liver that is normalized by antisense treatment of SOCS proteins. |
| 662 | 16226915 | These data suggest that obese subjects in the persistent inflammatory states, such as elevated circulating tumor necrosis factor-alpha, may have down-regulated STAT3-mediated signaling by increased SOCS proteins, leading to up-regulation of SREBP-1c expression and increased fatty acid synthesis in liver. |
| 663 | 16226915 | Thus, SOCS proteins play an important role in pathogenesis of the metabolic syndrome by concordantly modulating cytokine signaling and insulin signaling. |
| 664 | 16226915 | Role of suppressors of cytokine signaling SOCS-1 and SOCS-3 in hepatic steatosis and the metabolic syndrome. |
| 665 | 16226915 | In this study, we show that expression of suppressor of cytokine signaling SOCS-1 and SOCS-3 is increased in livers of obese insulin-resistant animals, and that adenoviral-mediated overexpression of SOCS-1 or SOCS-3 in liver causes insulin resistance through down-regulation of tyrosine phosphorylation of insulin receptor substrate (IRS) proteins. |
| 666 | 16226915 | Moreover, the increased SOCS-1 and SOCS-3 also cause a prominent up-regulation of the key regulator of fatty acid synthesis in liver, sterol regulatory element binding protein (SREBP)-1. |
| 667 | 16226915 | Conversely, inhibition of SOCS-1 and SOCS-3 in livers of obese diabetic db/db mice by antisense treatment modestly improves insulin sensitivity, but completely normalizes the increased expression of SREBP-1. |
| 668 | 16226915 | Promoter activity analysis reveals that expression of SOCS-1 or SOCS-3 with SOCS-3 being more potent enhances SREBP-1c expression, while it is inhibited by expression of STAT3. |
| 669 | 16226915 | This STAT3-mediated inhibition of SREBP-1c expression is antagonized by co-expression of SOCS proteins. |
| 670 | 16226915 | Moreover, db/db mice display decreased STAT3 phosphorylation in liver that is normalized by antisense treatment of SOCS proteins. |
| 671 | 16226915 | These data suggest that obese subjects in the persistent inflammatory states, such as elevated circulating tumor necrosis factor-alpha, may have down-regulated STAT3-mediated signaling by increased SOCS proteins, leading to up-regulation of SREBP-1c expression and increased fatty acid synthesis in liver. |
| 672 | 16226915 | Thus, SOCS proteins play an important role in pathogenesis of the metabolic syndrome by concordantly modulating cytokine signaling and insulin signaling. |
| 673 | 16226915 | Role of suppressors of cytokine signaling SOCS-1 and SOCS-3 in hepatic steatosis and the metabolic syndrome. |
| 674 | 16226915 | In this study, we show that expression of suppressor of cytokine signaling SOCS-1 and SOCS-3 is increased in livers of obese insulin-resistant animals, and that adenoviral-mediated overexpression of SOCS-1 or SOCS-3 in liver causes insulin resistance through down-regulation of tyrosine phosphorylation of insulin receptor substrate (IRS) proteins. |
| 675 | 16226915 | Moreover, the increased SOCS-1 and SOCS-3 also cause a prominent up-regulation of the key regulator of fatty acid synthesis in liver, sterol regulatory element binding protein (SREBP)-1. |
| 676 | 16226915 | Conversely, inhibition of SOCS-1 and SOCS-3 in livers of obese diabetic db/db mice by antisense treatment modestly improves insulin sensitivity, but completely normalizes the increased expression of SREBP-1. |
| 677 | 16226915 | Promoter activity analysis reveals that expression of SOCS-1 or SOCS-3 with SOCS-3 being more potent enhances SREBP-1c expression, while it is inhibited by expression of STAT3. |
| 678 | 16226915 | This STAT3-mediated inhibition of SREBP-1c expression is antagonized by co-expression of SOCS proteins. |
| 679 | 16226915 | Moreover, db/db mice display decreased STAT3 phosphorylation in liver that is normalized by antisense treatment of SOCS proteins. |
| 680 | 16226915 | These data suggest that obese subjects in the persistent inflammatory states, such as elevated circulating tumor necrosis factor-alpha, may have down-regulated STAT3-mediated signaling by increased SOCS proteins, leading to up-regulation of SREBP-1c expression and increased fatty acid synthesis in liver. |
| 681 | 16226915 | Thus, SOCS proteins play an important role in pathogenesis of the metabolic syndrome by concordantly modulating cytokine signaling and insulin signaling. |
| 682 | 16249443 | Central leptin acutely reverses diet-induced hepatic insulin resistance. |
| 683 | 16249443 | Voluntary overfeeding rapidly induces resistance to the effects of systemic insulin and leptin on liver glucose metabolism. |
| 684 | 16249443 | To examine whether central administration of recombinant leptin can restore leptin and insulin action on liver glucose fluxes, we infused leptin in the third cerebral ventricle of conscious overfed rats during pancreatic-insulin clamp studies. |
| 685 | 16249443 | The effect of leptin on the phosphorylation of the signal transducer and activator of transcription-3 in the arcuate nuclei of the hypothalamus was similar in animals fed a regular diet or a high-fat diet for 3 days. |
| 686 | 16249443 | The inhibition of glycogenolysis was sufficient to normalize glucose production and was accompanied by leptin-induced decreases in the hepatic expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase. |
| 687 | 16249443 | Thus central administration of leptin rescues the hepatic insulin resistance induced by short-term hyperphagia. |
| 688 | 16289036 | In vitro experiments demonstrated that SOCS3 can inhibit PRL induction of milk protein gene expression and STAT5 activation. |
| 689 | 16289036 | Our results suggest that, in vivo, PRL stimulates SOCS3 expression in stromal adipocytes, independently of STAT5a stimulation. |
| 690 | 16289036 | In mammary epithelial cells, SOCS3 expression appears to be related to STAT3 activation. |
| 691 | 16297319 | [Effect of losartan on expression of Janus kinase 2 and signal transducer and activator of transcription 3 in glomeruli of diabetic rats]. |
| 692 | 16306356 | Inhibition of preproinsulin gene expression by leptin induction of suppressor of cytokine signaling 3 in pancreatic beta-cells. |
| 693 | 16306356 | Leptin inhibits insulin secretion and preproinsulin gene expression in pancreatic beta-cells, but signal transduction pathways and molecular mechanisms underlying this effect are poorly characterized. |
| 694 | 16306356 | Leptin stimulation led to janus kinase (JAK)2-dependent phosphorylation and nuclear translocation of the transcription factors signal transducer and activator of transcription (STAT)3 and STAT5b in INS-1 beta-cells. |
| 695 | 16306356 | Leptin also induced mRNA expression of the JAK-STAT inhibitor suppressor of cytokine signaling (SOCS)3 in INS-1 beta-cells and human pancreatic islets in vitro and in pancreatic islets of ob/ob mice in vivo. |
| 696 | 16306356 | Transcriptional activation of the rat SOCS3 promoter by leptin was observed with concomitant leptin-induced STAT3 and STAT5b DNA binding to specific promoter regions. |
| 697 | 16306356 | Unexpectedly, SOCS3 inhibited both basal and STAT3/5b-dependent rat preproinsulin 1 gene promoter activity in INS-1 cells. |
| 698 | 16306356 | These results suggest that SOCS3 represents a transcriptional inhibitor of preproinsulin gene expression, which is induced by leptin through JAK-STAT3/5b signaling in pancreatic beta-cells. |
| 699 | 16306356 | In conclusion, although SOCS3 is believed to be a negative feedback regulator of JAK-STAT signaling, our findings suggest involvement of SOCS3 in a direct gene regulatory pathway downstream of leptin-activated JAK-STAT signaling in pancreatic beta-cells. |
| 700 | 16306356 | Inhibition of preproinsulin gene expression by leptin induction of suppressor of cytokine signaling 3 in pancreatic beta-cells. |
| 701 | 16306356 | Leptin inhibits insulin secretion and preproinsulin gene expression in pancreatic beta-cells, but signal transduction pathways and molecular mechanisms underlying this effect are poorly characterized. |
| 702 | 16306356 | Leptin stimulation led to janus kinase (JAK)2-dependent phosphorylation and nuclear translocation of the transcription factors signal transducer and activator of transcription (STAT)3 and STAT5b in INS-1 beta-cells. |
| 703 | 16306356 | Leptin also induced mRNA expression of the JAK-STAT inhibitor suppressor of cytokine signaling (SOCS)3 in INS-1 beta-cells and human pancreatic islets in vitro and in pancreatic islets of ob/ob mice in vivo. |
| 704 | 16306356 | Transcriptional activation of the rat SOCS3 promoter by leptin was observed with concomitant leptin-induced STAT3 and STAT5b DNA binding to specific promoter regions. |
| 705 | 16306356 | Unexpectedly, SOCS3 inhibited both basal and STAT3/5b-dependent rat preproinsulin 1 gene promoter activity in INS-1 cells. |
| 706 | 16306356 | These results suggest that SOCS3 represents a transcriptional inhibitor of preproinsulin gene expression, which is induced by leptin through JAK-STAT3/5b signaling in pancreatic beta-cells. |
| 707 | 16306356 | In conclusion, although SOCS3 is believed to be a negative feedback regulator of JAK-STAT signaling, our findings suggest involvement of SOCS3 in a direct gene regulatory pathway downstream of leptin-activated JAK-STAT signaling in pancreatic beta-cells. |
| 708 | 16306356 | Inhibition of preproinsulin gene expression by leptin induction of suppressor of cytokine signaling 3 in pancreatic beta-cells. |
| 709 | 16306356 | Leptin inhibits insulin secretion and preproinsulin gene expression in pancreatic beta-cells, but signal transduction pathways and molecular mechanisms underlying this effect are poorly characterized. |
| 710 | 16306356 | Leptin stimulation led to janus kinase (JAK)2-dependent phosphorylation and nuclear translocation of the transcription factors signal transducer and activator of transcription (STAT)3 and STAT5b in INS-1 beta-cells. |
| 711 | 16306356 | Leptin also induced mRNA expression of the JAK-STAT inhibitor suppressor of cytokine signaling (SOCS)3 in INS-1 beta-cells and human pancreatic islets in vitro and in pancreatic islets of ob/ob mice in vivo. |
| 712 | 16306356 | Transcriptional activation of the rat SOCS3 promoter by leptin was observed with concomitant leptin-induced STAT3 and STAT5b DNA binding to specific promoter regions. |
| 713 | 16306356 | Unexpectedly, SOCS3 inhibited both basal and STAT3/5b-dependent rat preproinsulin 1 gene promoter activity in INS-1 cells. |
| 714 | 16306356 | These results suggest that SOCS3 represents a transcriptional inhibitor of preproinsulin gene expression, which is induced by leptin through JAK-STAT3/5b signaling in pancreatic beta-cells. |
| 715 | 16306356 | In conclusion, although SOCS3 is believed to be a negative feedback regulator of JAK-STAT signaling, our findings suggest involvement of SOCS3 in a direct gene regulatory pathway downstream of leptin-activated JAK-STAT signaling in pancreatic beta-cells. |
| 716 | 16306356 | Inhibition of preproinsulin gene expression by leptin induction of suppressor of cytokine signaling 3 in pancreatic beta-cells. |
| 717 | 16306356 | Leptin inhibits insulin secretion and preproinsulin gene expression in pancreatic beta-cells, but signal transduction pathways and molecular mechanisms underlying this effect are poorly characterized. |
| 718 | 16306356 | Leptin stimulation led to janus kinase (JAK)2-dependent phosphorylation and nuclear translocation of the transcription factors signal transducer and activator of transcription (STAT)3 and STAT5b in INS-1 beta-cells. |
| 719 | 16306356 | Leptin also induced mRNA expression of the JAK-STAT inhibitor suppressor of cytokine signaling (SOCS)3 in INS-1 beta-cells and human pancreatic islets in vitro and in pancreatic islets of ob/ob mice in vivo. |
| 720 | 16306356 | Transcriptional activation of the rat SOCS3 promoter by leptin was observed with concomitant leptin-induced STAT3 and STAT5b DNA binding to specific promoter regions. |
| 721 | 16306356 | Unexpectedly, SOCS3 inhibited both basal and STAT3/5b-dependent rat preproinsulin 1 gene promoter activity in INS-1 cells. |
| 722 | 16306356 | These results suggest that SOCS3 represents a transcriptional inhibitor of preproinsulin gene expression, which is induced by leptin through JAK-STAT3/5b signaling in pancreatic beta-cells. |
| 723 | 16306356 | In conclusion, although SOCS3 is believed to be a negative feedback regulator of JAK-STAT signaling, our findings suggest involvement of SOCS3 in a direct gene regulatory pathway downstream of leptin-activated JAK-STAT signaling in pancreatic beta-cells. |
| 724 | 16326804 | In 6 days of a HFD, mRNA of the postreceptor leptin inhibitor, suppressor of cytokine signaling-3, increased 22-fold in WAT, while leptin receptor (Lepr-b) mRNA gradually disappeared, implying leptinergic blockade at both postreceptor and receptor levels. |
| 725 | 16326804 | Activated STAT-3 and AMP-activated protein kinase (AMPK), and the mRNA of lipooxidative enzymes, peroxisome proliferator-activated receptor-gamma-coactivator-1alpha, and uncoupling protein-1 and -2 were increased in WAT. |
| 726 | 16449352 | Effect of simvastatin on high glucose- and angiotensin II-induced activation of the JAK/STAT pathway in mesangial cells. |
| 727 | 16449352 | We found that pretreatment with simvastatin significantly inhibited HG- and ANG II-induced collagen IV production, JAK2 activation, and phosphorylation of STAT1 and STAT3 in GMC. |
| 728 | 16449352 | We also found that the activation of JAK2 by HG and ANG II was dependent on the Rho family of GTPases. |
| 729 | 16449352 | Consistent with these in vitro results, both albumin protein excretion and phosphorylation of JAK2, STAT1, and STAT3 were attenuated in renal glomeruli by administration of simvastatin in a streptozotocin-induced rat model of HG diabetes. |
| 730 | 16449352 | This study demonstrates that simvastatin blocks ANG II-induced activation of the JAK/STAT pathway in the diabetic environment, in vitro and in vivo, and, thereby, provides new insights into the molecular mechanisms underlying early diabetic nephropathy. |
| 731 | 16449352 | Effect of simvastatin on high glucose- and angiotensin II-induced activation of the JAK/STAT pathway in mesangial cells. |
| 732 | 16449352 | We found that pretreatment with simvastatin significantly inhibited HG- and ANG II-induced collagen IV production, JAK2 activation, and phosphorylation of STAT1 and STAT3 in GMC. |
| 733 | 16449352 | We also found that the activation of JAK2 by HG and ANG II was dependent on the Rho family of GTPases. |
| 734 | 16449352 | Consistent with these in vitro results, both albumin protein excretion and phosphorylation of JAK2, STAT1, and STAT3 were attenuated in renal glomeruli by administration of simvastatin in a streptozotocin-induced rat model of HG diabetes. |
| 735 | 16449352 | This study demonstrates that simvastatin blocks ANG II-induced activation of the JAK/STAT pathway in the diabetic environment, in vitro and in vivo, and, thereby, provides new insights into the molecular mechanisms underlying early diabetic nephropathy. |
| 736 | 16505217 | Divergent regulation of proopiomelanocortin neurons by leptin in the nucleus of the solitary tract and in the arcuate hypothalamic nucleus. |
| 737 | 16505217 | Proopiomelanocortin (POMC) neurons in the arcuate nucleus (ARC) of the hypothalamus are activated by leptin and mediate part of leptin's central actions to influence energy balance. |
| 738 | 16505217 | However, little is known about potential leptin signaling in POMC neurons located in the nucleus of the solitary tract (NTS), the only other known population of POMC neurons. |
| 739 | 16505217 | The contribution of NTS POMC neurons versus ARC POMC neurons in leptin action is thus undetermined. |
| 740 | 16505217 | We show here that in contrast to POMC neurons in the ARC, leptin does not stimulate phosphorylation of signal-transducer and activator of transcription 3 in NTS POMC neurons of POMC-EGFP reporter mice. |
| 741 | 16505217 | In addition, leptin does not induce c-Fos expression in NTS POMC neurons unlike ARC POMC neurons. |
| 742 | 16505217 | Fasting induces a fall in POMC mRNA in both the ARC and the NTS, but different from the ARC, the reduction in NTS POMC mRNA is not reversed by leptin. |
| 743 | 16505217 | We conclude that POMC neurons in the NTS do not respond to leptin unlike ARC POMC neurons. |
| 744 | 16505217 | POMC neurons in the hypothalamus may therefore mediate all of leptin's signaling via POMC-derived peptides in the central nervous system. |
| 745 | 16505235 | Moreover, serum concentrations of leptin and insulin were decreased dramatically by leptin in metformin-treated standard chow and high-fat-fed obese rats. |
| 746 | 16505235 | The hypothalamic phosphorylated AMP-activated protein kinase level was decreased by lower leptin dose in metformin-treated rats than in untreated rats. |
| 747 | 16505235 | In an acute study, metformin treatment also increased the anorexic effect of leptin (5 microg), and this was accompanied by an increased level of phosphorylated signal transducer and activator of transcription 3 in the hypothalamus. |
| 748 | 16514419 | Inhibition of EGF and LIF signalling by pharmacological antagonists of the JAK2/STAT3 pathway, or knockdown of Ngn3 by RNA interference prevented the generation of new insulin-positive cells. |
| 749 | 16551628 | An inhibitor of Src kinase, PP2, significantly blocked S100B-induced activation of Src kinase, mitogen-activated protein kinases, transcription factors NF-kappaB and STAT3, superoxide production, tyrosine phosphorylation of Cav-1, VSMC migration, and expression of the pro-inflammatory genes monocyte chemotactic protein-1 and interleukin-6. |
| 750 | 16581004 | Role of hepatic STAT3 in brain-insulin action on hepatic glucose production. |
| 751 | 16581004 | Here, we show that an increase in the plasma insulin concentration, achieved either by glucose administration or by intravenous insulin infusion, stimulates tyrosine phosphorylation of STAT3 in the liver. |
| 752 | 16581004 | This effect of insulin was mediated by the hormone's effects in the brain, and the increase in hepatic IL-6 induced by the brain-insulin action is essential for the activation of STAT3. |
| 753 | 16581004 | The inhibition of hepatic glucose production and of expression of gluconeogenic genes induced by intracerebral ventricular insulin infusion was impaired in mice with liver-specific STAT3 deficiency or in mice with IL-6 deficiency. |
| 754 | 16581004 | These results thus indicate that IL-6-STAT3 signaling in the liver contributes to insulin action in the brain, leading to the suppression of hepatic glucose production. |
| 755 | 16581004 | Role of hepatic STAT3 in brain-insulin action on hepatic glucose production. |
| 756 | 16581004 | Here, we show that an increase in the plasma insulin concentration, achieved either by glucose administration or by intravenous insulin infusion, stimulates tyrosine phosphorylation of STAT3 in the liver. |
| 757 | 16581004 | This effect of insulin was mediated by the hormone's effects in the brain, and the increase in hepatic IL-6 induced by the brain-insulin action is essential for the activation of STAT3. |
| 758 | 16581004 | The inhibition of hepatic glucose production and of expression of gluconeogenic genes induced by intracerebral ventricular insulin infusion was impaired in mice with liver-specific STAT3 deficiency or in mice with IL-6 deficiency. |
| 759 | 16581004 | These results thus indicate that IL-6-STAT3 signaling in the liver contributes to insulin action in the brain, leading to the suppression of hepatic glucose production. |
| 760 | 16581004 | Role of hepatic STAT3 in brain-insulin action on hepatic glucose production. |
| 761 | 16581004 | Here, we show that an increase in the plasma insulin concentration, achieved either by glucose administration or by intravenous insulin infusion, stimulates tyrosine phosphorylation of STAT3 in the liver. |
| 762 | 16581004 | This effect of insulin was mediated by the hormone's effects in the brain, and the increase in hepatic IL-6 induced by the brain-insulin action is essential for the activation of STAT3. |
| 763 | 16581004 | The inhibition of hepatic glucose production and of expression of gluconeogenic genes induced by intracerebral ventricular insulin infusion was impaired in mice with liver-specific STAT3 deficiency or in mice with IL-6 deficiency. |
| 764 | 16581004 | These results thus indicate that IL-6-STAT3 signaling in the liver contributes to insulin action in the brain, leading to the suppression of hepatic glucose production. |
| 765 | 16581004 | Role of hepatic STAT3 in brain-insulin action on hepatic glucose production. |
| 766 | 16581004 | Here, we show that an increase in the plasma insulin concentration, achieved either by glucose administration or by intravenous insulin infusion, stimulates tyrosine phosphorylation of STAT3 in the liver. |
| 767 | 16581004 | This effect of insulin was mediated by the hormone's effects in the brain, and the increase in hepatic IL-6 induced by the brain-insulin action is essential for the activation of STAT3. |
| 768 | 16581004 | The inhibition of hepatic glucose production and of expression of gluconeogenic genes induced by intracerebral ventricular insulin infusion was impaired in mice with liver-specific STAT3 deficiency or in mice with IL-6 deficiency. |
| 769 | 16581004 | These results thus indicate that IL-6-STAT3 signaling in the liver contributes to insulin action in the brain, leading to the suppression of hepatic glucose production. |
| 770 | 16581004 | Role of hepatic STAT3 in brain-insulin action on hepatic glucose production. |
| 771 | 16581004 | Here, we show that an increase in the plasma insulin concentration, achieved either by glucose administration or by intravenous insulin infusion, stimulates tyrosine phosphorylation of STAT3 in the liver. |
| 772 | 16581004 | This effect of insulin was mediated by the hormone's effects in the brain, and the increase in hepatic IL-6 induced by the brain-insulin action is essential for the activation of STAT3. |
| 773 | 16581004 | The inhibition of hepatic glucose production and of expression of gluconeogenic genes induced by intracerebral ventricular insulin infusion was impaired in mice with liver-specific STAT3 deficiency or in mice with IL-6 deficiency. |
| 774 | 16581004 | These results thus indicate that IL-6-STAT3 signaling in the liver contributes to insulin action in the brain, leading to the suppression of hepatic glucose production. |
| 775 | 16627594 | Long-term administration of estradiol decreases expression of hepatic lipogenic genes and improves insulin sensitivity in ob/ob mice: a possible mechanism is through direct regulation of signal transducer and activator of transcription 3. |
| 776 | 16687413 | AMP-activated protein kinase (AMPK) is a key regulator of cellular energy balance and of the effects of leptin on food intake and fatty acid oxidation. |
| 777 | 16687413 | To determine whether diet-induced obesity (DIO) impairs the AMPK response to leptin in muscle and/or hypothalamus, we fed FVB mice a high fat (55%) diet for 10-12 weeks. |
| 778 | 16687413 | In addition, leptin increased STAT3 phosphorylation 2-fold in arcuate of chow-fed mice, but this effect was attenuated because of elevated basal STAT3 phosphorylation in DIO mice. |
| 779 | 16687413 | Thus, DIO in FVB mice alters alpha2-AMPK in muscle and hypothalamus and STAT3 in hypothalamus and impairs further effects of leptin on these signaling pathways. |
| 780 | 16687413 | Defective responses of AMPK to leptin may contribute to resistance to leptin action on food intake and energy expenditure in obese states. |
| 781 | 16687413 | AMP-activated protein kinase (AMPK) is a key regulator of cellular energy balance and of the effects of leptin on food intake and fatty acid oxidation. |
| 782 | 16687413 | To determine whether diet-induced obesity (DIO) impairs the AMPK response to leptin in muscle and/or hypothalamus, we fed FVB mice a high fat (55%) diet for 10-12 weeks. |
| 783 | 16687413 | In addition, leptin increased STAT3 phosphorylation 2-fold in arcuate of chow-fed mice, but this effect was attenuated because of elevated basal STAT3 phosphorylation in DIO mice. |
| 784 | 16687413 | Thus, DIO in FVB mice alters alpha2-AMPK in muscle and hypothalamus and STAT3 in hypothalamus and impairs further effects of leptin on these signaling pathways. |
| 785 | 16687413 | Defective responses of AMPK to leptin may contribute to resistance to leptin action on food intake and energy expenditure in obese states. |
| 786 | 16721034 | Exercise enhances insulin and leptin signaling in the cerebral cortex and hypothalamus during dexamethasone-induced stress in diabetic rats. |
| 787 | 16721034 | We investigated the modulation of the hypothalamo-pituitary-adrenal (HPA) axis and insulin/leptin signaling associated with glucose utilization in the brains of 90% pancreatectomized diabetic rats, which had been administered two dosages of DEX and exercised for 8 weeks. |
| 788 | 16721034 | The data revealed that the administration of a high dose (0.1 mg/kg body weight/day) of DEX (HDEX) attenuated insulin signaling in the cerebral cortex and hypothalamus, whereas exercise potentiated their insulin signaling along with induction of IRS2 expression. |
| 789 | 16721034 | However, DEX reduced leptin-induced STAT3 phosphorylation in the cortex and hypothalamus, and it increased AMP-activated protein kinase (AMPK) phosphorylation only in the hypothalamus. |
| 790 | 16721034 | Exercise reversed the phosphorylation of STAT3 and AMPK which had been modulated by DEX. |
| 791 | 16721034 | In conclusion, exercise improves insulin and leptin signaling in the cerebral cortex and hypothalamus of diabetic rats exacerbated with HDEX, contributing to the regulation of body weight and glucose homeostasis. |
| 792 | 16721034 | Exercise enhances insulin and leptin signaling in the cerebral cortex and hypothalamus during dexamethasone-induced stress in diabetic rats. |
| 793 | 16721034 | We investigated the modulation of the hypothalamo-pituitary-adrenal (HPA) axis and insulin/leptin signaling associated with glucose utilization in the brains of 90% pancreatectomized diabetic rats, which had been administered two dosages of DEX and exercised for 8 weeks. |
| 794 | 16721034 | The data revealed that the administration of a high dose (0.1 mg/kg body weight/day) of DEX (HDEX) attenuated insulin signaling in the cerebral cortex and hypothalamus, whereas exercise potentiated their insulin signaling along with induction of IRS2 expression. |
| 795 | 16721034 | However, DEX reduced leptin-induced STAT3 phosphorylation in the cortex and hypothalamus, and it increased AMP-activated protein kinase (AMPK) phosphorylation only in the hypothalamus. |
| 796 | 16721034 | Exercise reversed the phosphorylation of STAT3 and AMPK which had been modulated by DEX. |
| 797 | 16721034 | In conclusion, exercise improves insulin and leptin signaling in the cerebral cortex and hypothalamus of diabetic rats exacerbated with HDEX, contributing to the regulation of body weight and glucose homeostasis. |
| 798 | 16730240 | The mRNA levels of three members of the family of signal transducers and activators of transcription, STAT1, STAT3 and STAT5b, were also increased 2-4 times. |
| 799 | 16751422 | We report in this study that leptin receptor (ObR) is expressed on resting normal mouse CD4(+), CD8(+), B cells, and monocyte/macrophages. |
| 800 | 16751422 | Leptin binding to ObR results in increased STAT-3 activation in T cells, with a different activation pattern in resting vs anti-CD3 Ab stimulated T cells. |
| 801 | 16751422 | B lymphocytes appear to be more susceptible to the antiapoptotic effects of leptin, and they show higher surface expression of ObR, compared with T cells. |
| 802 | 16751422 | Moreover, CD4(+) T cells isolated from ObR-deficient mice displayed a reduced proliferative response, compared with normal controls. |
| 803 | 16751422 | Furthermore, ObR/STAT-3-mediated signaling in T lymphocytes is decreased in the diet-induced obese mouse model of obesity and leptin resistance. |
| 804 | 16751422 | In summary, our findings show that the ObR is expressed on normal mouse lymphocyte subsets, that leptin plays a role in lymphocyte survival, and that leptin alters the ObR/STAT-3-mediated signaling in T cells. |
| 805 | 16751422 | We report in this study that leptin receptor (ObR) is expressed on resting normal mouse CD4(+), CD8(+), B cells, and monocyte/macrophages. |
| 806 | 16751422 | Leptin binding to ObR results in increased STAT-3 activation in T cells, with a different activation pattern in resting vs anti-CD3 Ab stimulated T cells. |
| 807 | 16751422 | B lymphocytes appear to be more susceptible to the antiapoptotic effects of leptin, and they show higher surface expression of ObR, compared with T cells. |
| 808 | 16751422 | Moreover, CD4(+) T cells isolated from ObR-deficient mice displayed a reduced proliferative response, compared with normal controls. |
| 809 | 16751422 | Furthermore, ObR/STAT-3-mediated signaling in T lymphocytes is decreased in the diet-induced obese mouse model of obesity and leptin resistance. |
| 810 | 16751422 | In summary, our findings show that the ObR is expressed on normal mouse lymphocyte subsets, that leptin plays a role in lymphocyte survival, and that leptin alters the ObR/STAT-3-mediated signaling in T cells. |
| 811 | 16751422 | We report in this study that leptin receptor (ObR) is expressed on resting normal mouse CD4(+), CD8(+), B cells, and monocyte/macrophages. |
| 812 | 16751422 | Leptin binding to ObR results in increased STAT-3 activation in T cells, with a different activation pattern in resting vs anti-CD3 Ab stimulated T cells. |
| 813 | 16751422 | B lymphocytes appear to be more susceptible to the antiapoptotic effects of leptin, and they show higher surface expression of ObR, compared with T cells. |
| 814 | 16751422 | Moreover, CD4(+) T cells isolated from ObR-deficient mice displayed a reduced proliferative response, compared with normal controls. |
| 815 | 16751422 | Furthermore, ObR/STAT-3-mediated signaling in T lymphocytes is decreased in the diet-induced obese mouse model of obesity and leptin resistance. |
| 816 | 16751422 | In summary, our findings show that the ObR is expressed on normal mouse lymphocyte subsets, that leptin plays a role in lymphocyte survival, and that leptin alters the ObR/STAT-3-mediated signaling in T cells. |
| 817 | 16876574 | Adipose tissue secretes leptin, steroid hormones, adiponectin, inflammatory cytokines, resistin, complement factors, and vasoactive peptides. |
| 818 | 16876574 | Leptin activates Janus-activating kinase2 (Jak2) and STAT 3, resulting in stimulation of anorexigenic peptides, e.g., alpha-MSH and CART, and inhibition of orexigenic peptides, e.g., NPY and AGRP. |
| 819 | 16876574 | Leptin also stimulates fatty acid oxidation, insulin release, and peripheral insulin action. |
| 820 | 16876574 | These effects involve regulation of PI-3 kinase, PTP-1B, suppressor of cytokine signaling-3 (SOCS-3), and AMP-activated protein kinase in the brain and peripheral organs. |
| 821 | 16876574 | There is emerging evidence that leptin, adiponectin, and resistin act through overlapping pathways. |
| 822 | 16926159 | Pyrrolidine dithiocarbamate inhibits interleukin-6 signaling through impaired STAT3 activation and association with transcriptional coactivators in hepatocytes. |
| 823 | 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. |
| 824 | 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. |
| 825 | 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. |
| 826 | 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. |
| 827 | 16926159 | Importantly, treatment of HepG2 cells and a primary culture of rat hepatocytes with PDTC restored insulin responsiveness that was abrogated by IL-6. |
| 828 | 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. |
| 829 | 16926159 | Pyrrolidine dithiocarbamate inhibits interleukin-6 signaling through impaired STAT3 activation and association with transcriptional coactivators in hepatocytes. |
| 830 | 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. |
| 831 | 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. |
| 832 | 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. |
| 833 | 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. |
| 834 | 16926159 | Importantly, treatment of HepG2 cells and a primary culture of rat hepatocytes with PDTC restored insulin responsiveness that was abrogated by IL-6. |
| 835 | 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. |
| 836 | 16926159 | Pyrrolidine dithiocarbamate inhibits interleukin-6 signaling through impaired STAT3 activation and association with transcriptional coactivators in hepatocytes. |
| 837 | 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. |
| 838 | 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. |
| 839 | 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. |
| 840 | 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. |
| 841 | 16926159 | Importantly, treatment of HepG2 cells and a primary culture of rat hepatocytes with PDTC restored insulin responsiveness that was abrogated by IL-6. |
| 842 | 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. |
| 843 | 16926159 | Pyrrolidine dithiocarbamate inhibits interleukin-6 signaling through impaired STAT3 activation and association with transcriptional coactivators in hepatocytes. |
| 844 | 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. |
| 845 | 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. |
| 846 | 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. |
| 847 | 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. |
| 848 | 16926159 | Importantly, treatment of HepG2 cells and a primary culture of rat hepatocytes with PDTC restored insulin responsiveness that was abrogated by IL-6. |
| 849 | 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. |
| 850 | 16926159 | Pyrrolidine dithiocarbamate inhibits interleukin-6 signaling through impaired STAT3 activation and association with transcriptional coactivators in hepatocytes. |
| 851 | 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. |
| 852 | 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. |
| 853 | 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. |
| 854 | 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. |
| 855 | 16926159 | Importantly, treatment of HepG2 cells and a primary culture of rat hepatocytes with PDTC restored insulin responsiveness that was abrogated by IL-6. |
| 856 | 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. |
| 857 | 16926159 | Pyrrolidine dithiocarbamate inhibits interleukin-6 signaling through impaired STAT3 activation and association with transcriptional coactivators in hepatocytes. |
| 858 | 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. |
| 859 | 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. |
| 860 | 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. |
| 861 | 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. |
| 862 | 16926159 | Importantly, treatment of HepG2 cells and a primary culture of rat hepatocytes with PDTC restored insulin responsiveness that was abrogated by IL-6. |
| 863 | 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. |
| 864 | 16965293 | Young adult-specific hyperphagia in diabetic Goto-kakizaki rats is associated with leptin resistance and elevation of neuropeptide Y mRNA in the arcuate nucleus. |
| 865 | 16965293 | In GK rats, leptin-induced phosphorylation of signal transducer and activator of transcription 3 was significantly reduced in the cells of the hypothalamic arcuate nucleus (ARC), but not of the ventromedial hypothalamus, whereas the mRNA level of functional leptin receptor was unaltered. |
| 866 | 16965293 | By real-time polymerase chain reaction and in situ hybridisation, mRNA levels of neuropeptide Y, but not pro-opiomelanocortin and galanin-like peptide, were significantly increased in the ARC of GK rats at 11 weeks, but not 26 weeks. |
| 867 | 16965293 | These results demonstrate that young adult GK rats display hyperphagia in association with leptin resistance and increased NPY mRNA level in the ARC. |
| 868 | 17021368 | Using "reporter" mice, in which LRb-expressing (long form of the leptin receptor) neurons express the histological marker, beta-galactosidase, coupled with the detection of LRb-mediated signal transducer and activator of transcription 3 signaling events, we identified LRb expression in neuronal populations both within and outside the hypothalamus. |
| 869 | 17021375 | Leptin activates tyrosine kinase, Janus kinase 2, and signal transducer and activator of transcription 3, leading to increased levels of anorexigenic peptides, e.g., alpha-melanocyte stimulating hormone and cocaine- and amphetamine-regulated transcript, and inhibition of orexigenic peptides, e.g., neuropeptide Y and agouti-related peptide. |
| 870 | 17021375 | Obesity is characterized by hyperleptinemia and hypothalamic leptin resistance, partly caused by induction of suppressor of cytokine signaling-3. |
| 871 | 17021375 | Leptin also decreases glucose and stimulates lipolysis through central and peripheral pathways involving AMP-activated protein kinase (AMPK). |
| 872 | 17021375 | Obesity, diabetes, and atherosclerosis have been associated with reduced adiponectin levels, whereas adiponectin treatment reverses these abnormalities partly through activation of AMPK in liver and muscle. |
| 873 | 17021375 | Administration of adiponectin in the brain recapitulates the peripheral actions to increase fatty acid oxidation and insulin sensitivity and reduce glucose. |
| 874 | 17021375 | As with leptin, adiponectin requires the central melanocortin pathway. |
| 875 | 17021375 | Furthermore, adiponectin stimulates fatty acid oxidation and reduces glucose and lipids, at least in part, by activating AMPK in muscle and liver. |
| 876 | 17023536 | Inactivation of signal transducer and activator of transcription 3 in proopiomelanocortin (Pomc) neurons causes decreased pomc expression, mild obesity, and defects in compensatory refeeding. |
| 877 | 17023536 | Leptin is an adipocyte-derived hormone that signals body energy status to the brain by acting on multiple neuronal subgroups in the hypothalamus, including those that express proopiomelanocortin (Pomc) and agouti-related protein (Agrp). |
| 878 | 17023536 | Signal transducer and activator of transcription 3 (Stat3) is an important intracellular signaling molecule activated by leptin, and previous studies have shown that mice carrying a mutated leptin receptor that abolished Stat3 binding are grossly obese. |
| 879 | 17023536 | To determine the extent to which Stat3 signaling in Pomc neurons was responsible for these effects, we constructed Pomc-specific Stat3 mutants using a Cre recombinase transgene driven by the Pomc promoter. |
| 880 | 17023536 | We find that Pomc expression is diminished in the mutant mice, suggesting that Stat3 is required for Pomc transcription. |
| 881 | 17023536 | These results demonstrate a requirement for Stat3 in transcriptional regulation of Pomc but indicate that this circuit is only one of several components that underlie the neuronal response to leptin and the role of Stat3 in that response. |
| 882 | 17023536 | Inactivation of signal transducer and activator of transcription 3 in proopiomelanocortin (Pomc) neurons causes decreased pomc expression, mild obesity, and defects in compensatory refeeding. |
| 883 | 17023536 | Leptin is an adipocyte-derived hormone that signals body energy status to the brain by acting on multiple neuronal subgroups in the hypothalamus, including those that express proopiomelanocortin (Pomc) and agouti-related protein (Agrp). |
| 884 | 17023536 | Signal transducer and activator of transcription 3 (Stat3) is an important intracellular signaling molecule activated by leptin, and previous studies have shown that mice carrying a mutated leptin receptor that abolished Stat3 binding are grossly obese. |
| 885 | 17023536 | To determine the extent to which Stat3 signaling in Pomc neurons was responsible for these effects, we constructed Pomc-specific Stat3 mutants using a Cre recombinase transgene driven by the Pomc promoter. |
| 886 | 17023536 | We find that Pomc expression is diminished in the mutant mice, suggesting that Stat3 is required for Pomc transcription. |
| 887 | 17023536 | These results demonstrate a requirement for Stat3 in transcriptional regulation of Pomc but indicate that this circuit is only one of several components that underlie the neuronal response to leptin and the role of Stat3 in that response. |
| 888 | 17023536 | Inactivation of signal transducer and activator of transcription 3 in proopiomelanocortin (Pomc) neurons causes decreased pomc expression, mild obesity, and defects in compensatory refeeding. |
| 889 | 17023536 | Leptin is an adipocyte-derived hormone that signals body energy status to the brain by acting on multiple neuronal subgroups in the hypothalamus, including those that express proopiomelanocortin (Pomc) and agouti-related protein (Agrp). |
| 890 | 17023536 | Signal transducer and activator of transcription 3 (Stat3) is an important intracellular signaling molecule activated by leptin, and previous studies have shown that mice carrying a mutated leptin receptor that abolished Stat3 binding are grossly obese. |
| 891 | 17023536 | To determine the extent to which Stat3 signaling in Pomc neurons was responsible for these effects, we constructed Pomc-specific Stat3 mutants using a Cre recombinase transgene driven by the Pomc promoter. |
| 892 | 17023536 | We find that Pomc expression is diminished in the mutant mice, suggesting that Stat3 is required for Pomc transcription. |
| 893 | 17023536 | These results demonstrate a requirement for Stat3 in transcriptional regulation of Pomc but indicate that this circuit is only one of several components that underlie the neuronal response to leptin and the role of Stat3 in that response. |
| 894 | 17023536 | Inactivation of signal transducer and activator of transcription 3 in proopiomelanocortin (Pomc) neurons causes decreased pomc expression, mild obesity, and defects in compensatory refeeding. |
| 895 | 17023536 | Leptin is an adipocyte-derived hormone that signals body energy status to the brain by acting on multiple neuronal subgroups in the hypothalamus, including those that express proopiomelanocortin (Pomc) and agouti-related protein (Agrp). |
| 896 | 17023536 | Signal transducer and activator of transcription 3 (Stat3) is an important intracellular signaling molecule activated by leptin, and previous studies have shown that mice carrying a mutated leptin receptor that abolished Stat3 binding are grossly obese. |
| 897 | 17023536 | To determine the extent to which Stat3 signaling in Pomc neurons was responsible for these effects, we constructed Pomc-specific Stat3 mutants using a Cre recombinase transgene driven by the Pomc promoter. |
| 898 | 17023536 | We find that Pomc expression is diminished in the mutant mice, suggesting that Stat3 is required for Pomc transcription. |
| 899 | 17023536 | These results demonstrate a requirement for Stat3 in transcriptional regulation of Pomc but indicate that this circuit is only one of several components that underlie the neuronal response to leptin and the role of Stat3 in that response. |
| 900 | 17023536 | Inactivation of signal transducer and activator of transcription 3 in proopiomelanocortin (Pomc) neurons causes decreased pomc expression, mild obesity, and defects in compensatory refeeding. |
| 901 | 17023536 | Leptin is an adipocyte-derived hormone that signals body energy status to the brain by acting on multiple neuronal subgroups in the hypothalamus, including those that express proopiomelanocortin (Pomc) and agouti-related protein (Agrp). |
| 902 | 17023536 | Signal transducer and activator of transcription 3 (Stat3) is an important intracellular signaling molecule activated by leptin, and previous studies have shown that mice carrying a mutated leptin receptor that abolished Stat3 binding are grossly obese. |
| 903 | 17023536 | To determine the extent to which Stat3 signaling in Pomc neurons was responsible for these effects, we constructed Pomc-specific Stat3 mutants using a Cre recombinase transgene driven by the Pomc promoter. |
| 904 | 17023536 | We find that Pomc expression is diminished in the mutant mice, suggesting that Stat3 is required for Pomc transcription. |
| 905 | 17023536 | These results demonstrate a requirement for Stat3 in transcriptional regulation of Pomc but indicate that this circuit is only one of several components that underlie the neuronal response to leptin and the role of Stat3 in that response. |
| 906 | 17038325 | Combined leptin actions on adipose tissue and hypothalamus are required to deplete adipocyte fat in lean rats: implications for obesity treatment. |
| 907 | 17038325 | In +/+ but not in fa/fa rats, plasma catecholamine levels rose, and both P-STAT3 and P-CREB increased in adipose tissue, suggesting that both direct and indirect (hypothalamic) leptin receptor-mediated actions of hyperleptinemia are involved in depletion of adipocyte fat. |
| 908 | 17063460 | Molecular determinants of FGF-21 activity-synergy and cross-talk with PPARgamma signaling. |
| 909 | 17063460 | Here we describe the early signaling events triggered by FGF-21 treatment of 3T3-L1 adipocytes and reveal a functional interplay between FGF-21 and peroxisome proliferator-activated receptor gamma (PPARgamma) pathways that leads to a marked stimulation of glucose transport. |
| 910 | 17063460 | While the early actions of FGF-21 on 3T3-L1 adipocytes involve rapid accumulation of intracellular calcium and phosphorylation of Akt, GSK-3, p70(S6K), SHP-2, MEK1/2, and Stat3, continuous treatment for 72 h induces an increase in PPARgamma protein expression. |
| 911 | 17063460 | Moreover, chronic activation of the PPARgamma pathway in 3T3-L1 adipocytes with the PPARgamma agonist and anti-diabetic agent, rosiglitazone (BRL 49653), enhances FGF-21 action to induce tyrosine phosphorylation of FGF receptor-2. |
| 912 | 17063460 | Strikingly, treatment of cells with FGF-21 and rosiglitazone in combination leads to a pronounced increase in expression of the GLUT1 glucose transporter and a marked synergy in stimulation of glucose transport. |
| 913 | 17063460 | Together these results reveal a novel synergy between two regulators of glucose homeostasis, FGF-21 and PPARgamma, and further define FGF-21 mechanism of action. |
| 914 | 17065390 | Here, we report the establishment of the first in vitro tissue model of INGAP expression that consists of epithelial cystic structures derived from hamster pancreatic acinar tissue cultured in collagen matrix. |
| 915 | 17065390 | We also demonstrate for the first time that INGAP gene expression was significantly induced by treatment with interleukin (IL)-6 and further enhanced by a combination of IL-6 with dexamethazone and nicotinamide. |
| 916 | 17065390 | Additionally, our data suggest that the effect of IL-6 on INGAP expression is mediated via the JAK/STAT3 signaling pathway. |
| 917 | 17143592 | In contrast to our previous findings with MDA-MB-435 cells, DFMO did not affect the activation of STAT3, JNK, and ERK, but decreased phosphorylation of p38. |
| 918 | 17192474 | The GSK3beta mediators, P-Akt, P-extracellular signal-related kinase (ERK)1, and P-signal transducer and activator of transcription (STAT)3, were also significantly reduced in untreated DBR compared with NDBR rats. |
| 919 | 17205581 | Socs 3 modulates the activity of the transcription factor Stat3 in mammary tissue and controls alveolar homeostasis. |
| 920 | 17205581 | Signal transducer and activator of transcription 5 and 3 (Stat5 and Stat3) control pregnancy-mediated mammary development and involution-dependent remodeling, respectively. |
| 921 | 17205581 | Suppressor of cytokine signaling 3 (Socs3) has been implicated in the modulation of both Stat3 and Stat5 activity. |
| 922 | 17205581 | Loss of Socs3 led to enhanced and precocious Stat3 activation. |
| 923 | 17205581 | Thus, Socs3 serves as a modulator of Stat3 activity to ensure controlled proliferation and apoptosis in pregnancy and involution, respectively. |
| 924 | 17205581 | Socs 3 modulates the activity of the transcription factor Stat3 in mammary tissue and controls alveolar homeostasis. |
| 925 | 17205581 | Signal transducer and activator of transcription 5 and 3 (Stat5 and Stat3) control pregnancy-mediated mammary development and involution-dependent remodeling, respectively. |
| 926 | 17205581 | Suppressor of cytokine signaling 3 (Socs3) has been implicated in the modulation of both Stat3 and Stat5 activity. |
| 927 | 17205581 | Loss of Socs3 led to enhanced and precocious Stat3 activation. |
| 928 | 17205581 | Thus, Socs3 serves as a modulator of Stat3 activity to ensure controlled proliferation and apoptosis in pregnancy and involution, respectively. |
| 929 | 17205581 | Socs 3 modulates the activity of the transcription factor Stat3 in mammary tissue and controls alveolar homeostasis. |
| 930 | 17205581 | Signal transducer and activator of transcription 5 and 3 (Stat5 and Stat3) control pregnancy-mediated mammary development and involution-dependent remodeling, respectively. |
| 931 | 17205581 | Suppressor of cytokine signaling 3 (Socs3) has been implicated in the modulation of both Stat3 and Stat5 activity. |
| 932 | 17205581 | Loss of Socs3 led to enhanced and precocious Stat3 activation. |
| 933 | 17205581 | Thus, Socs3 serves as a modulator of Stat3 activity to ensure controlled proliferation and apoptosis in pregnancy and involution, respectively. |
| 934 | 17205581 | Socs 3 modulates the activity of the transcription factor Stat3 in mammary tissue and controls alveolar homeostasis. |
| 935 | 17205581 | Signal transducer and activator of transcription 5 and 3 (Stat5 and Stat3) control pregnancy-mediated mammary development and involution-dependent remodeling, respectively. |
| 936 | 17205581 | Suppressor of cytokine signaling 3 (Socs3) has been implicated in the modulation of both Stat3 and Stat5 activity. |
| 937 | 17205581 | Loss of Socs3 led to enhanced and precocious Stat3 activation. |
| 938 | 17205581 | Thus, Socs3 serves as a modulator of Stat3 activity to ensure controlled proliferation and apoptosis in pregnancy and involution, respectively. |
| 939 | 17205581 | Socs 3 modulates the activity of the transcription factor Stat3 in mammary tissue and controls alveolar homeostasis. |
| 940 | 17205581 | Signal transducer and activator of transcription 5 and 3 (Stat5 and Stat3) control pregnancy-mediated mammary development and involution-dependent remodeling, respectively. |
| 941 | 17205581 | Suppressor of cytokine signaling 3 (Socs3) has been implicated in the modulation of both Stat3 and Stat5 activity. |
| 942 | 17205581 | Loss of Socs3 led to enhanced and precocious Stat3 activation. |
| 943 | 17205581 | Thus, Socs3 serves as a modulator of Stat3 activity to ensure controlled proliferation and apoptosis in pregnancy and involution, respectively. |
| 944 | 17267401 | Insulin antagonizes interleukin-6 signaling and is anti-inflammatory in 3T3-L1 adipocytes. |
| 945 | 17267401 | Adipose tissue secretes different adipokines, including interleukin-6 (IL-6), that have been implicated in the insulin resistance and inflammatory state characterizing obesity. |
| 946 | 17267401 | We examined the putative cross-talk between insulin and IL-6 in adipose cells and found that insulin exerts an inhibitory effect on the IL-6 signaling pathway by altering the post-translational modifications of the signal transducer and activator of transcription 3 (STAT3). |
| 947 | 17267401 | Insulin reduces the tyrosine phosphorylation and increases the serine phosphorylation of STAT3, thereby reducing its nuclear localization and transcriptional activity. |
| 948 | 17267401 | Signaling through the MEK/MAPK pathway plays an important role as treatment with the MEK inhibitor PD98059 reduces the effects of insulin on IL-6 signaling. |
| 949 | 17267401 | We also show that the protein tyrosine phosphatase SHP2 is activated upon insulin signaling and is required for the dephosphorylation of STAT3 and that insulin exerts a synergistic effect with IL-6 on suppressor of cytokine signaling 3 expression. |
| 950 | 17267401 | As a consequence, the IL-6-induced expression of the inflammatory markers serum amyloid A 3 and haptoglobin are significantly decreased in cells incubated with both IL-6 and insulin. |
| 951 | 17267401 | Thus, insulin exerts an important anti-inflammatory effect in adipose cells by impairing the IL-6 signal at several levels. |
| 952 | 17267401 | Insulin antagonizes interleukin-6 signaling and is anti-inflammatory in 3T3-L1 adipocytes. |
| 953 | 17267401 | Adipose tissue secretes different adipokines, including interleukin-6 (IL-6), that have been implicated in the insulin resistance and inflammatory state characterizing obesity. |
| 954 | 17267401 | We examined the putative cross-talk between insulin and IL-6 in adipose cells and found that insulin exerts an inhibitory effect on the IL-6 signaling pathway by altering the post-translational modifications of the signal transducer and activator of transcription 3 (STAT3). |
| 955 | 17267401 | Insulin reduces the tyrosine phosphorylation and increases the serine phosphorylation of STAT3, thereby reducing its nuclear localization and transcriptional activity. |
| 956 | 17267401 | Signaling through the MEK/MAPK pathway plays an important role as treatment with the MEK inhibitor PD98059 reduces the effects of insulin on IL-6 signaling. |
| 957 | 17267401 | We also show that the protein tyrosine phosphatase SHP2 is activated upon insulin signaling and is required for the dephosphorylation of STAT3 and that insulin exerts a synergistic effect with IL-6 on suppressor of cytokine signaling 3 expression. |
| 958 | 17267401 | As a consequence, the IL-6-induced expression of the inflammatory markers serum amyloid A 3 and haptoglobin are significantly decreased in cells incubated with both IL-6 and insulin. |
| 959 | 17267401 | Thus, insulin exerts an important anti-inflammatory effect in adipose cells by impairing the IL-6 signal at several levels. |
| 960 | 17267401 | Insulin antagonizes interleukin-6 signaling and is anti-inflammatory in 3T3-L1 adipocytes. |
| 961 | 17267401 | Adipose tissue secretes different adipokines, including interleukin-6 (IL-6), that have been implicated in the insulin resistance and inflammatory state characterizing obesity. |
| 962 | 17267401 | We examined the putative cross-talk between insulin and IL-6 in adipose cells and found that insulin exerts an inhibitory effect on the IL-6 signaling pathway by altering the post-translational modifications of the signal transducer and activator of transcription 3 (STAT3). |
| 963 | 17267401 | Insulin reduces the tyrosine phosphorylation and increases the serine phosphorylation of STAT3, thereby reducing its nuclear localization and transcriptional activity. |
| 964 | 17267401 | Signaling through the MEK/MAPK pathway plays an important role as treatment with the MEK inhibitor PD98059 reduces the effects of insulin on IL-6 signaling. |
| 965 | 17267401 | We also show that the protein tyrosine phosphatase SHP2 is activated upon insulin signaling and is required for the dephosphorylation of STAT3 and that insulin exerts a synergistic effect with IL-6 on suppressor of cytokine signaling 3 expression. |
| 966 | 17267401 | As a consequence, the IL-6-induced expression of the inflammatory markers serum amyloid A 3 and haptoglobin are significantly decreased in cells incubated with both IL-6 and insulin. |
| 967 | 17267401 | Thus, insulin exerts an important anti-inflammatory effect in adipose cells by impairing the IL-6 signal at several levels. |
| 968 | 17295835 | The dual function of hepatic SOCS3 in insulin resistance in vivo. |
| 969 | 17295835 | The suppressor of cytokine signaling 3 (SOCS3), which is induced by pro-inflammatory cytokines, such as TNFalpha and IL-6, has been implicated in inflammation-mediated insulin resistance in the liver and adipocytes. |
| 970 | 17295835 | However, no genetic evidence has been provided for the involvement of SOCS3 on insulin resistance. |
| 971 | 17295835 | Here, we generated hepatocyte-specific SOCS3-deficient (L-SOCS3 cKO) mice and examined insulin sensitivity. |
| 972 | 17295835 | Being consistent with a previous idea, the loss of SOCS3 in the liver apparently improved insulin sensitivity. |
| 973 | 17295835 | However, unexpectedly, L-SOCS3 cKO mice exhibited obesity and systemic insulin resistance with age. |
| 974 | 17295835 | Insulin signaling was rather suppressed in muscles, suggesting that deletion of the SOCS3 gene in the liver modulates insulin sensitivity in other organs. |
| 975 | 17295835 | Anti-inflammatory reagent, sodium salicylate, partial improved insulin resistance of aged L-SOCS3 cKO mice, suggesting that enhanced inflammatory status is associated with the phenotype of these mice. |
| 976 | 17295835 | STAT3 was hyperactivated and acute-phase proteins were elevated in L-SOCS3 cKO mice liver, which were reduced by sodium salicylate treatment. |
| 977 | 17295835 | We conclude that hepatic SOCS3 is a mediator of insulin resistance in the liver; however, lack of SOCS3 in the liver promotes systemic insulin resistance by mimicking chronic inflammation. |
| 978 | 17327450 | Effects of pioglitazone on suppressor of cytokine signaling 3 expression: potential mechanisms for its effects on insulin sensitivity and adiponectin expression. |
| 979 | 17327450 | Recent studies have shown that the induction of suppressor of cytokine signaling 3 (SOCS3) is related to the development of insulin resistance. |
| 980 | 17327450 | Here, we examined whether the insulin-sensitizing effect of pioglitazone affects the SOCS induction. |
| 981 | 17327450 | In 3T3-L1 adipocytes, mediators of insulin resistance such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6, growth hormone, and insulin increased SOCS3 expression, which was partially inhibited by pioglitazone. |
| 982 | 17327450 | The ability of pioglitazone to suppress SOCS3 induction by TNF-alpha was greatly augmented by peroxisome proliferator-activated receptor gamma overexpression. |
| 983 | 17327450 | SOCS3 overexpression and tyrphostin AG490, a Janus kinase 2 inhibitor, or dominant-negative STAT3 expression partially inhibited adiponectin secretion and was accompanied by decreased STAT3 phosphorylation. |
| 984 | 17327450 | Conversely, pioglitazone increased adiponectin secretion and STAT3 phosphorylation in fat tissue of db/db mice and in 3T3-L1 adipocytes. |
| 985 | 17327450 | These results suggest that pioglitazone exerts its effect to improve whole-body insulin sensitivity in part through the suppression of SOCS3, which is associated with the increase in STAT3 phosphorylation and adiponectin production in fat tissue. |
| 986 | 17327450 | Effects of pioglitazone on suppressor of cytokine signaling 3 expression: potential mechanisms for its effects on insulin sensitivity and adiponectin expression. |
| 987 | 17327450 | Recent studies have shown that the induction of suppressor of cytokine signaling 3 (SOCS3) is related to the development of insulin resistance. |
| 988 | 17327450 | Here, we examined whether the insulin-sensitizing effect of pioglitazone affects the SOCS induction. |
| 989 | 17327450 | In 3T3-L1 adipocytes, mediators of insulin resistance such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6, growth hormone, and insulin increased SOCS3 expression, which was partially inhibited by pioglitazone. |
| 990 | 17327450 | The ability of pioglitazone to suppress SOCS3 induction by TNF-alpha was greatly augmented by peroxisome proliferator-activated receptor gamma overexpression. |
| 991 | 17327450 | SOCS3 overexpression and tyrphostin AG490, a Janus kinase 2 inhibitor, or dominant-negative STAT3 expression partially inhibited adiponectin secretion and was accompanied by decreased STAT3 phosphorylation. |
| 992 | 17327450 | Conversely, pioglitazone increased adiponectin secretion and STAT3 phosphorylation in fat tissue of db/db mice and in 3T3-L1 adipocytes. |
| 993 | 17327450 | These results suggest that pioglitazone exerts its effect to improve whole-body insulin sensitivity in part through the suppression of SOCS3, which is associated with the increase in STAT3 phosphorylation and adiponectin production in fat tissue. |
| 994 | 17327450 | Effects of pioglitazone on suppressor of cytokine signaling 3 expression: potential mechanisms for its effects on insulin sensitivity and adiponectin expression. |
| 995 | 17327450 | Recent studies have shown that the induction of suppressor of cytokine signaling 3 (SOCS3) is related to the development of insulin resistance. |
| 996 | 17327450 | Here, we examined whether the insulin-sensitizing effect of pioglitazone affects the SOCS induction. |
| 997 | 17327450 | In 3T3-L1 adipocytes, mediators of insulin resistance such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6, growth hormone, and insulin increased SOCS3 expression, which was partially inhibited by pioglitazone. |
| 998 | 17327450 | The ability of pioglitazone to suppress SOCS3 induction by TNF-alpha was greatly augmented by peroxisome proliferator-activated receptor gamma overexpression. |
| 999 | 17327450 | SOCS3 overexpression and tyrphostin AG490, a Janus kinase 2 inhibitor, or dominant-negative STAT3 expression partially inhibited adiponectin secretion and was accompanied by decreased STAT3 phosphorylation. |
| 1000 | 17327450 | Conversely, pioglitazone increased adiponectin secretion and STAT3 phosphorylation in fat tissue of db/db mice and in 3T3-L1 adipocytes. |
| 1001 | 17327450 | These results suggest that pioglitazone exerts its effect to improve whole-body insulin sensitivity in part through the suppression of SOCS3, which is associated with the increase in STAT3 phosphorylation and adiponectin production in fat tissue. |
| 1002 | 17363741 | Interleukin (IL)-6 is a proinflammatory cytokine shown to modify insulin sensitivity. |
| 1003 | 17363741 | Elevated plasma levels of IL-6 are observed in insulin-resistant states. |
| 1004 | 17363741 | Thus, IL-6 has also been suggested to promote insulin-mediated glucose utilization. |
| 1005 | 17363741 | A 30-min pre-exposure to IL-6 did not affect insulin-stimulated glucose transport. |
| 1006 | 17363741 | IL-6 increased phosphorylation of STAT3 (signal transducer and activator of transcription 3; P < 0.05), AMP-activated protein kinase (P = 0.063), and p38 mitogen-activated protein kinase (P < 0.05) and reduced phosphorylation of S6 ribosomal protein (P < 0.05). |
| 1007 | 17363741 | In contrast, phosphorylation of protein kinase B/Akt, AS160 (Akt substrate of 160 kDa), and GSK3alpha/beta (glycogen synthase kinase 3alpha/beta) as well as insulin receptor substrate 1-associated phosphatidylinositol 3-kinase activity remained unaltered. |
| 1008 | 17363741 | Insulin-stimulated glucose transport and insulin signaling were unchanged after IL-6 exposure. |
| 1009 | 17394460 | Rosiglitazone treatment curtailed the post-ischemic expression of the pro-inflammatory genes interleukin-1beta, interleukin-6, macrophage inflammatory protein-1alpha, monocyte chemoattractant protein-1, cyclooxygenase-2, inducible nitric oxide synthase, early growth response-1, CCAAT/enhancer binding protein-beta and nuclear factor-kappa B, and increased the expression of the anti-oxidant enzymes catalase and copper/zinc-superoxide dismutase. |
| 1010 | 17394460 | Rosiglitazone also increased the expression of the anti-inflammatory gene suppressor of cytokine signaling-3 and prevented the phosphorylation of the transcription factor signal transducer and activator of transcription-3 after focal ischemia. |
| 1011 | 17406644 | Glycerol kinase deficiency alters expression of genes involved in lipid metabolism, carbohydrate metabolism, and insulin signaling. |
| 1012 | 17406644 | Glycerol kinase (GK) is at the interface of fat and carbohydrate metabolism and has been implicated in insulin resistance and type 2 diabetes mellitus. |
| 1013 | 17406644 | To define GK's role in insulin resistance, we examined gene expression in brown adipose tissue in a glycerol kinase knockout (KO) mouse model using microarray analysis. |
| 1014 | 17406644 | PathwayAssist analysis confirmed direct and indirect connections between glycerol kinase and genes in lipid metabolism, carbohydrate metabolism, insulin signaling, and insulin resistance. |
| 1015 | 17406644 | Network component analysis (NCA) showed that the transcription factors (TFs) PPAR-gamma, SREBP-1, SREBP-2, STAT3, STAT5, SP1, CEBPalpha, CREB, GR and PPAR-alpha have altered activity in the KO mice. |
| 1016 | 17406644 | This study elucidates the complex network of glycerol kinase and further confirms a possible role for glycerol kinase deficiency, a simple Mendelian disorder, in insulin resistance, and type 2 diabetes mellitus, a common complex genetic disorder. |
| 1017 | 17440173 | CD36-facilitated fatty acid uptake inhibits leptin production and signaling in adipose tissue. |
| 1018 | 17440173 | Fatty acid inhibition of basal and insulin-stimulated leptin release is linked to CD36-facilitated fatty acid flux, which is important for fatty acid activation of peroxisome proliferator-activated receptor gamma and likely contributes to the nutrient sensing function of adipocytes. |
| 1019 | 17440173 | Fatty acid uptake also may modulate adipocyte leptin signaling. |
| 1020 | 17440173 | The ratio of phosphorylated to unphosphorylated signal transducer and activator of transcription 3, an index of leptin activity, is increased in CD36-null fat tissue disproportionately to leptin levels. |
| 1021 | 17440173 | Targeting adipocyte CD36 may offer a way to uncouple leptin production and adiposity. |
| 1022 | 17526654 | Angiotensin II and endothelin-1 augment the vascular complications of diabetes via JAK2 activation. |
| 1023 | 17526654 | The JAK/STAT pathway is activated in vitro by angiotensin II (ANG II) and endothelin-1 (ET-1), which are implicated in the development of diabetic complications. |
| 1024 | 17526654 | We hypothesized that ANG II and ET-1 activate the JAK/STAT pathway in vivo to participate in the development of diabetic vascular complications. |
| 1025 | 17526654 | Using male Sprague-Dawley rats, we performed a time course study [days 7, 14, and 28 after streptozotocin (STZ) injection] to determine changes in phosphorylation of JAK2, STAT1, and STAT3 in thoracic aorta using standard Western blot techniques. |
| 1026 | 17526654 | On day 7 there was no change in phosphorylation of JAK2, STAT1, and STAT3. |
| 1027 | 17526654 | Phosphorylation of JAK2, STAT1, and STAT3 was significantly increased on days 14 and 28 and was inhibited by treatment with candesartan (AT(1) receptor antagonist, 10 mg x kg(-1) x day(-1) orally in drinking water), atrasentan (ET(A) receptor antagonist, 10 mg x kg(-1) x day(-1) orally in drinking water), and AG-490 (JAK2 inhibitor, 5 mg x kg(-1) x day(-1) intraperitoneally). |
| 1028 | 17526654 | Angiotensin II and endothelin-1 augment the vascular complications of diabetes via JAK2 activation. |
| 1029 | 17526654 | The JAK/STAT pathway is activated in vitro by angiotensin II (ANG II) and endothelin-1 (ET-1), which are implicated in the development of diabetic complications. |
| 1030 | 17526654 | We hypothesized that ANG II and ET-1 activate the JAK/STAT pathway in vivo to participate in the development of diabetic vascular complications. |
| 1031 | 17526654 | Using male Sprague-Dawley rats, we performed a time course study [days 7, 14, and 28 after streptozotocin (STZ) injection] to determine changes in phosphorylation of JAK2, STAT1, and STAT3 in thoracic aorta using standard Western blot techniques. |
| 1032 | 17526654 | On day 7 there was no change in phosphorylation of JAK2, STAT1, and STAT3. |
| 1033 | 17526654 | Phosphorylation of JAK2, STAT1, and STAT3 was significantly increased on days 14 and 28 and was inhibited by treatment with candesartan (AT(1) receptor antagonist, 10 mg x kg(-1) x day(-1) orally in drinking water), atrasentan (ET(A) receptor antagonist, 10 mg x kg(-1) x day(-1) orally in drinking water), and AG-490 (JAK2 inhibitor, 5 mg x kg(-1) x day(-1) intraperitoneally). |
| 1034 | 17526654 | Angiotensin II and endothelin-1 augment the vascular complications of diabetes via JAK2 activation. |
| 1035 | 17526654 | The JAK/STAT pathway is activated in vitro by angiotensin II (ANG II) and endothelin-1 (ET-1), which are implicated in the development of diabetic complications. |
| 1036 | 17526654 | We hypothesized that ANG II and ET-1 activate the JAK/STAT pathway in vivo to participate in the development of diabetic vascular complications. |
| 1037 | 17526654 | Using male Sprague-Dawley rats, we performed a time course study [days 7, 14, and 28 after streptozotocin (STZ) injection] to determine changes in phosphorylation of JAK2, STAT1, and STAT3 in thoracic aorta using standard Western blot techniques. |
| 1038 | 17526654 | On day 7 there was no change in phosphorylation of JAK2, STAT1, and STAT3. |
| 1039 | 17526654 | Phosphorylation of JAK2, STAT1, and STAT3 was significantly increased on days 14 and 28 and was inhibited by treatment with candesartan (AT(1) receptor antagonist, 10 mg x kg(-1) x day(-1) orally in drinking water), atrasentan (ET(A) receptor antagonist, 10 mg x kg(-1) x day(-1) orally in drinking water), and AG-490 (JAK2 inhibitor, 5 mg x kg(-1) x day(-1) intraperitoneally). |
| 1040 | 17562326 | The islets from cKO mice demonstrated hyperactivation of STAT3 and higher induction of Bcl-xL than did islets from WT mice, and SOCS3-deficient beta-cells were more resistant to apoptosis induced by STZ in vitro than were WT beta-cells. |
| 1041 | 17562326 | These results suggest that enhanced STAT3 signaling protects beta-cells from destruction induced by a genotoxic stress and that STAT3/SOCS3 can be a potential therapeutic target for the treatment of type 1 diabetes. |
| 1042 | 17562326 | The islets from cKO mice demonstrated hyperactivation of STAT3 and higher induction of Bcl-xL than did islets from WT mice, and SOCS3-deficient beta-cells were more resistant to apoptosis induced by STZ in vitro than were WT beta-cells. |
| 1043 | 17562326 | These results suggest that enhanced STAT3 signaling protects beta-cells from destruction induced by a genotoxic stress and that STAT3/SOCS3 can be a potential therapeutic target for the treatment of type 1 diabetes. |
| 1044 | 17690165 | Indeed, endogenous circulating leptin results in detectable levels of baseline activated signal transducer and activator of transcription 3 (STAT3) phosphorylation in a population of ARC/LRb neurons, consistent with increased sensing of circulating leptin in these neurons compared with other LRb neurons. |
| 1045 | 17690165 | Furthermore, a population of ARC/LRb neurons that responds more rapidly and sensitively to circulating leptin compared with other hypothalamic LRb neurons detected by leptin activated phosphorylated STAT3. |
| 1046 | 17690165 | Indeed, endogenous circulating leptin results in detectable levels of baseline activated signal transducer and activator of transcription 3 (STAT3) phosphorylation in a population of ARC/LRb neurons, consistent with increased sensing of circulating leptin in these neurons compared with other LRb neurons. |
| 1047 | 17690165 | Furthermore, a population of ARC/LRb neurons that responds more rapidly and sensitively to circulating leptin compared with other hypothalamic LRb neurons detected by leptin activated phosphorylated STAT3. |
| 1048 | 18048761 | Among many other possible mechanisms, for example, in hyperlipidemia and diabetes, the pathological increase in reactive oxygen and nitrogen species and the use of the ATP-sensitive potassium channel inhibitor insulin secretagogue antidiabetic drugs and, in aging, the reduced expression of connexin-43 and signal transducer and activator of transcription 3 may disrupt major cytoprotective signaling pathways thereby significantly interfering with the cardioprotective effect of pre- and postconditioning. |
| 1049 | 18077349 | Mutations of HNF-1beta inhibit epithelial morphogenesis through dysregulation of SOCS-3. |
| 1050 | 18077349 | Hepatocyte nuclear factor-1beta (HNF-1beta) is a Pit-1, Oct-1/2, Unc-86 (POU) homeodomain-containing transcription factor expressed in the kidney, liver, pancreas, and other epithelial organs. |
| 1051 | 18077349 | Using genome-wide chromatin immunoprecipitation and DNA microarray (ChIP-chip) and microarray analysis of mRNA expression, we identified SOCS3 (suppressor of cytokine signaling-3) as a previously unrecognized target gene of HNF-1beta in the kidney. |
| 1052 | 18077349 | HNF-1beta binds to the SOCS3 promoter and represses SOCS3 transcription. |
| 1053 | 18077349 | The expression of SOCS3 is increased in HNF-1beta knockout mice and in renal epithelial cells expressing dominant-negative mutant HNF-1beta. |
| 1054 | 18077349 | Increased levels of SOCS-3 inhibit HGF-induced tubulogenesis by decreasing phosphorylation of Erk and STAT-3. |
| 1055 | 18077349 | Conversely, knockdown of SOCS-3 in renal epithelial cells expressing dominant-negative mutant HNF-1beta rescues the defect in HGF-induced tubulogenesis by restoring phosphorylation of Erk and STAT-3. |
| 1056 | 18077349 | Thus, HNF-1beta regulates tubulogenesis by controlling the levels of SOCS-3 expression. |
| 1057 | 18077349 | Manipulating the levels of SOCS-3 may be a useful therapeutic approach for human diseases induced by HNF-1beta mutations. |
| 1058 | 18077349 | Mutations of HNF-1beta inhibit epithelial morphogenesis through dysregulation of SOCS-3. |
| 1059 | 18077349 | Hepatocyte nuclear factor-1beta (HNF-1beta) is a Pit-1, Oct-1/2, Unc-86 (POU) homeodomain-containing transcription factor expressed in the kidney, liver, pancreas, and other epithelial organs. |
| 1060 | 18077349 | Using genome-wide chromatin immunoprecipitation and DNA microarray (ChIP-chip) and microarray analysis of mRNA expression, we identified SOCS3 (suppressor of cytokine signaling-3) as a previously unrecognized target gene of HNF-1beta in the kidney. |
| 1061 | 18077349 | HNF-1beta binds to the SOCS3 promoter and represses SOCS3 transcription. |
| 1062 | 18077349 | The expression of SOCS3 is increased in HNF-1beta knockout mice and in renal epithelial cells expressing dominant-negative mutant HNF-1beta. |
| 1063 | 18077349 | Increased levels of SOCS-3 inhibit HGF-induced tubulogenesis by decreasing phosphorylation of Erk and STAT-3. |
| 1064 | 18077349 | Conversely, knockdown of SOCS-3 in renal epithelial cells expressing dominant-negative mutant HNF-1beta rescues the defect in HGF-induced tubulogenesis by restoring phosphorylation of Erk and STAT-3. |
| 1065 | 18077349 | Thus, HNF-1beta regulates tubulogenesis by controlling the levels of SOCS-3 expression. |
| 1066 | 18077349 | Manipulating the levels of SOCS-3 may be a useful therapeutic approach for human diseases induced by HNF-1beta mutations. |
| 1067 | 18171429 | In order to understand leptin action we have explored the physiological function of LRb signalling pathways, defining important roles for signal transducer and activator of transcription-3 (STAT3) in positive signalling and for LRbTyr(985)-mediated feedback inhibition in leptin signal attenuation. |
| 1068 | 18178618 | On granule exocytosis, the ICA512 cytoplasmic domain is cleaved and the resulting cytosolic fragment (ICA512-CCF) moves into the nucleus where it enhances the levels of phosphorylated STAT5 and STAT3, thereby inducing insulin gene transcription and granule biogenesis. |
| 1069 | 18178618 | We now show that knockdown of ICA512 decreases cyclin D1 levels and proliferation of insulinoma INS-1 cells, whereas beta-cell regeneration is reduced in partially pancreatectomized ICA512-/- mice. |
| 1070 | 18178618 | Up-regulation of cyclin D1 and D2 by ICA512-CCF is affected by knockdown of STAT3 and STAT5, respectively, whereas it does not require insulin signaling. |
| 1071 | 18178618 | On granule exocytosis, the ICA512 cytoplasmic domain is cleaved and the resulting cytosolic fragment (ICA512-CCF) moves into the nucleus where it enhances the levels of phosphorylated STAT5 and STAT3, thereby inducing insulin gene transcription and granule biogenesis. |
| 1072 | 18178618 | We now show that knockdown of ICA512 decreases cyclin D1 levels and proliferation of insulinoma INS-1 cells, whereas beta-cell regeneration is reduced in partially pancreatectomized ICA512-/- mice. |
| 1073 | 18178618 | Up-regulation of cyclin D1 and D2 by ICA512-CCF is affected by knockdown of STAT3 and STAT5, respectively, whereas it does not require insulin signaling. |
| 1074 | 18185532 | SOCS3 negatively regulates the gp130-STAT3 pathway in mouse skin wound healing. |
| 1075 | 18185532 | Proliferation and differentiation of keratinocytes during wound healing are regulated by cytokines and chemokines, which are secreted by resident and inflammatory cells and activate the transcription factor signal transducer and activator of transcription (STAT)3. |
| 1076 | 18185532 | However, it is not clear to what extent STAT3 in keratinocytes is activated by gp130-containing receptors. |
| 1077 | 18185532 | We addressed this question genetically by deleting the suppressor of cytokine signaling (SOCS)3, a negative regulator of gp130-mediated STAT3 activation. |
| 1078 | 18185532 | Deletion of Socs3 using the MMTV-Cre transgene resulted in aberrant STAT3 activation, impaired wound healing, prolonged secretion of chemokines, a hyperproliferative epidermis, and neutrophil infiltration into wounds. |
| 1079 | 18185532 | These results demonstrate that wound healing is controlled in keratinocytes by the gp130-SOCS3-STAT3 pathway and an imbalance of this pathway results in delayed wound healing. |
| 1080 | 18185532 | SOCS3 negatively regulates the gp130-STAT3 pathway in mouse skin wound healing. |
| 1081 | 18185532 | Proliferation and differentiation of keratinocytes during wound healing are regulated by cytokines and chemokines, which are secreted by resident and inflammatory cells and activate the transcription factor signal transducer and activator of transcription (STAT)3. |
| 1082 | 18185532 | However, it is not clear to what extent STAT3 in keratinocytes is activated by gp130-containing receptors. |
| 1083 | 18185532 | We addressed this question genetically by deleting the suppressor of cytokine signaling (SOCS)3, a negative regulator of gp130-mediated STAT3 activation. |
| 1084 | 18185532 | Deletion of Socs3 using the MMTV-Cre transgene resulted in aberrant STAT3 activation, impaired wound healing, prolonged secretion of chemokines, a hyperproliferative epidermis, and neutrophil infiltration into wounds. |
| 1085 | 18185532 | These results demonstrate that wound healing is controlled in keratinocytes by the gp130-SOCS3-STAT3 pathway and an imbalance of this pathway results in delayed wound healing. |
| 1086 | 18185532 | SOCS3 negatively regulates the gp130-STAT3 pathway in mouse skin wound healing. |
| 1087 | 18185532 | Proliferation and differentiation of keratinocytes during wound healing are regulated by cytokines and chemokines, which are secreted by resident and inflammatory cells and activate the transcription factor signal transducer and activator of transcription (STAT)3. |
| 1088 | 18185532 | However, it is not clear to what extent STAT3 in keratinocytes is activated by gp130-containing receptors. |
| 1089 | 18185532 | We addressed this question genetically by deleting the suppressor of cytokine signaling (SOCS)3, a negative regulator of gp130-mediated STAT3 activation. |
| 1090 | 18185532 | Deletion of Socs3 using the MMTV-Cre transgene resulted in aberrant STAT3 activation, impaired wound healing, prolonged secretion of chemokines, a hyperproliferative epidermis, and neutrophil infiltration into wounds. |
| 1091 | 18185532 | These results demonstrate that wound healing is controlled in keratinocytes by the gp130-SOCS3-STAT3 pathway and an imbalance of this pathway results in delayed wound healing. |
| 1092 | 18185532 | SOCS3 negatively regulates the gp130-STAT3 pathway in mouse skin wound healing. |
| 1093 | 18185532 | Proliferation and differentiation of keratinocytes during wound healing are regulated by cytokines and chemokines, which are secreted by resident and inflammatory cells and activate the transcription factor signal transducer and activator of transcription (STAT)3. |
| 1094 | 18185532 | However, it is not clear to what extent STAT3 in keratinocytes is activated by gp130-containing receptors. |
| 1095 | 18185532 | We addressed this question genetically by deleting the suppressor of cytokine signaling (SOCS)3, a negative regulator of gp130-mediated STAT3 activation. |
| 1096 | 18185532 | Deletion of Socs3 using the MMTV-Cre transgene resulted in aberrant STAT3 activation, impaired wound healing, prolonged secretion of chemokines, a hyperproliferative epidermis, and neutrophil infiltration into wounds. |
| 1097 | 18185532 | These results demonstrate that wound healing is controlled in keratinocytes by the gp130-SOCS3-STAT3 pathway and an imbalance of this pathway results in delayed wound healing. |
| 1098 | 18185532 | SOCS3 negatively regulates the gp130-STAT3 pathway in mouse skin wound healing. |
| 1099 | 18185532 | Proliferation and differentiation of keratinocytes during wound healing are regulated by cytokines and chemokines, which are secreted by resident and inflammatory cells and activate the transcription factor signal transducer and activator of transcription (STAT)3. |
| 1100 | 18185532 | However, it is not clear to what extent STAT3 in keratinocytes is activated by gp130-containing receptors. |
| 1101 | 18185532 | We addressed this question genetically by deleting the suppressor of cytokine signaling (SOCS)3, a negative regulator of gp130-mediated STAT3 activation. |
| 1102 | 18185532 | Deletion of Socs3 using the MMTV-Cre transgene resulted in aberrant STAT3 activation, impaired wound healing, prolonged secretion of chemokines, a hyperproliferative epidermis, and neutrophil infiltration into wounds. |
| 1103 | 18185532 | These results demonstrate that wound healing is controlled in keratinocytes by the gp130-SOCS3-STAT3 pathway and an imbalance of this pathway results in delayed wound healing. |
| 1104 | 18185532 | SOCS3 negatively regulates the gp130-STAT3 pathway in mouse skin wound healing. |
| 1105 | 18185532 | Proliferation and differentiation of keratinocytes during wound healing are regulated by cytokines and chemokines, which are secreted by resident and inflammatory cells and activate the transcription factor signal transducer and activator of transcription (STAT)3. |
| 1106 | 18185532 | However, it is not clear to what extent STAT3 in keratinocytes is activated by gp130-containing receptors. |
| 1107 | 18185532 | We addressed this question genetically by deleting the suppressor of cytokine signaling (SOCS)3, a negative regulator of gp130-mediated STAT3 activation. |
| 1108 | 18185532 | Deletion of Socs3 using the MMTV-Cre transgene resulted in aberrant STAT3 activation, impaired wound healing, prolonged secretion of chemokines, a hyperproliferative epidermis, and neutrophil infiltration into wounds. |
| 1109 | 18185532 | These results demonstrate that wound healing is controlled in keratinocytes by the gp130-SOCS3-STAT3 pathway and an imbalance of this pathway results in delayed wound healing. |
| 1110 | 18268048 | STAT3 sensitizes insulin signaling by negatively regulating glycogen synthase kinase-3 beta. |
| 1111 | 18378570 | Role of NADPH oxidase and Stat3 in statin-mediated protection against diabetic retinopathy. |
| 1112 | 18414053 | Resveratrol has also been shown to activate various transcription factor (e.g; NFkappaB, STAT3, HIF-1alpha, beta-catenin and PPAR-gamma), suppress the expression of antiapoptotic gene products (e.g; Bcl-2, Bcl-X(L), XIAP and survivin), inhibit protein kinases (e.g; src, PI3K, JNK, and AKT), induce antioxidant enzymes (e,g; catalase, superoxide dismutase and hemoxygenase-1), suppress the expression of inflammatory biomarkers (e.g., TNF, COX-2, iNOS, and CRP), inhibit the expression of angiogenic and metastatic gene products (e.g., MMPs, VEGF, cathepsin D, and ICAM-1), and modulate cell cycle regulatory genes (e.g., p53, Rb, PTEN, cyclins and CDKs). |
| 1113 | 18437163 | Insulin-like growth factor-I protects cells from ER stress-induced apoptosis via enhancement of the adaptive capacity of endoplasmic reticulum. |
| 1114 | 18437163 | Here we demonstrate that human MCF-7 breast cancer cells, as well as murine NIH/3T3 fibroblasts, are rescued from ER stress-initiated apoptosis by insulin-like growth factor-I (IGF-I). |
| 1115 | 18437163 | IGF-I significantly augments the adaptive capacity of the ER by enhancing compensatory mechanisms such as the IRE1 alpha-, PERK- and ATF6-mediated arms of ER stress signalling. |
| 1116 | 18437163 | During ER stress, IGF-I stimulates translational recovery and induces expression of the key molecular chaperone protein Grp78/BiP, thereby enhancing the folding capacity of the ER and promoting recovery from ER stress. |
| 1117 | 18437163 | Application of signal transduction inhibitors of MEK (U1026), PI3K (LY294002 and wortmannin), JNK (SP600125), p38 (SB203580), protein kinases A and C (H-89 and staurosporine) and STAT3 (Stattic) does not prevent IGF-I-mediated protection from ER stress-induced apoptosis. |
| 1118 | 18451094 | Leukemia inhibitory factor regulates trophoblast giant cell differentiation via Janus kinase 1-signal transducer and activator of transcription 3-suppressor of cytokine signaling 3 pathway. |
| 1119 | 18451094 | Suppressor of cytokine signaling 3 (SOCS3) inhibits leukemia-inhibitory factor (LIF) signaling and acts as a negative regulator. |
| 1120 | 18451094 | Deletion of SOCS3 causes embryonic lethality because of placental failure, and genetic reduction of LIF or the LIF receptor (LIFR) in SOCS3-deficient mice rescues placental defects and embryonic lethality; this indicates that SOCS3 is an essential inhibitor of LIFR signaling. |
| 1121 | 18451094 | However, the downstream signaling molecule that acts as a link between the LIFR and SOCS3 has not been identified. |
| 1122 | 18451094 | The administration of LIF to SOCS3-heterozygous pregnant mice promotes trophoblast giant cell differentiation and accelerates placental failure in SOCS3-deficient mice. |
| 1123 | 18451094 | SOCS3-deficient trophoblast stem cells show enhanced and prolonged signal transducer and activator of transcription 3 (Stat3) activation by LIF stimulation. |
| 1124 | 18451094 | Further, in the trophoblasts of SOCS3-deficient placenta and differentiating cells from the choriocarcinoma-derived cell line Rcho-1 cells, constitutive activation of Stat3 is observed. |
| 1125 | 18451094 | The forced expression of SOCS3, dominant-negative Stat3, and dominant-negative Janus kinase 1 (JAK1) in Rcho-1 cells significantly suppressed the trophoblast giant cell differentiation of these cells. |
| 1126 | 18451094 | Finally, JAK1 deficiency rescues placental defects and embryonic lethality in SOCS3-deficient mice. |
| 1127 | 18451094 | These results indicate that the LIFR signaling is finely coordinated by JAK1, Stat3, and SOCS3 and regulates trophoblast giant cell differentiation. |
| 1128 | 18451094 | In addition, these data establish that LIFR-JAK1-Stat3-SOCS3 signaling is an essential pathway for the regulation of trophoblast giant cell differentiation. |
| 1129 | 18451094 | Leukemia inhibitory factor regulates trophoblast giant cell differentiation via Janus kinase 1-signal transducer and activator of transcription 3-suppressor of cytokine signaling 3 pathway. |
| 1130 | 18451094 | Suppressor of cytokine signaling 3 (SOCS3) inhibits leukemia-inhibitory factor (LIF) signaling and acts as a negative regulator. |
| 1131 | 18451094 | Deletion of SOCS3 causes embryonic lethality because of placental failure, and genetic reduction of LIF or the LIF receptor (LIFR) in SOCS3-deficient mice rescues placental defects and embryonic lethality; this indicates that SOCS3 is an essential inhibitor of LIFR signaling. |
| 1132 | 18451094 | However, the downstream signaling molecule that acts as a link between the LIFR and SOCS3 has not been identified. |
| 1133 | 18451094 | The administration of LIF to SOCS3-heterozygous pregnant mice promotes trophoblast giant cell differentiation and accelerates placental failure in SOCS3-deficient mice. |
| 1134 | 18451094 | SOCS3-deficient trophoblast stem cells show enhanced and prolonged signal transducer and activator of transcription 3 (Stat3) activation by LIF stimulation. |
| 1135 | 18451094 | Further, in the trophoblasts of SOCS3-deficient placenta and differentiating cells from the choriocarcinoma-derived cell line Rcho-1 cells, constitutive activation of Stat3 is observed. |
| 1136 | 18451094 | The forced expression of SOCS3, dominant-negative Stat3, and dominant-negative Janus kinase 1 (JAK1) in Rcho-1 cells significantly suppressed the trophoblast giant cell differentiation of these cells. |
| 1137 | 18451094 | Finally, JAK1 deficiency rescues placental defects and embryonic lethality in SOCS3-deficient mice. |
| 1138 | 18451094 | These results indicate that the LIFR signaling is finely coordinated by JAK1, Stat3, and SOCS3 and regulates trophoblast giant cell differentiation. |
| 1139 | 18451094 | In addition, these data establish that LIFR-JAK1-Stat3-SOCS3 signaling is an essential pathway for the regulation of trophoblast giant cell differentiation. |
| 1140 | 18451094 | Leukemia inhibitory factor regulates trophoblast giant cell differentiation via Janus kinase 1-signal transducer and activator of transcription 3-suppressor of cytokine signaling 3 pathway. |
| 1141 | 18451094 | Suppressor of cytokine signaling 3 (SOCS3) inhibits leukemia-inhibitory factor (LIF) signaling and acts as a negative regulator. |
| 1142 | 18451094 | Deletion of SOCS3 causes embryonic lethality because of placental failure, and genetic reduction of LIF or the LIF receptor (LIFR) in SOCS3-deficient mice rescues placental defects and embryonic lethality; this indicates that SOCS3 is an essential inhibitor of LIFR signaling. |
| 1143 | 18451094 | However, the downstream signaling molecule that acts as a link between the LIFR and SOCS3 has not been identified. |
| 1144 | 18451094 | The administration of LIF to SOCS3-heterozygous pregnant mice promotes trophoblast giant cell differentiation and accelerates placental failure in SOCS3-deficient mice. |
| 1145 | 18451094 | SOCS3-deficient trophoblast stem cells show enhanced and prolonged signal transducer and activator of transcription 3 (Stat3) activation by LIF stimulation. |
| 1146 | 18451094 | Further, in the trophoblasts of SOCS3-deficient placenta and differentiating cells from the choriocarcinoma-derived cell line Rcho-1 cells, constitutive activation of Stat3 is observed. |
| 1147 | 18451094 | The forced expression of SOCS3, dominant-negative Stat3, and dominant-negative Janus kinase 1 (JAK1) in Rcho-1 cells significantly suppressed the trophoblast giant cell differentiation of these cells. |
| 1148 | 18451094 | Finally, JAK1 deficiency rescues placental defects and embryonic lethality in SOCS3-deficient mice. |
| 1149 | 18451094 | These results indicate that the LIFR signaling is finely coordinated by JAK1, Stat3, and SOCS3 and regulates trophoblast giant cell differentiation. |
| 1150 | 18451094 | In addition, these data establish that LIFR-JAK1-Stat3-SOCS3 signaling is an essential pathway for the regulation of trophoblast giant cell differentiation. |
| 1151 | 18451094 | Leukemia inhibitory factor regulates trophoblast giant cell differentiation via Janus kinase 1-signal transducer and activator of transcription 3-suppressor of cytokine signaling 3 pathway. |
| 1152 | 18451094 | Suppressor of cytokine signaling 3 (SOCS3) inhibits leukemia-inhibitory factor (LIF) signaling and acts as a negative regulator. |
| 1153 | 18451094 | Deletion of SOCS3 causes embryonic lethality because of placental failure, and genetic reduction of LIF or the LIF receptor (LIFR) in SOCS3-deficient mice rescues placental defects and embryonic lethality; this indicates that SOCS3 is an essential inhibitor of LIFR signaling. |
| 1154 | 18451094 | However, the downstream signaling molecule that acts as a link between the LIFR and SOCS3 has not been identified. |
| 1155 | 18451094 | The administration of LIF to SOCS3-heterozygous pregnant mice promotes trophoblast giant cell differentiation and accelerates placental failure in SOCS3-deficient mice. |
| 1156 | 18451094 | SOCS3-deficient trophoblast stem cells show enhanced and prolonged signal transducer and activator of transcription 3 (Stat3) activation by LIF stimulation. |
| 1157 | 18451094 | Further, in the trophoblasts of SOCS3-deficient placenta and differentiating cells from the choriocarcinoma-derived cell line Rcho-1 cells, constitutive activation of Stat3 is observed. |
| 1158 | 18451094 | The forced expression of SOCS3, dominant-negative Stat3, and dominant-negative Janus kinase 1 (JAK1) in Rcho-1 cells significantly suppressed the trophoblast giant cell differentiation of these cells. |
| 1159 | 18451094 | Finally, JAK1 deficiency rescues placental defects and embryonic lethality in SOCS3-deficient mice. |
| 1160 | 18451094 | These results indicate that the LIFR signaling is finely coordinated by JAK1, Stat3, and SOCS3 and regulates trophoblast giant cell differentiation. |
| 1161 | 18451094 | In addition, these data establish that LIFR-JAK1-Stat3-SOCS3 signaling is an essential pathway for the regulation of trophoblast giant cell differentiation. |
| 1162 | 18451094 | Leukemia inhibitory factor regulates trophoblast giant cell differentiation via Janus kinase 1-signal transducer and activator of transcription 3-suppressor of cytokine signaling 3 pathway. |
| 1163 | 18451094 | Suppressor of cytokine signaling 3 (SOCS3) inhibits leukemia-inhibitory factor (LIF) signaling and acts as a negative regulator. |
| 1164 | 18451094 | Deletion of SOCS3 causes embryonic lethality because of placental failure, and genetic reduction of LIF or the LIF receptor (LIFR) in SOCS3-deficient mice rescues placental defects and embryonic lethality; this indicates that SOCS3 is an essential inhibitor of LIFR signaling. |
| 1165 | 18451094 | However, the downstream signaling molecule that acts as a link between the LIFR and SOCS3 has not been identified. |
| 1166 | 18451094 | The administration of LIF to SOCS3-heterozygous pregnant mice promotes trophoblast giant cell differentiation and accelerates placental failure in SOCS3-deficient mice. |
| 1167 | 18451094 | SOCS3-deficient trophoblast stem cells show enhanced and prolonged signal transducer and activator of transcription 3 (Stat3) activation by LIF stimulation. |
| 1168 | 18451094 | Further, in the trophoblasts of SOCS3-deficient placenta and differentiating cells from the choriocarcinoma-derived cell line Rcho-1 cells, constitutive activation of Stat3 is observed. |
| 1169 | 18451094 | The forced expression of SOCS3, dominant-negative Stat3, and dominant-negative Janus kinase 1 (JAK1) in Rcho-1 cells significantly suppressed the trophoblast giant cell differentiation of these cells. |
| 1170 | 18451094 | Finally, JAK1 deficiency rescues placental defects and embryonic lethality in SOCS3-deficient mice. |
| 1171 | 18451094 | These results indicate that the LIFR signaling is finely coordinated by JAK1, Stat3, and SOCS3 and regulates trophoblast giant cell differentiation. |
| 1172 | 18451094 | In addition, these data establish that LIFR-JAK1-Stat3-SOCS3 signaling is an essential pathway for the regulation of trophoblast giant cell differentiation. |
| 1173 | 18451094 | Leukemia inhibitory factor regulates trophoblast giant cell differentiation via Janus kinase 1-signal transducer and activator of transcription 3-suppressor of cytokine signaling 3 pathway. |
| 1174 | 18451094 | Suppressor of cytokine signaling 3 (SOCS3) inhibits leukemia-inhibitory factor (LIF) signaling and acts as a negative regulator. |
| 1175 | 18451094 | Deletion of SOCS3 causes embryonic lethality because of placental failure, and genetic reduction of LIF or the LIF receptor (LIFR) in SOCS3-deficient mice rescues placental defects and embryonic lethality; this indicates that SOCS3 is an essential inhibitor of LIFR signaling. |
| 1176 | 18451094 | However, the downstream signaling molecule that acts as a link between the LIFR and SOCS3 has not been identified. |
| 1177 | 18451094 | The administration of LIF to SOCS3-heterozygous pregnant mice promotes trophoblast giant cell differentiation and accelerates placental failure in SOCS3-deficient mice. |
| 1178 | 18451094 | SOCS3-deficient trophoblast stem cells show enhanced and prolonged signal transducer and activator of transcription 3 (Stat3) activation by LIF stimulation. |
| 1179 | 18451094 | Further, in the trophoblasts of SOCS3-deficient placenta and differentiating cells from the choriocarcinoma-derived cell line Rcho-1 cells, constitutive activation of Stat3 is observed. |
| 1180 | 18451094 | The forced expression of SOCS3, dominant-negative Stat3, and dominant-negative Janus kinase 1 (JAK1) in Rcho-1 cells significantly suppressed the trophoblast giant cell differentiation of these cells. |
| 1181 | 18451094 | Finally, JAK1 deficiency rescues placental defects and embryonic lethality in SOCS3-deficient mice. |
| 1182 | 18451094 | These results indicate that the LIFR signaling is finely coordinated by JAK1, Stat3, and SOCS3 and regulates trophoblast giant cell differentiation. |
| 1183 | 18451094 | In addition, these data establish that LIFR-JAK1-Stat3-SOCS3 signaling is an essential pathway for the regulation of trophoblast giant cell differentiation. |
| 1184 | 18451994 | Both strains displayed a dramatic upregulation of hepatic leptin receptor expression, while only IRDeltaper mice displayed increased hepatic Stat3 phosphorylation and Il6 expression. |
| 1185 | 18451994 | Leptin replacement restored hepatic Stat3 phosphorylation and normalized glucose metabolism in these mice, indicating that alterations in glucose metabolism occur largely as a consequence of lipoathrophy upon body-wide IR deletion. |
| 1186 | 18451994 | Moreover, chronic intracerebroventricular insulin treatment of control mice increased fat mass, fat cell size, and adipose tissue lipoprotein lipase expression, indicating that CNS insulin action promotes lipogenesis. |
| 1187 | 18451994 | These studies demonstrate that central insulin action plays an important role in regulating WAT mass and glucose metabolism via hepatic Stat3 activation. |
| 1188 | 18451994 | Both strains displayed a dramatic upregulation of hepatic leptin receptor expression, while only IRDeltaper mice displayed increased hepatic Stat3 phosphorylation and Il6 expression. |
| 1189 | 18451994 | Leptin replacement restored hepatic Stat3 phosphorylation and normalized glucose metabolism in these mice, indicating that alterations in glucose metabolism occur largely as a consequence of lipoathrophy upon body-wide IR deletion. |
| 1190 | 18451994 | Moreover, chronic intracerebroventricular insulin treatment of control mice increased fat mass, fat cell size, and adipose tissue lipoprotein lipase expression, indicating that CNS insulin action promotes lipogenesis. |
| 1191 | 18451994 | These studies demonstrate that central insulin action plays an important role in regulating WAT mass and glucose metabolism via hepatic Stat3 activation. |
| 1192 | 18451994 | Both strains displayed a dramatic upregulation of hepatic leptin receptor expression, while only IRDeltaper mice displayed increased hepatic Stat3 phosphorylation and Il6 expression. |
| 1193 | 18451994 | Leptin replacement restored hepatic Stat3 phosphorylation and normalized glucose metabolism in these mice, indicating that alterations in glucose metabolism occur largely as a consequence of lipoathrophy upon body-wide IR deletion. |
| 1194 | 18451994 | Moreover, chronic intracerebroventricular insulin treatment of control mice increased fat mass, fat cell size, and adipose tissue lipoprotein lipase expression, indicating that CNS insulin action promotes lipogenesis. |
| 1195 | 18451994 | These studies demonstrate that central insulin action plays an important role in regulating WAT mass and glucose metabolism via hepatic Stat3 activation. |
| 1196 | 18460640 | Growth hormone (GH) controls the physiology and pathophysiology of the liver, and its signals are conducted by two members of the family of signal transducers and activators of transcription, STAT5A and STAT5B. |
| 1197 | 18460640 | Mice in which the Stat5a/b locus has been inactivated specifically in hepatocytes display GH resistance, the sex-specific expression of genes associated with liver metabolism and the cytochrome P-450 system is lost, and they develop hepatosteatosis. |
| 1198 | 18460640 | Evidence is accumulating that in the absence of STAT5A/B GH aberrantly activates STAT1 and STAT3 and their downstream target genes and thereby offers a partial explanation of some of the physiological alterations observed in Stat5a/b-null mice and human patients. |
| 1199 | 18460640 | We hypothesize that phenotypic changes observed in the absence of STAT5A/B are due to two distinct molecular consequences: first, the failure of STAT5A/B target genes to be activated by GH and second, the rerouting of GH signaling to other members of the STAT family. |
| 1200 | 18460640 | Rerouting of GH signaling to STAT1 and STAT3 might partially compensate for the loss of STAT5A/B, but it certainly activates biological programs distinct from STAT5A/B. |
| 1201 | 18460640 | Growth hormone (GH) controls the physiology and pathophysiology of the liver, and its signals are conducted by two members of the family of signal transducers and activators of transcription, STAT5A and STAT5B. |
| 1202 | 18460640 | Mice in which the Stat5a/b locus has been inactivated specifically in hepatocytes display GH resistance, the sex-specific expression of genes associated with liver metabolism and the cytochrome P-450 system is lost, and they develop hepatosteatosis. |
| 1203 | 18460640 | Evidence is accumulating that in the absence of STAT5A/B GH aberrantly activates STAT1 and STAT3 and their downstream target genes and thereby offers a partial explanation of some of the physiological alterations observed in Stat5a/b-null mice and human patients. |
| 1204 | 18460640 | We hypothesize that phenotypic changes observed in the absence of STAT5A/B are due to two distinct molecular consequences: first, the failure of STAT5A/B target genes to be activated by GH and second, the rerouting of GH signaling to other members of the STAT family. |
| 1205 | 18460640 | Rerouting of GH signaling to STAT1 and STAT3 might partially compensate for the loss of STAT5A/B, but it certainly activates biological programs distinct from STAT5A/B. |
| 1206 | 18484352 | Data from individual animals were used to identify genes in mouse skeletal muscle whose expression correlated with a known serum marker of skeletal myopathy, creatine kinase activity (CK), after treatment with a peroxisome proliferator-activated receptors (PPAR) agonist, GW610742X. |
| 1207 | 18484352 | Six genes had correlation coefficients of >or=0.90: Mt1a (metallothionein 1a), Rrad (Ras-related associated with diabetes), Ankrd1 (ankyrin repeat domain 1), Stat3 (signal transducer and activator of transcription 3), Socs3 (suppressor of cytokine signalling 3) and Mid1ip1 (Mid1 interacting protein 1). |
| 1208 | 18832793 | We analyzed the changes in neurological severity scores, infarct volume, number of apoptotic neurons, and the expression of G-CSF receptor, phosphorylated signal transducer and activator of transcription 3 (pSTAT3), cellular inhibitor of apoptosis protein 2 (cIAP2), Bcl-2, and Bax in the brain tissue. |
| 1209 | 18832793 | Bax is a pro-apoptotic member of the Bcl-2 protein family. |
| 1210 | 18832793 | The G-CSF also increased the expression of pSTAT3, Bcl-2, and cIAP2 proteins as well as Bcl-2 mRNA, but inhibited Bax protein expression in the brain. |
| 1211 | 18997673 | In vitro, Q223R did not affect leptin signaling as reflected by activation of STAT3. |
| 1212 | 19110536 | In up to 8010 cases and 9733 controls we found some evidence for an association with T1D in the regions containing genes: 2q32/STAT4, 17q21/STAT3, 5p15/ERAP1 (ARTS1), 6q23/TNFAIP3 and 12q13/KIF5A/PIP4K2C with allelic P-values ranging from 3.70 x 10(-3) to 3.20 x 10(-5). |
| 1213 | 19136996 | Leptin binding to LepRb activates the associated Janus kinase-2 (Jak2) tyrosine kinase to promote the phosphorylation of Jak2 and three residues on LepRb; each of these sites mediates a distinct aspect of downstream LepRb signaling, with differing physiologic functions. |
| 1214 | 19136996 | Tyr(1138) --> STAT3 signaling suppresses feeding, but is not required for a number of other leptin actions. |
| 1215 | 19136996 | The role for Tyr(1077), the major regulator of signal transducer and activator of transcription-5 (STAT5) during leptin signaling, in the physiologic response to leptin remains unclear, although the obese phenotype of animals deleted for STAT5 in the brain suggests the potential importance of this signaling pathway. |
| 1216 | 19150989 | Here, we show that BBS proteins are required for leptin receptor (LepR) signaling in the hypothalamus. |
| 1217 | 19150989 | We found that Bbs2(-/-), Bbs4(-/-) and Bbs6(-/-) mice are resistant to the action of leptin to reduce body weight and food intake regardless of serum leptin levels and obesity. |
| 1218 | 19150989 | In addition, activation of hypothalamic STAT3 by leptin is significantly decreased in Bbs2(-/-), Bbs4(-/-) and Bbs6(-/-) mice. |
| 1219 | 19150989 | In contrast, downstream melanocortin receptor signaling is unaffected, indicating that LepR signaling is specifically impaired in Bbs2(-/-), Bbs4(-/-) and Bbs6(-/-) mice. |
| 1220 | 19150989 | Impaired LepR signaling in BBS mice was associated with decreased Pomc gene expression. |
| 1221 | 19150989 | Furthermore, we found that BBS1 protein physically interacts with the LepR and that loss of BBS proteins perturbs LepR trafficking. |
| 1222 | 19150989 | Our data indicate that BBS proteins mediate LepR trafficking and that impaired LepR signaling underlies energy imbalance in BBS. |
| 1223 | 19233843 | Incubating primary hepatocyte cultures with recombinant FGF-19 suppressed the ability of insulin to stimulate fatty acid synthesis. |
| 1224 | 19233843 | FGF-19 also suppressed the insulin-induced expression of sterol regulatory element-binding protein-1c (SREBP-1c), a key transcriptional activator of lipogenic genes. |
| 1225 | 19233843 | FGF-19 inhibition of lipogenic enzyme expression was not mediated by alterations in the activity of the insulin signal transduction pathway or changes in the activity of ERK, p38 MAPK, and AMP-activated protein kinase (AMPK). |
| 1226 | 19233843 | In contrast, FGF-19 increased the activity of STAT3, an inhibitor of SREBP-1c expression and decreased the expression of peroxisome proliferator-activated receptor-gamma coactivator-1beta (PGC-1beta), an activator of SREBP-1c activity. |
| 1227 | 19233843 | FGF-19 also increased the expression of small heterodimer partner (SHP), a transcriptional repressor that inhibits lipogenic enzyme expression via a SREBP-1c-independent mechanism. |
| 1228 | 19233843 | Inhibition of SREBP-1c activity by changes in STAT3 and PGC-1beta activity and inhibition of gene transcription by an elevation in SHP expression can explain the inhibition of lipogenesis caused by FGF-19. |
| 1229 | 19233843 | In summary, the inhibitory effect of FGF-19 on insulin activation of hepatic fatty acid synthesis constitutes a mechanism that would explain the beneficial effect of FGF-19 on metabolic syndrome. |
| 1230 | 19233843 | Incubating primary hepatocyte cultures with recombinant FGF-19 suppressed the ability of insulin to stimulate fatty acid synthesis. |
| 1231 | 19233843 | FGF-19 also suppressed the insulin-induced expression of sterol regulatory element-binding protein-1c (SREBP-1c), a key transcriptional activator of lipogenic genes. |
| 1232 | 19233843 | FGF-19 inhibition of lipogenic enzyme expression was not mediated by alterations in the activity of the insulin signal transduction pathway or changes in the activity of ERK, p38 MAPK, and AMP-activated protein kinase (AMPK). |
| 1233 | 19233843 | In contrast, FGF-19 increased the activity of STAT3, an inhibitor of SREBP-1c expression and decreased the expression of peroxisome proliferator-activated receptor-gamma coactivator-1beta (PGC-1beta), an activator of SREBP-1c activity. |
| 1234 | 19233843 | FGF-19 also increased the expression of small heterodimer partner (SHP), a transcriptional repressor that inhibits lipogenic enzyme expression via a SREBP-1c-independent mechanism. |
| 1235 | 19233843 | Inhibition of SREBP-1c activity by changes in STAT3 and PGC-1beta activity and inhibition of gene transcription by an elevation in SHP expression can explain the inhibition of lipogenesis caused by FGF-19. |
| 1236 | 19233843 | In summary, the inhibitory effect of FGF-19 on insulin activation of hepatic fatty acid synthesis constitutes a mechanism that would explain the beneficial effect of FGF-19 on metabolic syndrome. |
| 1237 | 19258740 | We have now investigated the effects of hepatic overexpression of STAT3, achieved by adenovirus-mediated gene transfer, on glucose and lipid metabolism in insulin-resistant diabetic mice. |
| 1238 | 19258740 | Forced expression of STAT3 reduced blood glucose and plasma insulin concentrations as well as the hepatic abundance of mRNA for phosphoenolpyruvate carboxykinase. |
| 1239 | 19258740 | The hepatic abundance of mRNAs for fatty acid synthase and acetyl-CoA carboxylase, both of which catalyze the synthesis of fatty acids, was increased by overexpression of STAT3, whereas that of mRNAs for sterol regulatory element-binding proteins 1a, 1c, or 2 was unaffected. |
| 1240 | 19258740 | Moreover, the amount of mRNA for acyl-CoA oxidase, which contributes to beta-oxidation, was decreased by forced expression of STAT3. |
| 1241 | 19258740 | These results indicate that forced activation of STAT3 signaling in the liver of insulin-resistant diabetic mice increased the circulating levels of atherogenic lipids through changes in the hepatic expression of genes involved in lipid metabolism. |
| 1242 | 19258740 | We have now investigated the effects of hepatic overexpression of STAT3, achieved by adenovirus-mediated gene transfer, on glucose and lipid metabolism in insulin-resistant diabetic mice. |
| 1243 | 19258740 | Forced expression of STAT3 reduced blood glucose and plasma insulin concentrations as well as the hepatic abundance of mRNA for phosphoenolpyruvate carboxykinase. |
| 1244 | 19258740 | The hepatic abundance of mRNAs for fatty acid synthase and acetyl-CoA carboxylase, both of which catalyze the synthesis of fatty acids, was increased by overexpression of STAT3, whereas that of mRNAs for sterol regulatory element-binding proteins 1a, 1c, or 2 was unaffected. |
| 1245 | 19258740 | Moreover, the amount of mRNA for acyl-CoA oxidase, which contributes to beta-oxidation, was decreased by forced expression of STAT3. |
| 1246 | 19258740 | These results indicate that forced activation of STAT3 signaling in the liver of insulin-resistant diabetic mice increased the circulating levels of atherogenic lipids through changes in the hepatic expression of genes involved in lipid metabolism. |
| 1247 | 19258740 | We have now investigated the effects of hepatic overexpression of STAT3, achieved by adenovirus-mediated gene transfer, on glucose and lipid metabolism in insulin-resistant diabetic mice. |
| 1248 | 19258740 | Forced expression of STAT3 reduced blood glucose and plasma insulin concentrations as well as the hepatic abundance of mRNA for phosphoenolpyruvate carboxykinase. |
| 1249 | 19258740 | The hepatic abundance of mRNAs for fatty acid synthase and acetyl-CoA carboxylase, both of which catalyze the synthesis of fatty acids, was increased by overexpression of STAT3, whereas that of mRNAs for sterol regulatory element-binding proteins 1a, 1c, or 2 was unaffected. |
| 1250 | 19258740 | Moreover, the amount of mRNA for acyl-CoA oxidase, which contributes to beta-oxidation, was decreased by forced expression of STAT3. |
| 1251 | 19258740 | These results indicate that forced activation of STAT3 signaling in the liver of insulin-resistant diabetic mice increased the circulating levels of atherogenic lipids through changes in the hepatic expression of genes involved in lipid metabolism. |
| 1252 | 19258740 | We have now investigated the effects of hepatic overexpression of STAT3, achieved by adenovirus-mediated gene transfer, on glucose and lipid metabolism in insulin-resistant diabetic mice. |
| 1253 | 19258740 | Forced expression of STAT3 reduced blood glucose and plasma insulin concentrations as well as the hepatic abundance of mRNA for phosphoenolpyruvate carboxykinase. |
| 1254 | 19258740 | The hepatic abundance of mRNAs for fatty acid synthase and acetyl-CoA carboxylase, both of which catalyze the synthesis of fatty acids, was increased by overexpression of STAT3, whereas that of mRNAs for sterol regulatory element-binding proteins 1a, 1c, or 2 was unaffected. |
| 1255 | 19258740 | Moreover, the amount of mRNA for acyl-CoA oxidase, which contributes to beta-oxidation, was decreased by forced expression of STAT3. |
| 1256 | 19258740 | These results indicate that forced activation of STAT3 signaling in the liver of insulin-resistant diabetic mice increased the circulating levels of atherogenic lipids through changes in the hepatic expression of genes involved in lipid metabolism. |
| 1257 | 19258740 | We have now investigated the effects of hepatic overexpression of STAT3, achieved by adenovirus-mediated gene transfer, on glucose and lipid metabolism in insulin-resistant diabetic mice. |
| 1258 | 19258740 | Forced expression of STAT3 reduced blood glucose and plasma insulin concentrations as well as the hepatic abundance of mRNA for phosphoenolpyruvate carboxykinase. |
| 1259 | 19258740 | The hepatic abundance of mRNAs for fatty acid synthase and acetyl-CoA carboxylase, both of which catalyze the synthesis of fatty acids, was increased by overexpression of STAT3, whereas that of mRNAs for sterol regulatory element-binding proteins 1a, 1c, or 2 was unaffected. |
| 1260 | 19258740 | Moreover, the amount of mRNA for acyl-CoA oxidase, which contributes to beta-oxidation, was decreased by forced expression of STAT3. |
| 1261 | 19258740 | These results indicate that forced activation of STAT3 signaling in the liver of insulin-resistant diabetic mice increased the circulating levels of atherogenic lipids through changes in the hepatic expression of genes involved in lipid metabolism. |
| 1262 | 19264844 | The regulation of expression of gluconeogenic genes including glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) in the liver plays an important role in glucose homeostasis, because aberrant expression of these genes contributes to the development of type 2 diabetes. |
| 1263 | 19264844 | Herein we demonstrate that phosphorylated STAT3 is required for repression of G6Pase expression by IL-6 in both HepG2 cells and mouse liver. |
| 1264 | 19264844 | Interestingly, PEPCK expression is regulated by STAT3 independent of IL-6 activation. |
| 1265 | 19264844 | Using in vivo chromatin immunoprecipitation, we demonstrate that STAT3 binds to the promoters of the G6Pase, PEPCK, and suppressor of cytokine signaling (SOCS)3 genes, and its recruitment increases at the G6Pase and SOCS3 promoters with IL-6 treatment. |
| 1266 | 19264844 | Whereas persistent recruitment of RNA polymerase II is seen on the SOCS3 promoter, consistent with its induction by IL-6, a decrease in polymerase II recruitment and histone H4 acetylation is seen at the G6Pase promoter with IL-6 treatment. |
| 1267 | 19264844 | The regulation of expression of gluconeogenic genes including glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) in the liver plays an important role in glucose homeostasis, because aberrant expression of these genes contributes to the development of type 2 diabetes. |
| 1268 | 19264844 | Herein we demonstrate that phosphorylated STAT3 is required for repression of G6Pase expression by IL-6 in both HepG2 cells and mouse liver. |
| 1269 | 19264844 | Interestingly, PEPCK expression is regulated by STAT3 independent of IL-6 activation. |
| 1270 | 19264844 | Using in vivo chromatin immunoprecipitation, we demonstrate that STAT3 binds to the promoters of the G6Pase, PEPCK, and suppressor of cytokine signaling (SOCS)3 genes, and its recruitment increases at the G6Pase and SOCS3 promoters with IL-6 treatment. |
| 1271 | 19264844 | Whereas persistent recruitment of RNA polymerase II is seen on the SOCS3 promoter, consistent with its induction by IL-6, a decrease in polymerase II recruitment and histone H4 acetylation is seen at the G6Pase promoter with IL-6 treatment. |
| 1272 | 19264844 | The regulation of expression of gluconeogenic genes including glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) in the liver plays an important role in glucose homeostasis, because aberrant expression of these genes contributes to the development of type 2 diabetes. |
| 1273 | 19264844 | Herein we demonstrate that phosphorylated STAT3 is required for repression of G6Pase expression by IL-6 in both HepG2 cells and mouse liver. |
| 1274 | 19264844 | Interestingly, PEPCK expression is regulated by STAT3 independent of IL-6 activation. |
| 1275 | 19264844 | Using in vivo chromatin immunoprecipitation, we demonstrate that STAT3 binds to the promoters of the G6Pase, PEPCK, and suppressor of cytokine signaling (SOCS)3 genes, and its recruitment increases at the G6Pase and SOCS3 promoters with IL-6 treatment. |
| 1276 | 19264844 | Whereas persistent recruitment of RNA polymerase II is seen on the SOCS3 promoter, consistent with its induction by IL-6, a decrease in polymerase II recruitment and histone H4 acetylation is seen at the G6Pase promoter with IL-6 treatment. |
| 1277 | 19272793 | Ciliary neurotrophic factor (CNTF) signals through STAT3-SOCS3 pathway and protects rat pancreatic islets from cytokine-induced apoptosis. |
| 1278 | 19272793 | The medium contained, when necessary, specific inhibitors of the PI3K, MAPK and JAK/STAT3 pathways. mRNA expression (RT-PCR) and protein phosphorylation (Western blot) of Akt, ERK1/2 and STAT3, and SOCS-3 (RT-PCR and Western blot), as well as glucose-stimulated insulin secretion (GSIS) (Radioimmunoassay), were analyzed. |
| 1279 | 19272793 | Our results showed that Akt, ERK1 and STAT3 mRNA expression, as well as phosphorylated Akt and ERK1/2, was not affected by CNTF treatment. |
| 1280 | 19272793 | CNTF increased cytoplasmatic and nuclear phosphorylated STAT3, and the SOCS3 mRNA and protein expression. |
| 1281 | 19272793 | These effects were blocked by the JAK inhibitor, AG490 and by the STAT3 inhibitor Curcumin, but not by the MAPK inhibitor, PD98059, nor by the PI3K inhibitor, Wortmannin. |
| 1282 | 19272793 | In conclusion, CNTF signals through the JAK2/STAT3 cascade, increases SOCS3 expression, impairs GSIS and protects neonatal pancreatic rat islets from cytokine-induced apoptosis. |
| 1283 | 19272793 | Ciliary neurotrophic factor (CNTF) signals through STAT3-SOCS3 pathway and protects rat pancreatic islets from cytokine-induced apoptosis. |
| 1284 | 19272793 | The medium contained, when necessary, specific inhibitors of the PI3K, MAPK and JAK/STAT3 pathways. mRNA expression (RT-PCR) and protein phosphorylation (Western blot) of Akt, ERK1/2 and STAT3, and SOCS-3 (RT-PCR and Western blot), as well as glucose-stimulated insulin secretion (GSIS) (Radioimmunoassay), were analyzed. |
| 1285 | 19272793 | Our results showed that Akt, ERK1 and STAT3 mRNA expression, as well as phosphorylated Akt and ERK1/2, was not affected by CNTF treatment. |
| 1286 | 19272793 | CNTF increased cytoplasmatic and nuclear phosphorylated STAT3, and the SOCS3 mRNA and protein expression. |
| 1287 | 19272793 | These effects were blocked by the JAK inhibitor, AG490 and by the STAT3 inhibitor Curcumin, but not by the MAPK inhibitor, PD98059, nor by the PI3K inhibitor, Wortmannin. |
| 1288 | 19272793 | In conclusion, CNTF signals through the JAK2/STAT3 cascade, increases SOCS3 expression, impairs GSIS and protects neonatal pancreatic rat islets from cytokine-induced apoptosis. |
| 1289 | 19272793 | Ciliary neurotrophic factor (CNTF) signals through STAT3-SOCS3 pathway and protects rat pancreatic islets from cytokine-induced apoptosis. |
| 1290 | 19272793 | The medium contained, when necessary, specific inhibitors of the PI3K, MAPK and JAK/STAT3 pathways. mRNA expression (RT-PCR) and protein phosphorylation (Western blot) of Akt, ERK1/2 and STAT3, and SOCS-3 (RT-PCR and Western blot), as well as glucose-stimulated insulin secretion (GSIS) (Radioimmunoassay), were analyzed. |
| 1291 | 19272793 | Our results showed that Akt, ERK1 and STAT3 mRNA expression, as well as phosphorylated Akt and ERK1/2, was not affected by CNTF treatment. |
| 1292 | 19272793 | CNTF increased cytoplasmatic and nuclear phosphorylated STAT3, and the SOCS3 mRNA and protein expression. |
| 1293 | 19272793 | These effects were blocked by the JAK inhibitor, AG490 and by the STAT3 inhibitor Curcumin, but not by the MAPK inhibitor, PD98059, nor by the PI3K inhibitor, Wortmannin. |
| 1294 | 19272793 | In conclusion, CNTF signals through the JAK2/STAT3 cascade, increases SOCS3 expression, impairs GSIS and protects neonatal pancreatic rat islets from cytokine-induced apoptosis. |
| 1295 | 19272793 | Ciliary neurotrophic factor (CNTF) signals through STAT3-SOCS3 pathway and protects rat pancreatic islets from cytokine-induced apoptosis. |
| 1296 | 19272793 | The medium contained, when necessary, specific inhibitors of the PI3K, MAPK and JAK/STAT3 pathways. mRNA expression (RT-PCR) and protein phosphorylation (Western blot) of Akt, ERK1/2 and STAT3, and SOCS-3 (RT-PCR and Western blot), as well as glucose-stimulated insulin secretion (GSIS) (Radioimmunoassay), were analyzed. |
| 1297 | 19272793 | Our results showed that Akt, ERK1 and STAT3 mRNA expression, as well as phosphorylated Akt and ERK1/2, was not affected by CNTF treatment. |
| 1298 | 19272793 | CNTF increased cytoplasmatic and nuclear phosphorylated STAT3, and the SOCS3 mRNA and protein expression. |
| 1299 | 19272793 | These effects were blocked by the JAK inhibitor, AG490 and by the STAT3 inhibitor Curcumin, but not by the MAPK inhibitor, PD98059, nor by the PI3K inhibitor, Wortmannin. |
| 1300 | 19272793 | In conclusion, CNTF signals through the JAK2/STAT3 cascade, increases SOCS3 expression, impairs GSIS and protects neonatal pancreatic rat islets from cytokine-induced apoptosis. |
| 1301 | 19272793 | Ciliary neurotrophic factor (CNTF) signals through STAT3-SOCS3 pathway and protects rat pancreatic islets from cytokine-induced apoptosis. |
| 1302 | 19272793 | The medium contained, when necessary, specific inhibitors of the PI3K, MAPK and JAK/STAT3 pathways. mRNA expression (RT-PCR) and protein phosphorylation (Western blot) of Akt, ERK1/2 and STAT3, and SOCS-3 (RT-PCR and Western blot), as well as glucose-stimulated insulin secretion (GSIS) (Radioimmunoassay), were analyzed. |
| 1303 | 19272793 | Our results showed that Akt, ERK1 and STAT3 mRNA expression, as well as phosphorylated Akt and ERK1/2, was not affected by CNTF treatment. |
| 1304 | 19272793 | CNTF increased cytoplasmatic and nuclear phosphorylated STAT3, and the SOCS3 mRNA and protein expression. |
| 1305 | 19272793 | These effects were blocked by the JAK inhibitor, AG490 and by the STAT3 inhibitor Curcumin, but not by the MAPK inhibitor, PD98059, nor by the PI3K inhibitor, Wortmannin. |
| 1306 | 19272793 | In conclusion, CNTF signals through the JAK2/STAT3 cascade, increases SOCS3 expression, impairs GSIS and protects neonatal pancreatic rat islets from cytokine-induced apoptosis. |
| 1307 | 19272793 | Ciliary neurotrophic factor (CNTF) signals through STAT3-SOCS3 pathway and protects rat pancreatic islets from cytokine-induced apoptosis. |
| 1308 | 19272793 | The medium contained, when necessary, specific inhibitors of the PI3K, MAPK and JAK/STAT3 pathways. mRNA expression (RT-PCR) and protein phosphorylation (Western blot) of Akt, ERK1/2 and STAT3, and SOCS-3 (RT-PCR and Western blot), as well as glucose-stimulated insulin secretion (GSIS) (Radioimmunoassay), were analyzed. |
| 1309 | 19272793 | Our results showed that Akt, ERK1 and STAT3 mRNA expression, as well as phosphorylated Akt and ERK1/2, was not affected by CNTF treatment. |
| 1310 | 19272793 | CNTF increased cytoplasmatic and nuclear phosphorylated STAT3, and the SOCS3 mRNA and protein expression. |
| 1311 | 19272793 | These effects were blocked by the JAK inhibitor, AG490 and by the STAT3 inhibitor Curcumin, but not by the MAPK inhibitor, PD98059, nor by the PI3K inhibitor, Wortmannin. |
| 1312 | 19272793 | In conclusion, CNTF signals through the JAK2/STAT3 cascade, increases SOCS3 expression, impairs GSIS and protects neonatal pancreatic rat islets from cytokine-induced apoptosis. |
| 1313 | 19332876 | Loss of STAT5 causes liver fibrosis and cancer development through increased TGF-{beta} and STAT3 activation. |
| 1314 | 19332876 | Transforming growth factor (TGF)-beta levels and STAT3 activity were elevated in liver tissue from STAT5-LKO mice upon CCl(4) treatment. |
| 1315 | 19332876 | To define the molecular link between STAT5 silencing and TGF-beta up-regulation, as well as STAT3 activation, we examined STAT5-null mouse embryonic fibroblasts and primary hepatocytes. |
| 1316 | 19332876 | Protease inhibitor studies revealed that STAT5 deficiency enhanced the stability of mature TGF-beta. |
| 1317 | 19332876 | Immunoprecipitation and immunohistochemistry analyses demonstrated that STAT5, through its N-terminal sequences, could bind to TGF-beta and that retroviral-mediated overexpression of STAT5 decreased TGF-beta levels. |
| 1318 | 19332876 | To confirm the in vivo significance of the N-terminal domain of STAT5, we treated mice that expressed STAT5 lacking the N terminus (STAT5-DeltaN) with CCl(4). |
| 1319 | 19332876 | In conclusion, loss of STAT5 results in elevated TGF-beta levels and enhanced growth hormone-induced STAT3 activity. |
| 1320 | 19332876 | Loss of STAT5 causes liver fibrosis and cancer development through increased TGF-{beta} and STAT3 activation. |
| 1321 | 19332876 | Transforming growth factor (TGF)-beta levels and STAT3 activity were elevated in liver tissue from STAT5-LKO mice upon CCl(4) treatment. |
| 1322 | 19332876 | To define the molecular link between STAT5 silencing and TGF-beta up-regulation, as well as STAT3 activation, we examined STAT5-null mouse embryonic fibroblasts and primary hepatocytes. |
| 1323 | 19332876 | Protease inhibitor studies revealed that STAT5 deficiency enhanced the stability of mature TGF-beta. |
| 1324 | 19332876 | Immunoprecipitation and immunohistochemistry analyses demonstrated that STAT5, through its N-terminal sequences, could bind to TGF-beta and that retroviral-mediated overexpression of STAT5 decreased TGF-beta levels. |
| 1325 | 19332876 | To confirm the in vivo significance of the N-terminal domain of STAT5, we treated mice that expressed STAT5 lacking the N terminus (STAT5-DeltaN) with CCl(4). |
| 1326 | 19332876 | In conclusion, loss of STAT5 results in elevated TGF-beta levels and enhanced growth hormone-induced STAT3 activity. |
| 1327 | 19332876 | Loss of STAT5 causes liver fibrosis and cancer development through increased TGF-{beta} and STAT3 activation. |
| 1328 | 19332876 | Transforming growth factor (TGF)-beta levels and STAT3 activity were elevated in liver tissue from STAT5-LKO mice upon CCl(4) treatment. |
| 1329 | 19332876 | To define the molecular link between STAT5 silencing and TGF-beta up-regulation, as well as STAT3 activation, we examined STAT5-null mouse embryonic fibroblasts and primary hepatocytes. |
| 1330 | 19332876 | Protease inhibitor studies revealed that STAT5 deficiency enhanced the stability of mature TGF-beta. |
| 1331 | 19332876 | Immunoprecipitation and immunohistochemistry analyses demonstrated that STAT5, through its N-terminal sequences, could bind to TGF-beta and that retroviral-mediated overexpression of STAT5 decreased TGF-beta levels. |
| 1332 | 19332876 | To confirm the in vivo significance of the N-terminal domain of STAT5, we treated mice that expressed STAT5 lacking the N terminus (STAT5-DeltaN) with CCl(4). |
| 1333 | 19332876 | In conclusion, loss of STAT5 results in elevated TGF-beta levels and enhanced growth hormone-induced STAT3 activity. |
| 1334 | 19332876 | Loss of STAT5 causes liver fibrosis and cancer development through increased TGF-{beta} and STAT3 activation. |
| 1335 | 19332876 | Transforming growth factor (TGF)-beta levels and STAT3 activity were elevated in liver tissue from STAT5-LKO mice upon CCl(4) treatment. |
| 1336 | 19332876 | To define the molecular link between STAT5 silencing and TGF-beta up-regulation, as well as STAT3 activation, we examined STAT5-null mouse embryonic fibroblasts and primary hepatocytes. |
| 1337 | 19332876 | Protease inhibitor studies revealed that STAT5 deficiency enhanced the stability of mature TGF-beta. |
| 1338 | 19332876 | Immunoprecipitation and immunohistochemistry analyses demonstrated that STAT5, through its N-terminal sequences, could bind to TGF-beta and that retroviral-mediated overexpression of STAT5 decreased TGF-beta levels. |
| 1339 | 19332876 | To confirm the in vivo significance of the N-terminal domain of STAT5, we treated mice that expressed STAT5 lacking the N terminus (STAT5-DeltaN) with CCl(4). |
| 1340 | 19332876 | In conclusion, loss of STAT5 results in elevated TGF-beta levels and enhanced growth hormone-induced STAT3 activity. |
| 1341 | 19375767 | Increased carnitine palmitoyl transferase 1 expression and decreased sterol regulatory element-binding protein 1c expression are associated with reduced intramuscular triglyceride accumulation after insulin therapy in high-fat-diet and streptozotocin-induced diabetic rats. |
| 1342 | 19375767 | Compared with normal rats, untreated diabetic rats had a 30% and 61% increase in lipoprotein lipase protein expression and activity, which were decreased by insulin and gliclazide (P < .05). |
| 1343 | 19375767 | Fatty acid translocase protein was down-regulated by 45% in untreated diabetic rats, which was up-regulated by 31% and 26% with insulin and gliclazide, respectively (P < .05). |
| 1344 | 19375767 | Insulin failed to affect fatty acid transport protein 1 and fatty acid binding protein expressions. |
| 1345 | 19375767 | Moreover, compared with normal rats, untreated diabetic rats had higher expressions of sterol regulatory element-binding protein 1c, tumor necrosis factor alpha, and Tyr(705) phosphorylation of signal transducer and activator of transcription 3 levels, which all were down-regulated after insulin treatment. |
| 1346 | 19390493 | Exposure to uteroplacental insufficiency reduces the expression of signal transducer and activator of transcription 3 and proopiomelanocortin in the hypothalamus of newborn rats. |
| 1347 | 19390493 | Disruption of the signal transducer and activator of transcription 3 (STAT3) in the hypothalamic neurons expressing leptin receptor, results in severe obesity, hyperglycaemia, and hyperinsulinemia. |
| 1348 | 19390493 | Our aim was to investigate the expression of STAT3 and its downstream effector proopiomelanocortin (POMC) in IUGR rats obtained by uterine artery ligation. |
| 1349 | 19390493 | At birth, hypothalamus was dissected and processed to evaluate the expression of STAT3, its phosphorylated form, and POMC. |
| 1350 | 19390493 | STAT3 mRNA, STAT3 protein, phosphorylated STAT3, POMC mRNA, and POMC protein were significantly reduced in IUGR versus sham animals (p < 0.0001, p < 0.05 and p < 0.001, p < 0.01, p < 0.01, respectively). |
| 1351 | 19390493 | Our results suggest that an abnormal intrauterine milieu can affect the hypothalamic expression of STAT3 and POMC at birth, altering the hypothalamic signaling pathways that regulate the energy homeostasis. |
| 1352 | 19390493 | Exposure to uteroplacental insufficiency reduces the expression of signal transducer and activator of transcription 3 and proopiomelanocortin in the hypothalamus of newborn rats. |
| 1353 | 19390493 | Disruption of the signal transducer and activator of transcription 3 (STAT3) in the hypothalamic neurons expressing leptin receptor, results in severe obesity, hyperglycaemia, and hyperinsulinemia. |
| 1354 | 19390493 | Our aim was to investigate the expression of STAT3 and its downstream effector proopiomelanocortin (POMC) in IUGR rats obtained by uterine artery ligation. |
| 1355 | 19390493 | At birth, hypothalamus was dissected and processed to evaluate the expression of STAT3, its phosphorylated form, and POMC. |
| 1356 | 19390493 | STAT3 mRNA, STAT3 protein, phosphorylated STAT3, POMC mRNA, and POMC protein were significantly reduced in IUGR versus sham animals (p < 0.0001, p < 0.05 and p < 0.001, p < 0.01, p < 0.01, respectively). |
| 1357 | 19390493 | Our results suggest that an abnormal intrauterine milieu can affect the hypothalamic expression of STAT3 and POMC at birth, altering the hypothalamic signaling pathways that regulate the energy homeostasis. |
| 1358 | 19390493 | Exposure to uteroplacental insufficiency reduces the expression of signal transducer and activator of transcription 3 and proopiomelanocortin in the hypothalamus of newborn rats. |
| 1359 | 19390493 | Disruption of the signal transducer and activator of transcription 3 (STAT3) in the hypothalamic neurons expressing leptin receptor, results in severe obesity, hyperglycaemia, and hyperinsulinemia. |
| 1360 | 19390493 | Our aim was to investigate the expression of STAT3 and its downstream effector proopiomelanocortin (POMC) in IUGR rats obtained by uterine artery ligation. |
| 1361 | 19390493 | At birth, hypothalamus was dissected and processed to evaluate the expression of STAT3, its phosphorylated form, and POMC. |
| 1362 | 19390493 | STAT3 mRNA, STAT3 protein, phosphorylated STAT3, POMC mRNA, and POMC protein were significantly reduced in IUGR versus sham animals (p < 0.0001, p < 0.05 and p < 0.001, p < 0.01, p < 0.01, respectively). |
| 1363 | 19390493 | Our results suggest that an abnormal intrauterine milieu can affect the hypothalamic expression of STAT3 and POMC at birth, altering the hypothalamic signaling pathways that regulate the energy homeostasis. |
| 1364 | 19390493 | Exposure to uteroplacental insufficiency reduces the expression of signal transducer and activator of transcription 3 and proopiomelanocortin in the hypothalamus of newborn rats. |
| 1365 | 19390493 | Disruption of the signal transducer and activator of transcription 3 (STAT3) in the hypothalamic neurons expressing leptin receptor, results in severe obesity, hyperglycaemia, and hyperinsulinemia. |
| 1366 | 19390493 | Our aim was to investigate the expression of STAT3 and its downstream effector proopiomelanocortin (POMC) in IUGR rats obtained by uterine artery ligation. |
| 1367 | 19390493 | At birth, hypothalamus was dissected and processed to evaluate the expression of STAT3, its phosphorylated form, and POMC. |
| 1368 | 19390493 | STAT3 mRNA, STAT3 protein, phosphorylated STAT3, POMC mRNA, and POMC protein were significantly reduced in IUGR versus sham animals (p < 0.0001, p < 0.05 and p < 0.001, p < 0.01, p < 0.01, respectively). |
| 1369 | 19390493 | Our results suggest that an abnormal intrauterine milieu can affect the hypothalamic expression of STAT3 and POMC at birth, altering the hypothalamic signaling pathways that regulate the energy homeostasis. |
| 1370 | 19390493 | Exposure to uteroplacental insufficiency reduces the expression of signal transducer and activator of transcription 3 and proopiomelanocortin in the hypothalamus of newborn rats. |
| 1371 | 19390493 | Disruption of the signal transducer and activator of transcription 3 (STAT3) in the hypothalamic neurons expressing leptin receptor, results in severe obesity, hyperglycaemia, and hyperinsulinemia. |
| 1372 | 19390493 | Our aim was to investigate the expression of STAT3 and its downstream effector proopiomelanocortin (POMC) in IUGR rats obtained by uterine artery ligation. |
| 1373 | 19390493 | At birth, hypothalamus was dissected and processed to evaluate the expression of STAT3, its phosphorylated form, and POMC. |
| 1374 | 19390493 | STAT3 mRNA, STAT3 protein, phosphorylated STAT3, POMC mRNA, and POMC protein were significantly reduced in IUGR versus sham animals (p < 0.0001, p < 0.05 and p < 0.001, p < 0.01, p < 0.01, respectively). |
| 1375 | 19390493 | Our results suggest that an abnormal intrauterine milieu can affect the hypothalamic expression of STAT3 and POMC at birth, altering the hypothalamic signaling pathways that regulate the energy homeostasis. |
| 1376 | 19390493 | Exposure to uteroplacental insufficiency reduces the expression of signal transducer and activator of transcription 3 and proopiomelanocortin in the hypothalamus of newborn rats. |
| 1377 | 19390493 | Disruption of the signal transducer and activator of transcription 3 (STAT3) in the hypothalamic neurons expressing leptin receptor, results in severe obesity, hyperglycaemia, and hyperinsulinemia. |
| 1378 | 19390493 | Our aim was to investigate the expression of STAT3 and its downstream effector proopiomelanocortin (POMC) in IUGR rats obtained by uterine artery ligation. |
| 1379 | 19390493 | At birth, hypothalamus was dissected and processed to evaluate the expression of STAT3, its phosphorylated form, and POMC. |
| 1380 | 19390493 | STAT3 mRNA, STAT3 protein, phosphorylated STAT3, POMC mRNA, and POMC protein were significantly reduced in IUGR versus sham animals (p < 0.0001, p < 0.05 and p < 0.001, p < 0.01, p < 0.01, respectively). |
| 1381 | 19390493 | Our results suggest that an abnormal intrauterine milieu can affect the hypothalamic expression of STAT3 and POMC at birth, altering the hypothalamic signaling pathways that regulate the energy homeostasis. |
| 1382 | 19547759 | Diminished expression of ICOS, GITR and CTLA-4 at the mRNA level in T regulatory cells of children with newly diagnosed type 1 diabetes. |
| 1383 | 19547759 | The percentages of CD4(+)CD25(high)CD127(dim/-) were very low and did not differ between T1DM and control children. |
| 1384 | 19547759 | We did not observe any statistically significant differences between healthy and diabetic children in mRNA expression for FoxP3, IL-7R (CD127), IL-8RA, IL-10RA, IL-12A, IL-2RA (CD25), IL-21, STAT1, STAT3, SOCS2, SOCS3, TGF-beta1-R1, TGF-beta-R2 and TBX-21 genes. |
| 1385 | 19547759 | Interestingly the mRNA level for CTLA-4, ICOS1, IL-23, IL-27, SMAD3 and GITR were lower in Treg cells of children with diabetes compared to the control patients. |
| 1386 | 19549853 | SirT1 knockdown in liver decreases basal hepatic glucose production and increases hepatic insulin responsiveness in diabetic rats. |
| 1387 | 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. |
| 1388 | 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. |
| 1389 | 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. |
| 1390 | 19661066 | Berberine differentially modulates the activities of ERK, p38 MAPK, and JNK to suppress Th17 and Th1 T cell differentiation in type 1 diabetic mice. |
| 1391 | 19661066 | We found that berberine inhibited Th17 differentiation by activating ERK1/2 and inhibited Th1 differentiation by inhibiting p38 MAPK and JNK activation. |
| 1392 | 19661066 | Berberine down-regulated the activity of STAT1 and STAT4 through the suppression of p38 MAPK and JNK activation, and it controlled the stability of STAT4 through the ubiquitin-proteasome pathway. |
| 1393 | 19661066 | This study revealed a novel role of ERK in Th17 differentiation through down-regulation of STAT3 phosphorylation and RORgamma t expression. |
| 1394 | 19696171 | Inhibition of JAK2/STAT3-mediated VEGF upregulation under high glucose conditions by PEDF through a mitochondrial ROS pathway in vitro. |
| 1395 | 19786623 | Oral administration of TC-7020 reduced weight gain and food intake, reduced elevated glucose and glycated hemoglobin levels, and lowered elevated plasma levels of triglycerides and the proinflammatory cytokine tumor necrosis factor-alpha. |
| 1396 | 19786623 | Prevention of weight gain, decreased food intake, and normalization of glucose levels were also blocked by the Janus kinase 2 (JAK2) inhibitor alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide (AG-490), suggesting that these effects involve linkage of alpha7 nAChRs to the JAK2-signal transducer and activator of transcription 3 signaling pathway. |
| 1397 | 19800083 | Humanin induced signal transducer and activator of transcription 3 and extracellular signal-regulated kinase phosphorylation over a 24-hour time course. |
| 1398 | 19875458 | Signal transducer and activator of transcription 3 (STAT3) mediates amino acid inhibition of insulin signaling through serine 727 phosphorylation. |
| 1399 | 19875458 | Here, we report that STAT3 plays a key role in amino acid dampening of insulin signaling in hepatic cells. |
| 1400 | 19875458 | Excess amino acids inhibited insulin-stimulated Akt phosphorylation and glycogen synthesis in mouse primary hepatocytes as well as in human hepatocarcinoma HepG2 cells. |
| 1401 | 19875458 | STAT3 knockdown protected insulin sensitivity from inhibition by amino acids. |
| 1402 | 19875458 | Replacement of the endogenous STAT3 with wild-type, but not S727A, recombinant STAT3 restored the ability of amino acids to inhibit insulin signaling, suggesting that Ser(727) phosphorylation was critical for STAT3-mediated amino acid effect. |
| 1403 | 19875458 | Furthermore, overexpression of STAT3-S727D was sufficient to inhibit insulin signaling in the absence of excess amino acids. |
| 1404 | 19875458 | Finally, we found that STAT3 activity and the expression of its target gene socs3, known to be involved in insulin resistance, were both stimulated by excess amino acids and inhibited by rapamycin. |
| 1405 | 19875458 | In conclusion, our study reveals STAT3 as a novel mediator of nutrient signals and identifies a Ser(727) phosphorylation-dependent and Tyr(705) phosphorylation-independent STAT3 activation mechanism in the modulation of insulin signaling. |
| 1406 | 19875458 | Signal transducer and activator of transcription 3 (STAT3) mediates amino acid inhibition of insulin signaling through serine 727 phosphorylation. |
| 1407 | 19875458 | Here, we report that STAT3 plays a key role in amino acid dampening of insulin signaling in hepatic cells. |
| 1408 | 19875458 | Excess amino acids inhibited insulin-stimulated Akt phosphorylation and glycogen synthesis in mouse primary hepatocytes as well as in human hepatocarcinoma HepG2 cells. |
| 1409 | 19875458 | STAT3 knockdown protected insulin sensitivity from inhibition by amino acids. |
| 1410 | 19875458 | Replacement of the endogenous STAT3 with wild-type, but not S727A, recombinant STAT3 restored the ability of amino acids to inhibit insulin signaling, suggesting that Ser(727) phosphorylation was critical for STAT3-mediated amino acid effect. |
| 1411 | 19875458 | Furthermore, overexpression of STAT3-S727D was sufficient to inhibit insulin signaling in the absence of excess amino acids. |
| 1412 | 19875458 | Finally, we found that STAT3 activity and the expression of its target gene socs3, known to be involved in insulin resistance, were both stimulated by excess amino acids and inhibited by rapamycin. |
| 1413 | 19875458 | In conclusion, our study reveals STAT3 as a novel mediator of nutrient signals and identifies a Ser(727) phosphorylation-dependent and Tyr(705) phosphorylation-independent STAT3 activation mechanism in the modulation of insulin signaling. |
| 1414 | 19875458 | Signal transducer and activator of transcription 3 (STAT3) mediates amino acid inhibition of insulin signaling through serine 727 phosphorylation. |
| 1415 | 19875458 | Here, we report that STAT3 plays a key role in amino acid dampening of insulin signaling in hepatic cells. |
| 1416 | 19875458 | Excess amino acids inhibited insulin-stimulated Akt phosphorylation and glycogen synthesis in mouse primary hepatocytes as well as in human hepatocarcinoma HepG2 cells. |
| 1417 | 19875458 | STAT3 knockdown protected insulin sensitivity from inhibition by amino acids. |
| 1418 | 19875458 | Replacement of the endogenous STAT3 with wild-type, but not S727A, recombinant STAT3 restored the ability of amino acids to inhibit insulin signaling, suggesting that Ser(727) phosphorylation was critical for STAT3-mediated amino acid effect. |
| 1419 | 19875458 | Furthermore, overexpression of STAT3-S727D was sufficient to inhibit insulin signaling in the absence of excess amino acids. |
| 1420 | 19875458 | Finally, we found that STAT3 activity and the expression of its target gene socs3, known to be involved in insulin resistance, were both stimulated by excess amino acids and inhibited by rapamycin. |
| 1421 | 19875458 | In conclusion, our study reveals STAT3 as a novel mediator of nutrient signals and identifies a Ser(727) phosphorylation-dependent and Tyr(705) phosphorylation-independent STAT3 activation mechanism in the modulation of insulin signaling. |
| 1422 | 19875458 | Signal transducer and activator of transcription 3 (STAT3) mediates amino acid inhibition of insulin signaling through serine 727 phosphorylation. |
| 1423 | 19875458 | Here, we report that STAT3 plays a key role in amino acid dampening of insulin signaling in hepatic cells. |
| 1424 | 19875458 | Excess amino acids inhibited insulin-stimulated Akt phosphorylation and glycogen synthesis in mouse primary hepatocytes as well as in human hepatocarcinoma HepG2 cells. |
| 1425 | 19875458 | STAT3 knockdown protected insulin sensitivity from inhibition by amino acids. |
| 1426 | 19875458 | Replacement of the endogenous STAT3 with wild-type, but not S727A, recombinant STAT3 restored the ability of amino acids to inhibit insulin signaling, suggesting that Ser(727) phosphorylation was critical for STAT3-mediated amino acid effect. |
| 1427 | 19875458 | Furthermore, overexpression of STAT3-S727D was sufficient to inhibit insulin signaling in the absence of excess amino acids. |
| 1428 | 19875458 | Finally, we found that STAT3 activity and the expression of its target gene socs3, known to be involved in insulin resistance, were both stimulated by excess amino acids and inhibited by rapamycin. |
| 1429 | 19875458 | In conclusion, our study reveals STAT3 as a novel mediator of nutrient signals and identifies a Ser(727) phosphorylation-dependent and Tyr(705) phosphorylation-independent STAT3 activation mechanism in the modulation of insulin signaling. |
| 1430 | 19875458 | Signal transducer and activator of transcription 3 (STAT3) mediates amino acid inhibition of insulin signaling through serine 727 phosphorylation. |
| 1431 | 19875458 | Here, we report that STAT3 plays a key role in amino acid dampening of insulin signaling in hepatic cells. |
| 1432 | 19875458 | Excess amino acids inhibited insulin-stimulated Akt phosphorylation and glycogen synthesis in mouse primary hepatocytes as well as in human hepatocarcinoma HepG2 cells. |
| 1433 | 19875458 | STAT3 knockdown protected insulin sensitivity from inhibition by amino acids. |
| 1434 | 19875458 | Replacement of the endogenous STAT3 with wild-type, but not S727A, recombinant STAT3 restored the ability of amino acids to inhibit insulin signaling, suggesting that Ser(727) phosphorylation was critical for STAT3-mediated amino acid effect. |
| 1435 | 19875458 | Furthermore, overexpression of STAT3-S727D was sufficient to inhibit insulin signaling in the absence of excess amino acids. |
| 1436 | 19875458 | Finally, we found that STAT3 activity and the expression of its target gene socs3, known to be involved in insulin resistance, were both stimulated by excess amino acids and inhibited by rapamycin. |
| 1437 | 19875458 | In conclusion, our study reveals STAT3 as a novel mediator of nutrient signals and identifies a Ser(727) phosphorylation-dependent and Tyr(705) phosphorylation-independent STAT3 activation mechanism in the modulation of insulin signaling. |
| 1438 | 19875458 | Signal transducer and activator of transcription 3 (STAT3) mediates amino acid inhibition of insulin signaling through serine 727 phosphorylation. |
| 1439 | 19875458 | Here, we report that STAT3 plays a key role in amino acid dampening of insulin signaling in hepatic cells. |
| 1440 | 19875458 | Excess amino acids inhibited insulin-stimulated Akt phosphorylation and glycogen synthesis in mouse primary hepatocytes as well as in human hepatocarcinoma HepG2 cells. |
| 1441 | 19875458 | STAT3 knockdown protected insulin sensitivity from inhibition by amino acids. |
| 1442 | 19875458 | Replacement of the endogenous STAT3 with wild-type, but not S727A, recombinant STAT3 restored the ability of amino acids to inhibit insulin signaling, suggesting that Ser(727) phosphorylation was critical for STAT3-mediated amino acid effect. |
| 1443 | 19875458 | Furthermore, overexpression of STAT3-S727D was sufficient to inhibit insulin signaling in the absence of excess amino acids. |
| 1444 | 19875458 | Finally, we found that STAT3 activity and the expression of its target gene socs3, known to be involved in insulin resistance, were both stimulated by excess amino acids and inhibited by rapamycin. |
| 1445 | 19875458 | In conclusion, our study reveals STAT3 as a novel mediator of nutrient signals and identifies a Ser(727) phosphorylation-dependent and Tyr(705) phosphorylation-independent STAT3 activation mechanism in the modulation of insulin signaling. |
| 1446 | 19875458 | Signal transducer and activator of transcription 3 (STAT3) mediates amino acid inhibition of insulin signaling through serine 727 phosphorylation. |
| 1447 | 19875458 | Here, we report that STAT3 plays a key role in amino acid dampening of insulin signaling in hepatic cells. |
| 1448 | 19875458 | Excess amino acids inhibited insulin-stimulated Akt phosphorylation and glycogen synthesis in mouse primary hepatocytes as well as in human hepatocarcinoma HepG2 cells. |
| 1449 | 19875458 | STAT3 knockdown protected insulin sensitivity from inhibition by amino acids. |
| 1450 | 19875458 | Replacement of the endogenous STAT3 with wild-type, but not S727A, recombinant STAT3 restored the ability of amino acids to inhibit insulin signaling, suggesting that Ser(727) phosphorylation was critical for STAT3-mediated amino acid effect. |
| 1451 | 19875458 | Furthermore, overexpression of STAT3-S727D was sufficient to inhibit insulin signaling in the absence of excess amino acids. |
| 1452 | 19875458 | Finally, we found that STAT3 activity and the expression of its target gene socs3, known to be involved in insulin resistance, were both stimulated by excess amino acids and inhibited by rapamycin. |
| 1453 | 19875458 | In conclusion, our study reveals STAT3 as a novel mediator of nutrient signals and identifies a Ser(727) phosphorylation-dependent and Tyr(705) phosphorylation-independent STAT3 activation mechanism in the modulation of insulin signaling. |
| 1454 | 19911006 | AATF mediates an antiapoptotic effect of the unfolded protein response through transcriptional regulation of AKT1. |
| 1455 | 19911006 | Through the gene expression profiling of beta-cells lacking Wolfram syndrome 1 gene (WFS1), a causative gene for Wolfram syndrome, we discovered a novel antiapoptotic gene of the unfolded protein response (UPR), apoptosis antagonizing transcription factor (AATF). |
| 1456 | 19911006 | We show that AATF is induced by ER stress through the PERK-eIF2alpha pathway and transcriptionally activates the v-akt murine thymoma viral oncogene homolog 1 (AKT1) gene through signal transducer and activator of transcription 3 (Stat3), which sustains Akt1 activation and promotes cell survival. |
| 1457 | 19911006 | Ectopic expression of AATF or a constitutively active form of AKT1 confers on cells resistance to ER stress-mediated cell death, whereas RNAi-mediated knockdown of AATF or AKT1 renders cells sensitive to ER stress. |
| 1458 | 19911006 | We also discovered a positive crosstalk between the AATF and WFS1 signaling pathways. |
| 1459 | 19911006 | Thus, WFS1 deficiency or AATF deficiency mediates a self-perpetuating cycle of cell death. |
| 1460 | 19924142 | The suppressor of cytokine signaling (SOCS)-3 determines keratinocyte proliferative and migratory potential during skin repair. |
| 1461 | 19924142 | Recently, the suppressor of cytokine signaling (SOCS)-3 has been shown to be expressed in disturbed wound margin epithelia during diabetes-impaired wound healing in mice. |
| 1462 | 19924142 | To functionally connect a potential contribution of SOCS-3 expression to the control of wound keratinocyte behavior in skin repair, we created a transgenic mouse (tsgn-K5/SOCS3) overexpressing SOCS-3 in keratinocytes using the bovine keratin 5 promoter. |
| 1463 | 19924142 | Keratinocytes of tsgn-K5/SOCS3 mice showed full inhibition of signal transducer and activator of transcription (STAT)-3 phosphorylation. |
| 1464 | 19924142 | In addition, tsgn-K5/SOCS3 keratinocytes co-expressed the differentiation marker loricrin in the basal layer of nonwounded skin in vivo. |
| 1465 | 20375183 | Mammalian Sirt1 is the most closely related homolog of the SIR2 gene. |
| 1466 | 20375183 | Insulin and leptin signaling regulate food intake by controlling the expression of orexigenic and anorexigenic neuropeptides in the arcuate nucleus of the hypothalamus via Forkhead box O (Foxo)-1 and signal transducer and activator of transcription-3. |
| 1467 | 20375183 | Sirt1 has been reported to improve insulin sensitivity in vitro, but the role of hypothalamic Sirt1 in regulating feeding has not been addressed. |
| 1468 | 20375183 | Forced expression of wild-type Sirt1 in the mediobasal hypothalamus by adenovirus microinjection suppressed Foxo1-induced hyperphagia, a model for central insulin resistance. |
| 1469 | 20484139 | T-cell protein tyrosine phosphatase attenuates STAT3 and insulin signaling in the liver to regulate gluconeogenesis. |
| 1470 | 20488947 | UPR-mediated TRIB3 expression correlates with reduced AKT phosphorylation and inability of interleukin 6 to overcome palmitate-induced apoptosis in RINm5F cells. |
| 1471 | 20488947 | In the present study, we have demonstrated that PA selectively disrupts IL6-induced RAC-alpha serine/threonine-protein kinase (AKT) activation without interfering with signal transducer and activator of transcription 3 phosphorylation in RINm5F cells. |
| 1472 | 20488947 | The inability of IL6 to activate AKT in the presence of PA correlated with an inefficient protection against PA-induced apoptosis. |
| 1473 | 20488947 | In addition, we have demonstrated that IL6 is unable to overcome PA-stimulated UPR, as assessed by activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP) expression, X-box binding protein-1 gene mRNA splicing, and pancreatic eukaryotic initiation factor-2 alpha kinase phosphorylation, whereas no significant induction of UPR by pro-inflammatory cytokines was detected. |
| 1474 | 20488947 | This unconditional stimulation of UPR and apoptosis by PA was accompanied by the stimulation of CHOP and tribble3 (TRIB3) expression, irrespective of the presence of IL6. |
| 1475 | 20488947 | In this way, CHOP and ATF4 might mediate PA-induced TRIB3 expression and, by extension, the suppression of IL6 activation of pro-survival kinase AKT. |
| 1476 | 20818497 | Further studies identified that UA treatment suppressed diabetes-induced activations of STAT-3, ERK1/2 and JNK pathways, but not the diabetes-induced activation of the p38 pathway. |
| 1477 | 20823453 | Skeletal muscle signaling increased after 1 h of rhIL-6 infusion, indicated by a fourfold increase in the phosphorylated signal transducer and activator of transcription (STAT) 3-to-STAT3 ratio, whereas no changes in phosphorylated AMP-activated protein kinase or acetyl-CoA carboxylase levels could be observed. |
| 1478 | 20846165 | Adipocytes are now recognized as an important source of cytokine and chemokine production, including interleukin (IL)-6 and monocyte chemotractant protein (MCP)-1, and this appears to be a key step in the development of the obesity-associated inflammatory state. |
| 1479 | 20846165 | IL-10 was ineffective against TLR-4-induced cytokine secretion due to lack of IL-10 receptor on human adipocytes, in contrast to the widely used murine 3T3-L1 adipocyte model, which is known to respond to IL-10. |
| 1480 | 20846165 | Adenoviral delivery of an IL-10 receptor construct to the cells restored IL-10 responsiveness as assessed by signal transducer and activator of transcription-3 (STAT-3) phosphorylation. |
| 1481 | 20846165 | However, the small molecule nuclear factor (NF)-κB inhibitors 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA)-1 and carbobenzoxyl-Ile-Glu(O-t-butyl)-Ala-leucinal (PSI) as well as adenovirally delivered dominant negative inhibitor of IkappaB kinase 2 (IKK2) and wild-type IκBα were effective inhibitors of TLR-4-driven IL-6 and MCP-1 induction. |
| 1482 | 20978825 | Adiponectin reduces C-reactive protein expression and downregulates STAT3 phosphorylation induced by IL-6 in HepG2 cells. |
| 1483 | 20978825 | CRP is predominately synthesized by hepatocytes when stimulated by interleukin-6 (IL-6). |
| 1484 | 20978825 | In response to IL-6, the signal transducer and activator of transcription 3 (STAT3) becomes phosphorylated on tyrosine and serine residues. |
| 1485 | 20978825 | Phosphorylated STAT3 then activates CRP gene transcription. |
| 1486 | 20978825 | In obesity-related disorders such as diabetes, metabolic syndrome, and cardiovascular diseases, the circulating levels of CRP and adiponectin are inversely correlated, suggesting that these two factors might reciprocally regulate each other. |
| 1487 | 20978825 | We investigated the possibility that adiponectin inhibits CRP production in HepG(2) cells elicited by IL-6. |
| 1488 | 20978825 | CRP gene expression was determined using ELISA and semi-quantitative RT-PCR, and the phosphorylation of STAT3 was investigated with western blot. |
| 1489 | 20978825 | Adiponectin reduced IL-6-induced CRP mRNA levels in HepG(2) cells and CRP protein secretion. |
| 1490 | 20978825 | Preincubating HepG(2) cells with adiponectin led to a decline in STAT3 phosphorylation on both tyrosine and serine residues. |
| 1491 | 20978825 | Our results demonstrated that adiponectin suppresses CRP synthesis and secretion from HepG(2) cells and suggested that the suppression may be mediated through inhibition of the STAT3 pathway. |
| 1492 | 20978825 | Adiponectin reduces C-reactive protein expression and downregulates STAT3 phosphorylation induced by IL-6 in HepG2 cells. |
| 1493 | 20978825 | CRP is predominately synthesized by hepatocytes when stimulated by interleukin-6 (IL-6). |
| 1494 | 20978825 | In response to IL-6, the signal transducer and activator of transcription 3 (STAT3) becomes phosphorylated on tyrosine and serine residues. |
| 1495 | 20978825 | Phosphorylated STAT3 then activates CRP gene transcription. |
| 1496 | 20978825 | In obesity-related disorders such as diabetes, metabolic syndrome, and cardiovascular diseases, the circulating levels of CRP and adiponectin are inversely correlated, suggesting that these two factors might reciprocally regulate each other. |
| 1497 | 20978825 | We investigated the possibility that adiponectin inhibits CRP production in HepG(2) cells elicited by IL-6. |
| 1498 | 20978825 | CRP gene expression was determined using ELISA and semi-quantitative RT-PCR, and the phosphorylation of STAT3 was investigated with western blot. |
| 1499 | 20978825 | Adiponectin reduced IL-6-induced CRP mRNA levels in HepG(2) cells and CRP protein secretion. |
| 1500 | 20978825 | Preincubating HepG(2) cells with adiponectin led to a decline in STAT3 phosphorylation on both tyrosine and serine residues. |
| 1501 | 20978825 | Our results demonstrated that adiponectin suppresses CRP synthesis and secretion from HepG(2) cells and suggested that the suppression may be mediated through inhibition of the STAT3 pathway. |
| 1502 | 20978825 | Adiponectin reduces C-reactive protein expression and downregulates STAT3 phosphorylation induced by IL-6 in HepG2 cells. |
| 1503 | 20978825 | CRP is predominately synthesized by hepatocytes when stimulated by interleukin-6 (IL-6). |
| 1504 | 20978825 | In response to IL-6, the signal transducer and activator of transcription 3 (STAT3) becomes phosphorylated on tyrosine and serine residues. |
| 1505 | 20978825 | Phosphorylated STAT3 then activates CRP gene transcription. |
| 1506 | 20978825 | In obesity-related disorders such as diabetes, metabolic syndrome, and cardiovascular diseases, the circulating levels of CRP and adiponectin are inversely correlated, suggesting that these two factors might reciprocally regulate each other. |
| 1507 | 20978825 | We investigated the possibility that adiponectin inhibits CRP production in HepG(2) cells elicited by IL-6. |
| 1508 | 20978825 | CRP gene expression was determined using ELISA and semi-quantitative RT-PCR, and the phosphorylation of STAT3 was investigated with western blot. |
| 1509 | 20978825 | Adiponectin reduced IL-6-induced CRP mRNA levels in HepG(2) cells and CRP protein secretion. |
| 1510 | 20978825 | Preincubating HepG(2) cells with adiponectin led to a decline in STAT3 phosphorylation on both tyrosine and serine residues. |
| 1511 | 20978825 | Our results demonstrated that adiponectin suppresses CRP synthesis and secretion from HepG(2) cells and suggested that the suppression may be mediated through inhibition of the STAT3 pathway. |
| 1512 | 20978825 | Adiponectin reduces C-reactive protein expression and downregulates STAT3 phosphorylation induced by IL-6 in HepG2 cells. |
| 1513 | 20978825 | CRP is predominately synthesized by hepatocytes when stimulated by interleukin-6 (IL-6). |
| 1514 | 20978825 | In response to IL-6, the signal transducer and activator of transcription 3 (STAT3) becomes phosphorylated on tyrosine and serine residues. |
| 1515 | 20978825 | Phosphorylated STAT3 then activates CRP gene transcription. |
| 1516 | 20978825 | In obesity-related disorders such as diabetes, metabolic syndrome, and cardiovascular diseases, the circulating levels of CRP and adiponectin are inversely correlated, suggesting that these two factors might reciprocally regulate each other. |
| 1517 | 20978825 | We investigated the possibility that adiponectin inhibits CRP production in HepG(2) cells elicited by IL-6. |
| 1518 | 20978825 | CRP gene expression was determined using ELISA and semi-quantitative RT-PCR, and the phosphorylation of STAT3 was investigated with western blot. |
| 1519 | 20978825 | Adiponectin reduced IL-6-induced CRP mRNA levels in HepG(2) cells and CRP protein secretion. |
| 1520 | 20978825 | Preincubating HepG(2) cells with adiponectin led to a decline in STAT3 phosphorylation on both tyrosine and serine residues. |
| 1521 | 20978825 | Our results demonstrated that adiponectin suppresses CRP synthesis and secretion from HepG(2) cells and suggested that the suppression may be mediated through inhibition of the STAT3 pathway. |
| 1522 | 20978825 | Adiponectin reduces C-reactive protein expression and downregulates STAT3 phosphorylation induced by IL-6 in HepG2 cells. |
| 1523 | 20978825 | CRP is predominately synthesized by hepatocytes when stimulated by interleukin-6 (IL-6). |
| 1524 | 20978825 | In response to IL-6, the signal transducer and activator of transcription 3 (STAT3) becomes phosphorylated on tyrosine and serine residues. |
| 1525 | 20978825 | Phosphorylated STAT3 then activates CRP gene transcription. |
| 1526 | 20978825 | In obesity-related disorders such as diabetes, metabolic syndrome, and cardiovascular diseases, the circulating levels of CRP and adiponectin are inversely correlated, suggesting that these two factors might reciprocally regulate each other. |
| 1527 | 20978825 | We investigated the possibility that adiponectin inhibits CRP production in HepG(2) cells elicited by IL-6. |
| 1528 | 20978825 | CRP gene expression was determined using ELISA and semi-quantitative RT-PCR, and the phosphorylation of STAT3 was investigated with western blot. |
| 1529 | 20978825 | Adiponectin reduced IL-6-induced CRP mRNA levels in HepG(2) cells and CRP protein secretion. |
| 1530 | 20978825 | Preincubating HepG(2) cells with adiponectin led to a decline in STAT3 phosphorylation on both tyrosine and serine residues. |
| 1531 | 20978825 | Our results demonstrated that adiponectin suppresses CRP synthesis and secretion from HepG(2) cells and suggested that the suppression may be mediated through inhibition of the STAT3 pathway. |
| 1532 | 20978825 | Adiponectin reduces C-reactive protein expression and downregulates STAT3 phosphorylation induced by IL-6 in HepG2 cells. |
| 1533 | 20978825 | CRP is predominately synthesized by hepatocytes when stimulated by interleukin-6 (IL-6). |
| 1534 | 20978825 | In response to IL-6, the signal transducer and activator of transcription 3 (STAT3) becomes phosphorylated on tyrosine and serine residues. |
| 1535 | 20978825 | Phosphorylated STAT3 then activates CRP gene transcription. |
| 1536 | 20978825 | In obesity-related disorders such as diabetes, metabolic syndrome, and cardiovascular diseases, the circulating levels of CRP and adiponectin are inversely correlated, suggesting that these two factors might reciprocally regulate each other. |
| 1537 | 20978825 | We investigated the possibility that adiponectin inhibits CRP production in HepG(2) cells elicited by IL-6. |
| 1538 | 20978825 | CRP gene expression was determined using ELISA and semi-quantitative RT-PCR, and the phosphorylation of STAT3 was investigated with western blot. |
| 1539 | 20978825 | Adiponectin reduced IL-6-induced CRP mRNA levels in HepG(2) cells and CRP protein secretion. |
| 1540 | 20978825 | Preincubating HepG(2) cells with adiponectin led to a decline in STAT3 phosphorylation on both tyrosine and serine residues. |
| 1541 | 20978825 | Our results demonstrated that adiponectin suppresses CRP synthesis and secretion from HepG(2) cells and suggested that the suppression may be mediated through inhibition of the STAT3 pathway. |
| 1542 | 21031339 | Leptin injection to TallyHo mice, however, increased the phosphorylation of STAT3 and Akt, an important signaling mediator of leptin, in a pattern similar to that in C57BL/6 mice. |
| 1543 | 21037323 | Cut-like homeobox 1 (CUX1) regulates expression of the fat mass and obesity-associated and retinitis pigmentosa GTPase regulator-interacting protein-1-like (RPGRIP1L) genes and coordinates leptin receptor signaling. |
| 1544 | 21037323 | In an effort to identify the molecular basis for this association, we discovered that FTO and RPGRIP1L (a ciliary gene located in close proximity to the transcriptional start site of FTO) are regulated by isoforms P200 and P110 of the transcription factor, CUX1. |
| 1545 | 21037323 | Promoter-probe analysis revealed that binding of P200 to this site represses FTO, whereas binding of P110 increases transcriptional activity from the FTO as well as RPGRIP1L minimal promoters. |
| 1546 | 21037323 | Reduced expression of Fto or Rpgrip1l affects leptin receptor isoform b trafficking and leptin signaling in N41 mouse hypothalamic or N2a neuroblastoma cells in vitro. |
| 1547 | 21037323 | Leptin receptor clusters in the vicinity of the cilium of arcuate hypothalamic neurons in C57BL/6J mice treated with leptin, but not in fasted mice, suggesting a potentially important role of the cilium in leptin signaling that is, in part, regulated by FTO and RPGRIP1L. |
| 1548 | 21037323 | Decreased Fto/Rpgrip1l expression in the arcuate hypothalamus coincides with decreased nuclear enzymatic activity of a protease (cathepsin L) that has been shown to cleave full-length CUX1 (P200) to P110. |
| 1549 | 21037323 | P200 disrupts (whereas P110 promotes) leptin receptor isoform b clustering in the vicinity of the cilium in vitro. |
| 1550 | 21037323 | Clustering of the receptor coincides with increased leptin signaling as reflected in protein levels of phosphorylated Stat3 (p-Stat3). |
| 1551 | 21037323 | The obesity-risk (A) allele shows reduced affinity for the FTO and RPGRIP1L transcriptional activator P110, leading to the following: 1) decreased FTO and RPGRIP1L mRNA levels; 2) reduced LEPR trafficking to the cilium; and, as a consequence, 3) a diminished cellular response to leptin. |
| 1552 | 21056997 | In the context of the MMTV-PyMT mammary tumor model, the lack of peripheral leptin receptors attenuated tumor progression and metastasis through a reduction of the ERK1/2 and Jak2/STAT3 pathways. |
| 1553 | 21056997 | Leptin receptor-free tumor cells display reduced STAT3 tyrosine phosphorylation on residue Y705 but have increased serine phosphorylation on residue S727, consistent with preserved mitochondrial function in the absence of the leptin receptor. |
| 1554 | 21056997 | In the context of the MMTV-PyMT mammary tumor model, the lack of peripheral leptin receptors attenuated tumor progression and metastasis through a reduction of the ERK1/2 and Jak2/STAT3 pathways. |
| 1555 | 21056997 | Leptin receptor-free tumor cells display reduced STAT3 tyrosine phosphorylation on residue Y705 but have increased serine phosphorylation on residue S727, consistent with preserved mitochondrial function in the absence of the leptin receptor. |
| 1556 | 21103795 | Many obesity-related factors are responsible, including increased blood levels of insulin/IGF, IL-6, TNF-alpha, and leptin, and decreased blood levels of adiponectin. |
| 1557 | 21103795 | IL-17 could activate Src/PI3K, MAPK, Stat3, and PKC, resulting in carcinogenesis. |
| 1558 | 21267512 | Involvement of leptin receptor long isoform (LepRb)-STAT3 signaling pathway in brain fat mass- and obesity-associated (FTO) downregulation during energy restriction. |
| 1559 | 21267512 | Here, we investigated the alternations of FTO mRNA and protein expression in the peripheral metabolic tissues and the brain upon energy restriction (ER) and explored the involvement of the leptin signaling pathway in FTO regulation under ER status. |
| 1560 | 21267512 | Using double-immunofluorescence staining, FTO was found to be colocalized with the leptin receptor long isoform (LepRb) in arcuate nucleus of hypothalamus and the nucleus of the solitary tract. |
| 1561 | 21267512 | Moreover, leptin directly activated the STAT3 signaling pathway and downregulated FTO in in vitro arcuate nucleus of hypothalamus cultures and in vivo wild-type mice but not db/db mice. |
| 1562 | 21267512 | Thus, our results provide the first evidence that the LepRb-STAT3 signaling pathway is involved in the brain FTO downregulation during ER. |
| 1563 | 21267512 | Involvement of leptin receptor long isoform (LepRb)-STAT3 signaling pathway in brain fat mass- and obesity-associated (FTO) downregulation during energy restriction. |
| 1564 | 21267512 | Here, we investigated the alternations of FTO mRNA and protein expression in the peripheral metabolic tissues and the brain upon energy restriction (ER) and explored the involvement of the leptin signaling pathway in FTO regulation under ER status. |
| 1565 | 21267512 | Using double-immunofluorescence staining, FTO was found to be colocalized with the leptin receptor long isoform (LepRb) in arcuate nucleus of hypothalamus and the nucleus of the solitary tract. |
| 1566 | 21267512 | Moreover, leptin directly activated the STAT3 signaling pathway and downregulated FTO in in vitro arcuate nucleus of hypothalamus cultures and in vivo wild-type mice but not db/db mice. |
| 1567 | 21267512 | Thus, our results provide the first evidence that the LepRb-STAT3 signaling pathway is involved in the brain FTO downregulation during ER. |
| 1568 | 21267512 | Involvement of leptin receptor long isoform (LepRb)-STAT3 signaling pathway in brain fat mass- and obesity-associated (FTO) downregulation during energy restriction. |
| 1569 | 21267512 | Here, we investigated the alternations of FTO mRNA and protein expression in the peripheral metabolic tissues and the brain upon energy restriction (ER) and explored the involvement of the leptin signaling pathway in FTO regulation under ER status. |
| 1570 | 21267512 | Using double-immunofluorescence staining, FTO was found to be colocalized with the leptin receptor long isoform (LepRb) in arcuate nucleus of hypothalamus and the nucleus of the solitary tract. |
| 1571 | 21267512 | Moreover, leptin directly activated the STAT3 signaling pathway and downregulated FTO in in vitro arcuate nucleus of hypothalamus cultures and in vivo wild-type mice but not db/db mice. |
| 1572 | 21267512 | Thus, our results provide the first evidence that the LepRb-STAT3 signaling pathway is involved in the brain FTO downregulation during ER. |
| 1573 | 21298325 | Anti-inflammatory effect of insulin in the human hepatoma cell line HepG2 involves decreased transcription of IL-6 target genes and nuclear exclusion of FOXO1. |
| 1574 | 21298325 | The liver is an important target for interleukin-6 (IL-6) action leading to an increased inflammatory response with impaired insulin signaling and action. |
| 1575 | 21298325 | The aims of this study are to address if insulin is anti-inflammatory and attenuates IL-6-induced inflammation in the human hepatoma cell line HepG2 and if this involves signal transducer and activator of transcription 3 (STAT3) signal transduction. |
| 1576 | 21298325 | It was found that insulin significantly reduced IL-6-induced gene transcription of serum amyloid 1 (SAA1), serum amyloid 2 (SAA2), haptoglobin, orosomucoid, and plasmin activator inhibitor-1 (PAI-1). |
| 1577 | 21298325 | However, the authors did not find any evidence that insulin inhibited IL-6 signal transduction, i.e., no effect of insulin was detected on STAT3 phosphorylation or its translocation to cell nucleus. |
| 1578 | 21298325 | Taken together, these results suggest that the anti-inflammatory effect of insulin on IL-6 action is exerted at the level of the transcriptional activation of the genes. |
| 1579 | 21298325 | Further analysis revealed that insulin regulates nuclear localization of FOXO1, which is an important co-activator for STAT3 mediated transcription. |
| 1580 | 21298325 | Insulin induced nuclear exit and Thr24 phosphorylation of FOXO1, thus, inhibiting STAT3-mediated transcription. |
| 1581 | 21298325 | Anti-inflammatory effect of insulin in the human hepatoma cell line HepG2 involves decreased transcription of IL-6 target genes and nuclear exclusion of FOXO1. |
| 1582 | 21298325 | The liver is an important target for interleukin-6 (IL-6) action leading to an increased inflammatory response with impaired insulin signaling and action. |
| 1583 | 21298325 | The aims of this study are to address if insulin is anti-inflammatory and attenuates IL-6-induced inflammation in the human hepatoma cell line HepG2 and if this involves signal transducer and activator of transcription 3 (STAT3) signal transduction. |
| 1584 | 21298325 | It was found that insulin significantly reduced IL-6-induced gene transcription of serum amyloid 1 (SAA1), serum amyloid 2 (SAA2), haptoglobin, orosomucoid, and plasmin activator inhibitor-1 (PAI-1). |
| 1585 | 21298325 | However, the authors did not find any evidence that insulin inhibited IL-6 signal transduction, i.e., no effect of insulin was detected on STAT3 phosphorylation or its translocation to cell nucleus. |
| 1586 | 21298325 | Taken together, these results suggest that the anti-inflammatory effect of insulin on IL-6 action is exerted at the level of the transcriptional activation of the genes. |
| 1587 | 21298325 | Further analysis revealed that insulin regulates nuclear localization of FOXO1, which is an important co-activator for STAT3 mediated transcription. |
| 1588 | 21298325 | Insulin induced nuclear exit and Thr24 phosphorylation of FOXO1, thus, inhibiting STAT3-mediated transcription. |
| 1589 | 21298325 | Anti-inflammatory effect of insulin in the human hepatoma cell line HepG2 involves decreased transcription of IL-6 target genes and nuclear exclusion of FOXO1. |
| 1590 | 21298325 | The liver is an important target for interleukin-6 (IL-6) action leading to an increased inflammatory response with impaired insulin signaling and action. |
| 1591 | 21298325 | The aims of this study are to address if insulin is anti-inflammatory and attenuates IL-6-induced inflammation in the human hepatoma cell line HepG2 and if this involves signal transducer and activator of transcription 3 (STAT3) signal transduction. |
| 1592 | 21298325 | It was found that insulin significantly reduced IL-6-induced gene transcription of serum amyloid 1 (SAA1), serum amyloid 2 (SAA2), haptoglobin, orosomucoid, and plasmin activator inhibitor-1 (PAI-1). |
| 1593 | 21298325 | However, the authors did not find any evidence that insulin inhibited IL-6 signal transduction, i.e., no effect of insulin was detected on STAT3 phosphorylation or its translocation to cell nucleus. |
| 1594 | 21298325 | Taken together, these results suggest that the anti-inflammatory effect of insulin on IL-6 action is exerted at the level of the transcriptional activation of the genes. |
| 1595 | 21298325 | Further analysis revealed that insulin regulates nuclear localization of FOXO1, which is an important co-activator for STAT3 mediated transcription. |
| 1596 | 21298325 | Insulin induced nuclear exit and Thr24 phosphorylation of FOXO1, thus, inhibiting STAT3-mediated transcription. |
| 1597 | 21298325 | Anti-inflammatory effect of insulin in the human hepatoma cell line HepG2 involves decreased transcription of IL-6 target genes and nuclear exclusion of FOXO1. |
| 1598 | 21298325 | The liver is an important target for interleukin-6 (IL-6) action leading to an increased inflammatory response with impaired insulin signaling and action. |
| 1599 | 21298325 | The aims of this study are to address if insulin is anti-inflammatory and attenuates IL-6-induced inflammation in the human hepatoma cell line HepG2 and if this involves signal transducer and activator of transcription 3 (STAT3) signal transduction. |
| 1600 | 21298325 | It was found that insulin significantly reduced IL-6-induced gene transcription of serum amyloid 1 (SAA1), serum amyloid 2 (SAA2), haptoglobin, orosomucoid, and plasmin activator inhibitor-1 (PAI-1). |
| 1601 | 21298325 | However, the authors did not find any evidence that insulin inhibited IL-6 signal transduction, i.e., no effect of insulin was detected on STAT3 phosphorylation or its translocation to cell nucleus. |
| 1602 | 21298325 | Taken together, these results suggest that the anti-inflammatory effect of insulin on IL-6 action is exerted at the level of the transcriptional activation of the genes. |
| 1603 | 21298325 | Further analysis revealed that insulin regulates nuclear localization of FOXO1, which is an important co-activator for STAT3 mediated transcription. |
| 1604 | 21298325 | Insulin induced nuclear exit and Thr24 phosphorylation of FOXO1, thus, inhibiting STAT3-mediated transcription. |
| 1605 | 21300624 | Amongst these are multiple genes involved in IL23/Th17 signalling (IL23R, IL12B, JAK2, TYK2 and STAT3), IL10, IL1R2, REL, CARD9, NKX2.3, ICOSLG, PRDM1, SMAD3 and ORMDL3. |
| 1606 | 21300624 | For Crohn's disease, defective processing of intracellular bacteria has become a central theme, following gene discoveries in autophagy and innate immunity (associations with NOD2, IRGM, ATG16L1 are specific to Crohn's disease). |
| 1607 | 21300624 | Genetic evidence has also demonstrated the importance of barrier function to the development of ulcerative colitis (HNF4A, LAMB1, CDH1 and GNA12). |
| 1608 | 21321316 | A ketogenic diet impairs energy and glucose homeostasis by the attenuation of hypothalamic leptin signaling and hepatic insulin signaling in a rat model of non-obese type 2 diabetes. |
| 1609 | 21321316 | KTD, but not IHB, attenuated hypothalamic signal transducer and activator of transcription 3 and 5'-adenosine monophosphate-activated protein kinase (AMPK) phosphorylation in KTD. |
| 1610 | 21321316 | The increased hepatic glucose output in KTD was associated with increased hepatic phosphoenolpyruvate carboxykinase expression through attenuated tyrosine phosphorylation of IRS2 and phosphorylation of Akt(Ser473). |
| 1611 | 21321316 | In conclusion, KTD impairs energy and glucose homeostasis by exacerbating insulin resistance and attenuating hypothalamic leptin signaling in non-obese type 2 diabetic rats. |
| 1612 | 21364767 | Altered corticosterone, leptin, and adiponectin profiles were also documented in GK animals. |
| 1613 | 21364767 | The GK animals exhibited an age-specific failure to accumulate body fat despite their relatively higher calorie consumption which was well supported by the altered expression of genes involved in adipogenesis and lipogenesis in the white adipose tissue of these animals, including Fasn, Acly, Kklf9, and Stat3. |
| 1614 | 21368653 | Diabetes blockade of sevoflurane postconditioning is not restored by insulin in the rat heart: phosphorylated signal transducer and activator of transcription 3- and phosphatidylinositol 3-kinase-mediated inhibition. |
| 1615 | 21372039 | Abnormal activation of the insulin-like growth factor (IGF)/ IGF-1 receptor (IGF-1R) axis is also involved in obesity-related liver tumorigenesis. |
| 1616 | 21372039 | EGCG inhibited the phosphorylation of the IGF-1R, ERK (extracellular signal-regulated kinase), Akt, GSK-3β (glycogen synthase kinase-3β), Stat3, and JNK (c-Jun NH(2)-terminal kinase) proteins in the livers of experimental mice. |
| 1617 | 21372039 | The serum levels of insulin, IGF-1, IGF-2, free fatty acid, and TNF-α were all decreased by drinking EGCG, which also decreased the expression of TNF-α, interleukin (IL)-6, IL-1β, and IL-18 mRNAs in the livers. |
| 1618 | 21377916 | IL-6 signaling plays a pivotal role in controlling the differentiation and activation of T lymphocytes by inducing the Jak/STAT-3 and the Ras/Erk/C/EBP pathways. |
| 1619 | 21459325 | Adiponectin enhances insulin sensitivity by increasing hepatic IRS-2 expression via a macrophage-derived IL-6-dependent pathway. |
| 1620 | 21459325 | Many actions of adiponectin, a well-recognized antidiabetic adipokine, are currently attributed to the activation of two critical molecules downstream of AdipoR1 and R2: AMP-activated kinase (AMPK) and peroxisome proliferator-activated receptor α (PPARα). |
| 1621 | 21459325 | However, the direct effects of adiponectin on insulin signaling molecules remain poorly understood. |
| 1622 | 21459325 | We show here that adiponectin upregulates IRS-2 through activation of signal transducer and activator of transcription-3 (STAT3). |
| 1623 | 21459325 | Surprisingly, this activation is associated with IL-6 production from macrophages induced by adiponectin through NFκB activation independent of its authentic receptors, AdipoR1 and AdipoR2. |
| 1624 | 21459325 | These data have unraveled an insulin-sensitizing action initiated by adiponectin leading to upregulation of hepatic IRS-2 via an IL-6 dependent pathway through a still unidentified adiponectin receptor. |
| 1625 | 21519350 | Further study revealed that TCV significantly decreased the production of both interleukin (IL)-17 and IL-23 in intrapancreatic infiltrating lymphocytes (IPL) through marked inhibition of mRNA level of retinoic acid-related orphan receptor γt (RORγt) and signal transducer and activator of transcription 3 (Stat3) phosphorylation. |
| 1626 | 21617181 | Activation of peroxisome proliferator-activated receptor-β/-δ (PPAR-β/-δ) ameliorates insulin signaling and reduces SOCS3 levels by inhibiting STAT3 in interleukin-6-stimulated adipocytes. |
| 1627 | 21652728 | Fetal neonatal leptin and insulin deficiency results in reduced hypothalamic axonal pathways regulating appetite, which may predispose to offspring hyperphagia and obesity. |
| 1628 | 21652728 | Neural development of the arcuate nucleus, a key target of adiposity signals, leptin and insulin, is immature at birth. |
| 1629 | 21652728 | Hence, to explore proximate effects of leptin/insulin on hypothalamic development, we determined trophic and differentiation effects on neural stem/progenitor cells using a model of fetal hypothalamic neurospheres (NS). |
| 1630 | 21652728 | NS cultures were produced from embryonic d 20 fetal rats and passage 1 and passage 2 cells examined for proliferation and differentiation into neurons (neuronal nuclei, class IIIβ-tubulin, and doublecortin) and astrocytes (glial fibrillary acidic protein). |
| 1631 | 21652728 | Leptin-induced NS proliferation was significantly greater than that induced by insulin, although both effects were blocked by Notch, extracellular signal-regulated kinase, or signal transducer and activator of transcription 3 inhibition. |
| 1632 | 21652728 | Leptin preferentially induced neuronal, whereas insulin promoted astrocyte differentiation. |
| 1633 | 21652728 | Extracellular signal-regulated kinase inhibition suppressed both leptin and insulin-mediated differentiation, whereas signal transducer and activator of transcription inhibition only affected leptin-mediated responses. |
| 1634 | 21652728 | Altered fetal exposure to leptin or insulin, resulting from fetal growth restriction, macrosomia, or maternal diabetes, may potentially have marked effects on fetal brain development. |
| 1635 | 21747171 | ER activation inhibited β cell lipid synthesis by suppressing the expression (and activity) of fatty acid synthase via a nonclassical pathway dependent on activated Stat3. |
| 1636 | 21776823 | Molecular and cellular studies indicated that metformin significantly elevated p53 and Bax levels and reduced STAT3 and Bcl-2. |
| 1637 | 21776823 | Receptor inhibitor studies indicated that p53 activation was mediated through insulin receptor (IR), not insulin-like growth factor-1 receptor (IGF-IR). |
| 1638 | 21776823 | Furthermore, MEK inhibitor significantly suppressed metformin-induced p53 and Bax elevation while ERK inhibitor generated a slight reduction in p53 levels. |
| 1639 | 21776823 | In contrast, PI3K inhibitor did not produce any effect on the metformin-elevated p53 levels. |
| 1640 | 21776823 | Finally, SAPK/JNK, known to be involved in apoptosis, was activated in cells treated with metformin and the activation appeared to occur downstream of ERK. |
| 1641 | 21776823 | All these results suggested that metformin activated p53, Bax, and induced tumor cell apoptosis through the ERK signaling pathway. |
| 1642 | 21776823 | This pathway has not been previously described for IR, p53, Bax activation, or apoptosis. |
| 1643 | 21822824 | Mechanisms that link these two processes are not completely understood, but transcription factors of the NF-κB family and signal transducer and activator of transcription 3 (STAT3), cytokines such as IL-6 and IL-1α and ligands of the epidermal growth factor receptor (EGFR) family are clearly pivotal players. |
| 1644 | 21953375 | Analysis of mRNA sequencing data identified that treatment of keratinocytes with 20 μM hydroxytyrosol results in the upregulation of numerous antioxidant proteins and enzymes, including heme oxygenase-1 (15.46-fold upregulation), glutaredoxin (1.65) and glutathione peroxidase (1.53). |
| 1645 | 21953375 | These include changes in the expression of STAT3, STAT6, SMAD7 and ETS-1. |
| 1646 | 22069265 | Interleukin-6 treatment induces beta-cell apoptosis via STAT-3-mediated nitric oxide production. |
| 1647 | 22110483 | TNFα induces vascular inflammation, monocyte adhesion to endothelial cells, vascular oxidative stress, apoptosis, and atherogenic response and participates in the regulation of thrombosis and coagulation through multiple signaling pathways involving NFκB, Sp1, activator protein 1, JNK, p38, STAT3, and so forth. |
| 1648 | 22178606 | We report here that high glucose (HG) treatment stimulated astrocytic morphological alteration coupled with changes in glial fibrillary acidic protein (GFAP) and vimentin expression. |
| 1649 | 22178606 | Additionally, HG upregulated the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), interleukin-4 (IL-4), and vascular endothelial growth factor (VEGF); however, its effects on transforming growth factor-β (TGF-β) expression were not evident. |
| 1650 | 22178606 | HG treatment induced increased production of reactive oxygen species (ROS) as well as activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator transcription 3 (STAT 3). |
| 1651 | 22178606 | HG-induced expression of TNF-α, IL-6, IL-1β, IL-4, and VEGF was blocked by ROS scavenger and inhibitors specific for NF-κB and STAT 3, respectively. |
| 1652 | 22178606 | We report here that high glucose (HG) treatment stimulated astrocytic morphological alteration coupled with changes in glial fibrillary acidic protein (GFAP) and vimentin expression. |
| 1653 | 22178606 | Additionally, HG upregulated the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), interleukin-4 (IL-4), and vascular endothelial growth factor (VEGF); however, its effects on transforming growth factor-β (TGF-β) expression were not evident. |
| 1654 | 22178606 | HG treatment induced increased production of reactive oxygen species (ROS) as well as activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator transcription 3 (STAT 3). |
| 1655 | 22178606 | HG-induced expression of TNF-α, IL-6, IL-1β, IL-4, and VEGF was blocked by ROS scavenger and inhibitors specific for NF-κB and STAT 3, respectively. |
| 1656 | 22276206 | Over-expression of leptin receptors in hypothalamic POMC neurons increases susceptibility to diet-induced obesity. |
| 1657 | 22276206 | Diet-induced obesity (DIO) in rodents is characterized by impaired activation of signal-transducer and activator of transcription 3 (STAT3) by leptin receptors (LepRb) within the hypothalamic arcuate nucleus. |
| 1658 | 22276206 | However, the neuro-chemical identity of the leptin-STAT3 resistant arcuate neurons has not been determined and the underlying mechanisms responsible for development of cellular leptin resistance remain unclear. |
| 1659 | 22276206 | To investigate this, we first measured arcuate gene expression of known key signaling components of the LepRb signaling pathway and tested whether specifically the critical arcuate pro-opiomelanocortin (POMC) neurons are resistant to LepRb-STAT3 signaling in mice given a high-fat-diet (HFD) compared to mice provided a low-fat control diet (LFD). |
| 1660 | 22276206 | We found that leptin-dependent STAT3 phosphorylation was decreased within POMC neurons of HFD mice. |
| 1661 | 22276206 | To investigate whether increased LepRb expression per se in POMC neurons can influence development of DIO and Socs3 expression, we created mice that over-express LepRb selectively in POMC neurons (POMC-LepRb). |
| 1662 | 22276206 | These data show that specifically POMC neurons of DIO mice are resistant to STAT3 activation by leptin, indicating that those cells might play a role in development of DIO. |
| 1663 | 22276206 | Over-expression of leptin receptors in hypothalamic POMC neurons increases susceptibility to diet-induced obesity. |
| 1664 | 22276206 | Diet-induced obesity (DIO) in rodents is characterized by impaired activation of signal-transducer and activator of transcription 3 (STAT3) by leptin receptors (LepRb) within the hypothalamic arcuate nucleus. |
| 1665 | 22276206 | However, the neuro-chemical identity of the leptin-STAT3 resistant arcuate neurons has not been determined and the underlying mechanisms responsible for development of cellular leptin resistance remain unclear. |
| 1666 | 22276206 | To investigate this, we first measured arcuate gene expression of known key signaling components of the LepRb signaling pathway and tested whether specifically the critical arcuate pro-opiomelanocortin (POMC) neurons are resistant to LepRb-STAT3 signaling in mice given a high-fat-diet (HFD) compared to mice provided a low-fat control diet (LFD). |
| 1667 | 22276206 | We found that leptin-dependent STAT3 phosphorylation was decreased within POMC neurons of HFD mice. |
| 1668 | 22276206 | To investigate whether increased LepRb expression per se in POMC neurons can influence development of DIO and Socs3 expression, we created mice that over-express LepRb selectively in POMC neurons (POMC-LepRb). |
| 1669 | 22276206 | These data show that specifically POMC neurons of DIO mice are resistant to STAT3 activation by leptin, indicating that those cells might play a role in development of DIO. |
| 1670 | 22276206 | Over-expression of leptin receptors in hypothalamic POMC neurons increases susceptibility to diet-induced obesity. |
| 1671 | 22276206 | Diet-induced obesity (DIO) in rodents is characterized by impaired activation of signal-transducer and activator of transcription 3 (STAT3) by leptin receptors (LepRb) within the hypothalamic arcuate nucleus. |
| 1672 | 22276206 | However, the neuro-chemical identity of the leptin-STAT3 resistant arcuate neurons has not been determined and the underlying mechanisms responsible for development of cellular leptin resistance remain unclear. |
| 1673 | 22276206 | To investigate this, we first measured arcuate gene expression of known key signaling components of the LepRb signaling pathway and tested whether specifically the critical arcuate pro-opiomelanocortin (POMC) neurons are resistant to LepRb-STAT3 signaling in mice given a high-fat-diet (HFD) compared to mice provided a low-fat control diet (LFD). |
| 1674 | 22276206 | We found that leptin-dependent STAT3 phosphorylation was decreased within POMC neurons of HFD mice. |
| 1675 | 22276206 | To investigate whether increased LepRb expression per se in POMC neurons can influence development of DIO and Socs3 expression, we created mice that over-express LepRb selectively in POMC neurons (POMC-LepRb). |
| 1676 | 22276206 | These data show that specifically POMC neurons of DIO mice are resistant to STAT3 activation by leptin, indicating that those cells might play a role in development of DIO. |
| 1677 | 22276206 | Over-expression of leptin receptors in hypothalamic POMC neurons increases susceptibility to diet-induced obesity. |
| 1678 | 22276206 | Diet-induced obesity (DIO) in rodents is characterized by impaired activation of signal-transducer and activator of transcription 3 (STAT3) by leptin receptors (LepRb) within the hypothalamic arcuate nucleus. |
| 1679 | 22276206 | However, the neuro-chemical identity of the leptin-STAT3 resistant arcuate neurons has not been determined and the underlying mechanisms responsible for development of cellular leptin resistance remain unclear. |
| 1680 | 22276206 | To investigate this, we first measured arcuate gene expression of known key signaling components of the LepRb signaling pathway and tested whether specifically the critical arcuate pro-opiomelanocortin (POMC) neurons are resistant to LepRb-STAT3 signaling in mice given a high-fat-diet (HFD) compared to mice provided a low-fat control diet (LFD). |
| 1681 | 22276206 | We found that leptin-dependent STAT3 phosphorylation was decreased within POMC neurons of HFD mice. |
| 1682 | 22276206 | To investigate whether increased LepRb expression per se in POMC neurons can influence development of DIO and Socs3 expression, we created mice that over-express LepRb selectively in POMC neurons (POMC-LepRb). |
| 1683 | 22276206 | These data show that specifically POMC neurons of DIO mice are resistant to STAT3 activation by leptin, indicating that those cells might play a role in development of DIO. |
| 1684 | 22276206 | Over-expression of leptin receptors in hypothalamic POMC neurons increases susceptibility to diet-induced obesity. |
| 1685 | 22276206 | Diet-induced obesity (DIO) in rodents is characterized by impaired activation of signal-transducer and activator of transcription 3 (STAT3) by leptin receptors (LepRb) within the hypothalamic arcuate nucleus. |
| 1686 | 22276206 | However, the neuro-chemical identity of the leptin-STAT3 resistant arcuate neurons has not been determined and the underlying mechanisms responsible for development of cellular leptin resistance remain unclear. |
| 1687 | 22276206 | To investigate this, we first measured arcuate gene expression of known key signaling components of the LepRb signaling pathway and tested whether specifically the critical arcuate pro-opiomelanocortin (POMC) neurons are resistant to LepRb-STAT3 signaling in mice given a high-fat-diet (HFD) compared to mice provided a low-fat control diet (LFD). |
| 1688 | 22276206 | We found that leptin-dependent STAT3 phosphorylation was decreased within POMC neurons of HFD mice. |
| 1689 | 22276206 | To investigate whether increased LepRb expression per se in POMC neurons can influence development of DIO and Socs3 expression, we created mice that over-express LepRb selectively in POMC neurons (POMC-LepRb). |
| 1690 | 22276206 | These data show that specifically POMC neurons of DIO mice are resistant to STAT3 activation by leptin, indicating that those cells might play a role in development of DIO. |
| 1691 | 22366233 | Selenate enhances STAT3 transcriptional activity in endothelial cells: differential actions of selenate and selenite on LIF cytokine signaling and cell viability. |
| 1692 | 22366233 | We report that treatment of human microvascular endothelial cells with sodium selenate at a pharmacological dose (100 μM) enhanced tyrosine phosphorylation of nuclear STAT3 on Y705 in response to IL-6-type cytokine, leukemia inhibitory factor (LIF), indicative of enhanced STAT3 activity. |
| 1693 | 22366233 | Accordingly, STAT3 nuclear binding to DNA was increased, as well as LIF-induced gene expression of chemokine (C-C motif) ligand 2 (CCL2). |
| 1694 | 22366233 | The enhancing action of selenate on LIF-induced STAT3 Y705 phosphorylation was replicated by vanadate and a specific inhibitor of protein tyrosine phosphatase, non-receptor type 1 (PTP1B). |
| 1695 | 22366233 | Our findings support the conclusion that in human microvascular endothelial cells selenate has a vanadate-like effect in inhibiting PTP1B and enhancing proinflammatory STAT3 activation. |
| 1696 | 22366233 | Selenate enhances STAT3 transcriptional activity in endothelial cells: differential actions of selenate and selenite on LIF cytokine signaling and cell viability. |
| 1697 | 22366233 | We report that treatment of human microvascular endothelial cells with sodium selenate at a pharmacological dose (100 μM) enhanced tyrosine phosphorylation of nuclear STAT3 on Y705 in response to IL-6-type cytokine, leukemia inhibitory factor (LIF), indicative of enhanced STAT3 activity. |
| 1698 | 22366233 | Accordingly, STAT3 nuclear binding to DNA was increased, as well as LIF-induced gene expression of chemokine (C-C motif) ligand 2 (CCL2). |
| 1699 | 22366233 | The enhancing action of selenate on LIF-induced STAT3 Y705 phosphorylation was replicated by vanadate and a specific inhibitor of protein tyrosine phosphatase, non-receptor type 1 (PTP1B). |
| 1700 | 22366233 | Our findings support the conclusion that in human microvascular endothelial cells selenate has a vanadate-like effect in inhibiting PTP1B and enhancing proinflammatory STAT3 activation. |
| 1701 | 22366233 | Selenate enhances STAT3 transcriptional activity in endothelial cells: differential actions of selenate and selenite on LIF cytokine signaling and cell viability. |
| 1702 | 22366233 | We report that treatment of human microvascular endothelial cells with sodium selenate at a pharmacological dose (100 μM) enhanced tyrosine phosphorylation of nuclear STAT3 on Y705 in response to IL-6-type cytokine, leukemia inhibitory factor (LIF), indicative of enhanced STAT3 activity. |
| 1703 | 22366233 | Accordingly, STAT3 nuclear binding to DNA was increased, as well as LIF-induced gene expression of chemokine (C-C motif) ligand 2 (CCL2). |
| 1704 | 22366233 | The enhancing action of selenate on LIF-induced STAT3 Y705 phosphorylation was replicated by vanadate and a specific inhibitor of protein tyrosine phosphatase, non-receptor type 1 (PTP1B). |
| 1705 | 22366233 | Our findings support the conclusion that in human microvascular endothelial cells selenate has a vanadate-like effect in inhibiting PTP1B and enhancing proinflammatory STAT3 activation. |
| 1706 | 22366233 | Selenate enhances STAT3 transcriptional activity in endothelial cells: differential actions of selenate and selenite on LIF cytokine signaling and cell viability. |
| 1707 | 22366233 | We report that treatment of human microvascular endothelial cells with sodium selenate at a pharmacological dose (100 μM) enhanced tyrosine phosphorylation of nuclear STAT3 on Y705 in response to IL-6-type cytokine, leukemia inhibitory factor (LIF), indicative of enhanced STAT3 activity. |
| 1708 | 22366233 | Accordingly, STAT3 nuclear binding to DNA was increased, as well as LIF-induced gene expression of chemokine (C-C motif) ligand 2 (CCL2). |
| 1709 | 22366233 | The enhancing action of selenate on LIF-induced STAT3 Y705 phosphorylation was replicated by vanadate and a specific inhibitor of protein tyrosine phosphatase, non-receptor type 1 (PTP1B). |
| 1710 | 22366233 | Our findings support the conclusion that in human microvascular endothelial cells selenate has a vanadate-like effect in inhibiting PTP1B and enhancing proinflammatory STAT3 activation. |
| 1711 | 22366233 | Selenate enhances STAT3 transcriptional activity in endothelial cells: differential actions of selenate and selenite on LIF cytokine signaling and cell viability. |
| 1712 | 22366233 | We report that treatment of human microvascular endothelial cells with sodium selenate at a pharmacological dose (100 μM) enhanced tyrosine phosphorylation of nuclear STAT3 on Y705 in response to IL-6-type cytokine, leukemia inhibitory factor (LIF), indicative of enhanced STAT3 activity. |
| 1713 | 22366233 | Accordingly, STAT3 nuclear binding to DNA was increased, as well as LIF-induced gene expression of chemokine (C-C motif) ligand 2 (CCL2). |
| 1714 | 22366233 | The enhancing action of selenate on LIF-induced STAT3 Y705 phosphorylation was replicated by vanadate and a specific inhibitor of protein tyrosine phosphatase, non-receptor type 1 (PTP1B). |
| 1715 | 22366233 | Our findings support the conclusion that in human microvascular endothelial cells selenate has a vanadate-like effect in inhibiting PTP1B and enhancing proinflammatory STAT3 activation. |
| 1716 | 22508064 | We observed that the diabetic mice exhibited delayed wound closure characterized by a significant reduction in collagen deposition, prolonged elevation in inflammatory cytokines, aberrant activation of STAT3 and reduction in the activation of Akt and NF-κB when compared with the control mice. |
| 1717 | 22508064 | Moreover, in the diabetic mice, the wound-resident macrophages were dysfunctional and demonstrated increased apoptosis, a significant reduction in their phagocytotic ability, aberrant activation of STAT3 and a marked reduction in the activation of Akt. |
| 1718 | 22508064 | Interestingly, the supplementation of diabetic mice with WP significantly enhanced the collagen deposition, limited the inflammatory stimuli, restored the activation of STAT3, Akt and NF-κB and greatly improved the closure of diabetic wounds compared with the control mice. |
| 1719 | 22508064 | We observed that the diabetic mice exhibited delayed wound closure characterized by a significant reduction in collagen deposition, prolonged elevation in inflammatory cytokines, aberrant activation of STAT3 and reduction in the activation of Akt and NF-κB when compared with the control mice. |
| 1720 | 22508064 | Moreover, in the diabetic mice, the wound-resident macrophages were dysfunctional and demonstrated increased apoptosis, a significant reduction in their phagocytotic ability, aberrant activation of STAT3 and a marked reduction in the activation of Akt. |
| 1721 | 22508064 | Interestingly, the supplementation of diabetic mice with WP significantly enhanced the collagen deposition, limited the inflammatory stimuli, restored the activation of STAT3, Akt and NF-κB and greatly improved the closure of diabetic wounds compared with the control mice. |
| 1722 | 22508064 | We observed that the diabetic mice exhibited delayed wound closure characterized by a significant reduction in collagen deposition, prolonged elevation in inflammatory cytokines, aberrant activation of STAT3 and reduction in the activation of Akt and NF-κB when compared with the control mice. |
| 1723 | 22508064 | Moreover, in the diabetic mice, the wound-resident macrophages were dysfunctional and demonstrated increased apoptosis, a significant reduction in their phagocytotic ability, aberrant activation of STAT3 and a marked reduction in the activation of Akt. |
| 1724 | 22508064 | Interestingly, the supplementation of diabetic mice with WP significantly enhanced the collagen deposition, limited the inflammatory stimuli, restored the activation of STAT3, Akt and NF-κB and greatly improved the closure of diabetic wounds compared with the control mice. |
| 1725 | 22522613 | Amyloid-β induces hepatic insulin resistance by activating JAK2/STAT3/SOCS-1 signaling pathway. |
| 1726 | 22522613 | Aβ can upregulate suppressors of cytokine signaling (SOCS)-1, a well-known insulin signaling inhibitor. |
| 1727 | 22522613 | Knockdown of SOCS-1 alleviates Aβ-induced impairment of insulin signaling. |
| 1728 | 22522613 | Moreover, JAK2/STAT3 is activated by Aβ, and inhibition of JAK2/STAT3 signaling attenuates Aβ-induced upregulation of SOCS-1 and insulin resistance in hepatocytes. |
| 1729 | 22522613 | Our results demonstrate that Aβ induces hepatic insulin resistance by activating JAK2/STAT3/SOCS-1 signaling pathway and have implications toward resolving insulin resistance and T2DM. |
| 1730 | 22522613 | Amyloid-β induces hepatic insulin resistance by activating JAK2/STAT3/SOCS-1 signaling pathway. |
| 1731 | 22522613 | Aβ can upregulate suppressors of cytokine signaling (SOCS)-1, a well-known insulin signaling inhibitor. |
| 1732 | 22522613 | Knockdown of SOCS-1 alleviates Aβ-induced impairment of insulin signaling. |
| 1733 | 22522613 | Moreover, JAK2/STAT3 is activated by Aβ, and inhibition of JAK2/STAT3 signaling attenuates Aβ-induced upregulation of SOCS-1 and insulin resistance in hepatocytes. |
| 1734 | 22522613 | Our results demonstrate that Aβ induces hepatic insulin resistance by activating JAK2/STAT3/SOCS-1 signaling pathway and have implications toward resolving insulin resistance and T2DM. |
| 1735 | 22522613 | Amyloid-β induces hepatic insulin resistance by activating JAK2/STAT3/SOCS-1 signaling pathway. |
| 1736 | 22522613 | Aβ can upregulate suppressors of cytokine signaling (SOCS)-1, a well-known insulin signaling inhibitor. |
| 1737 | 22522613 | Knockdown of SOCS-1 alleviates Aβ-induced impairment of insulin signaling. |
| 1738 | 22522613 | Moreover, JAK2/STAT3 is activated by Aβ, and inhibition of JAK2/STAT3 signaling attenuates Aβ-induced upregulation of SOCS-1 and insulin resistance in hepatocytes. |
| 1739 | 22522613 | Our results demonstrate that Aβ induces hepatic insulin resistance by activating JAK2/STAT3/SOCS-1 signaling pathway and have implications toward resolving insulin resistance and T2DM. |
| 1740 | 22539679 | Uterine production of leukemia inhibitory factor (LIF) and phosphorylation of uterine NFkappaBp65 and STAT3-Ty705 were found to be low (P < 0.01) during Day 4.5 postcoitum, whereas IFNgamma was aberrantly overexpressed. |
| 1741 | 22539679 | Loss of temporal regulation of progesterone receptor A (PR A) and PR B, together with aberrantly increased expression of the protein inhibitor of activated STAT-y (PIASy) (P < 0.01) and reduced recruitment (P < 0.01) of the latter to nuclear progesterone receptor sites were prominent features of decidualization failure occurring at peri-implantation in dNOD mice. |
| 1742 | 22543247 | In vivo, in mouse islets, ERα activation inhibited β-cell lipogenesis by suppressing fatty acid synthase expression (and activity) via an extranuclear, estrogen response element (ERE)-independent pathway requiring the signal transducer and activator of transcription 3. |
| 1743 | 22564979 | We show that E2, and pharmacological agonists for ERα, ERβ, and the G protein-coupled ER, suppress mRNA and protein expression of the transcriptional regulators of FAS, namely, sterol regulatory element-binding protein 1c (SREBP1c) and carbohydrate response element binding protein (ChREBP) in insulin-secreting INS-1 cells. |
| 1744 | 22564979 | Using two mouse lines with pancreas-specific null deletion of either ERα or the signal transducer and activator of transcription 3 (STAT3), we show that ERα activation in vivo reduces SREBP1c and ChREBP mRNA expression via a direct islet action involving STAT3 activation. |
| 1745 | 22564979 | The master regulators of lipogenesis, liver X receptor (LXR) α and β, transcriptionally up-regulate SREBP1c and ChREBP. |
| 1746 | 22564979 | Finally, we show that E2 also activates and uses AMP-activated protein kinase in INS-1 cells to suppress SREBP1c protein expression. |
| 1747 | 22564979 | This study identifies extranuclear ER pathways involving STAT3 and AMP-activated protein kinase in the genetic control of lipogenesis with therapeutic implications to protect β-cells in type 2 diabetes. |
| 1748 | 22564979 | We show that E2, and pharmacological agonists for ERα, ERβ, and the G protein-coupled ER, suppress mRNA and protein expression of the transcriptional regulators of FAS, namely, sterol regulatory element-binding protein 1c (SREBP1c) and carbohydrate response element binding protein (ChREBP) in insulin-secreting INS-1 cells. |
| 1749 | 22564979 | Using two mouse lines with pancreas-specific null deletion of either ERα or the signal transducer and activator of transcription 3 (STAT3), we show that ERα activation in vivo reduces SREBP1c and ChREBP mRNA expression via a direct islet action involving STAT3 activation. |
| 1750 | 22564979 | The master regulators of lipogenesis, liver X receptor (LXR) α and β, transcriptionally up-regulate SREBP1c and ChREBP. |
| 1751 | 22564979 | Finally, we show that E2 also activates and uses AMP-activated protein kinase in INS-1 cells to suppress SREBP1c protein expression. |
| 1752 | 22564979 | This study identifies extranuclear ER pathways involving STAT3 and AMP-activated protein kinase in the genetic control of lipogenesis with therapeutic implications to protect β-cells in type 2 diabetes. |
| 1753 | 22649064 | The mRNA and protein expressions of LIF and its receptor (LIFR) were measured in skeletal muscle biopsies from healthy individuals and patients with type 2 diabetes by use of qPCR and Western blot. |
| 1754 | 22649064 | LIF signaling and response were studied following administration of recombinant LIF and siRNA knockdown of suppressor of cytokine signaling (SOCS)3 in myoblast cultures established from healthy individuals and patients with type 2 diabetes. |
| 1755 | 22649064 | LIF and LIFR proteins were increased in both muscle tissue and cultured myoblasts from diabetic patients. |
| 1756 | 22649064 | Nonetheless, in the diabetic myoblasts, LIF-induced phosphorylation of signal transducer and activator of transcription (STAT)1 and STAT3 was impaired. |
| 1757 | 22649064 | The deficient response to LIF administration in the diabetic myoblasts was further emphasized by a lack of increase in LIF-stimulated cell proliferation and a decreased LIF-stimulated induction of the proliferation-promoting factors cyclin D1, JunB, and c-myc. |
| 1758 | 22649064 | SOCS3 protein was upregulated in diabetic myoblasts, and knockdown of SOCS3 rescued LIF-induced gene expression in diabetic myoblasts, whereas neither STAT1 or STAT3 signaling nor proliferation rate was affected. |
| 1759 | 22649064 | In conclusion, although LIF and LIFR proteins were increased in muscle tissue and myoblasts from diabetic patients, LIF signaling and LIF-stimulated cell proliferation were impaired in diabetic myoblasts, suggesting a novel mechanism by which muscle function is compromised in diabetes. |
| 1760 | 22649064 | The mRNA and protein expressions of LIF and its receptor (LIFR) were measured in skeletal muscle biopsies from healthy individuals and patients with type 2 diabetes by use of qPCR and Western blot. |
| 1761 | 22649064 | LIF signaling and response were studied following administration of recombinant LIF and siRNA knockdown of suppressor of cytokine signaling (SOCS)3 in myoblast cultures established from healthy individuals and patients with type 2 diabetes. |
| 1762 | 22649064 | LIF and LIFR proteins were increased in both muscle tissue and cultured myoblasts from diabetic patients. |
| 1763 | 22649064 | Nonetheless, in the diabetic myoblasts, LIF-induced phosphorylation of signal transducer and activator of transcription (STAT)1 and STAT3 was impaired. |
| 1764 | 22649064 | The deficient response to LIF administration in the diabetic myoblasts was further emphasized by a lack of increase in LIF-stimulated cell proliferation and a decreased LIF-stimulated induction of the proliferation-promoting factors cyclin D1, JunB, and c-myc. |
| 1765 | 22649064 | SOCS3 protein was upregulated in diabetic myoblasts, and knockdown of SOCS3 rescued LIF-induced gene expression in diabetic myoblasts, whereas neither STAT1 or STAT3 signaling nor proliferation rate was affected. |
| 1766 | 22649064 | In conclusion, although LIF and LIFR proteins were increased in muscle tissue and myoblasts from diabetic patients, LIF signaling and LIF-stimulated cell proliferation were impaired in diabetic myoblasts, suggesting a novel mechanism by which muscle function is compromised in diabetes. |
| 1767 | 22660795 | Activating transcription factor 4 mediates hyperglycaemia-induced endothelial inflammation and retinal vascular leakage through activation of STAT3 in a mouse model of type 1 diabetes. |
| 1768 | 22722139 | AGER/RAGE-mediated autophagy promotes pancreatic tumorigenesis and bioenergetics through the IL6-pSTAT3 pathway. |
| 1769 | 22722139 | Pancreatic ductal adenocarcinoma (PDA), the fourth leading cause of cancer death in the United States, is a complex disease that arises in the setting of genetic alterations (KRAS, BRCA1, SMAD4, CDKN2A/p16 (INK4a) and TP53), epigenetic perturbations (MIR155, acetylation and methylation) and epicellular events (diabetes and inflammation). |
| 1770 | 22722139 | In pancreatic tumor cell lines, AGER-mediated autophagy promotes interleukin-6 (IL6)-induced phosphorylation of signal transducer and activator of transcription 3 (pSTAT3) and mitochondrial localization of pSTAT3. |
| 1771 | 22722139 | Moreover, we observed a positive feedback loop between activation of autophagy and the IL6-pSTAT3 pathway, perhaps different from the role of cytosolic nonphosphorylated STAT3, which has been reported to inhibit autophagy. |
| 1772 | 22722139 | Thus, AGER is an important inflammatory mediator that modulates crosstalk between prosurvival pathways, IL6-pSTAT3 and autophagy, in PDA tumor cells, and contributes to early PanIN formation. |
| 1773 | 22722139 | AGER/RAGE-mediated autophagy promotes pancreatic tumorigenesis and bioenergetics through the IL6-pSTAT3 pathway. |
| 1774 | 22722139 | Pancreatic ductal adenocarcinoma (PDA), the fourth leading cause of cancer death in the United States, is a complex disease that arises in the setting of genetic alterations (KRAS, BRCA1, SMAD4, CDKN2A/p16 (INK4a) and TP53), epigenetic perturbations (MIR155, acetylation and methylation) and epicellular events (diabetes and inflammation). |
| 1775 | 22722139 | In pancreatic tumor cell lines, AGER-mediated autophagy promotes interleukin-6 (IL6)-induced phosphorylation of signal transducer and activator of transcription 3 (pSTAT3) and mitochondrial localization of pSTAT3. |
| 1776 | 22722139 | Moreover, we observed a positive feedback loop between activation of autophagy and the IL6-pSTAT3 pathway, perhaps different from the role of cytosolic nonphosphorylated STAT3, which has been reported to inhibit autophagy. |
| 1777 | 22722139 | Thus, AGER is an important inflammatory mediator that modulates crosstalk between prosurvival pathways, IL6-pSTAT3 and autophagy, in PDA tumor cells, and contributes to early PanIN formation. |
| 1778 | 22736507 | Liquid chromatography-tandem mass spectroscopy-based analysis revealed increases in urinary proteins that are early indicators of DN (e.g., cystatin C, clusterin, cathepsin B, retinol binding protein 4, and peroxiredoxin-1) in the STZ group, which were blocked by suramin. |
| 1779 | 22736507 | Endothelial intracellular adhesion molecule-1 (ICAM-1) activation, leukocyte infiltration, and inflammation; transforming growth factor-β1 (TGF-β1) signaling; TGF-β1/SMAD-3-activated fibrogenic markers fibronectin-1, α-smooth muscle actin, and collagen 1A2; activation of proinflammatory and profibrotic transcription factors nuclear factor-κB (NF-κB) and signal transducer and activator of transcription factor-3 (STAT-3), respectively, were all increased in STZ rats and suramin blocked these changes. |
| 1780 | 22736507 | In conclusion, delayed administration of suramin attenuated 1) urinary markers of DN, 2) inflammation by blocking NF-κB activation and ICAM-1-mediated leukocyte infiltration, and 3) fibrosis by blocking STAT-3 and TGF-β1/SMAD-3 signaling. |
| 1781 | 22736507 | Liquid chromatography-tandem mass spectroscopy-based analysis revealed increases in urinary proteins that are early indicators of DN (e.g., cystatin C, clusterin, cathepsin B, retinol binding protein 4, and peroxiredoxin-1) in the STZ group, which were blocked by suramin. |
| 1782 | 22736507 | Endothelial intracellular adhesion molecule-1 (ICAM-1) activation, leukocyte infiltration, and inflammation; transforming growth factor-β1 (TGF-β1) signaling; TGF-β1/SMAD-3-activated fibrogenic markers fibronectin-1, α-smooth muscle actin, and collagen 1A2; activation of proinflammatory and profibrotic transcription factors nuclear factor-κB (NF-κB) and signal transducer and activator of transcription factor-3 (STAT-3), respectively, were all increased in STZ rats and suramin blocked these changes. |
| 1783 | 22736507 | In conclusion, delayed administration of suramin attenuated 1) urinary markers of DN, 2) inflammation by blocking NF-κB activation and ICAM-1-mediated leukocyte infiltration, and 3) fibrosis by blocking STAT-3 and TGF-β1/SMAD-3 signaling. |
| 1784 | 22745068 | Total glucosides of paeony regulates JAK2/STAT3 activation and macrophage proliferation in diabetic rat kidneys. |
| 1785 | 22745068 | Herein, we investigated the ability of TGP to modulate JAK2/STAT3 activation and macrophage proliferation in rats with streptozotocin (STZ)-induced diabetes. |
| 1786 | 22745068 | Immunohistochemistry and double immunohistochemistry were used to identify p-STAT3, ED-1, PCNA/ED-1, and p-STAT3/ED-1-positive (+) cells. |
| 1787 | 22745068 | These results show that TGP significantly inhibited diabetic nephropathy progression and suggest that these protective effects are associated with the ability of TGP to inhibit the JAK2/STAT3 pathway and macrophage proliferation and action. |
| 1788 | 22745068 | Total glucosides of paeony regulates JAK2/STAT3 activation and macrophage proliferation in diabetic rat kidneys. |
| 1789 | 22745068 | Herein, we investigated the ability of TGP to modulate JAK2/STAT3 activation and macrophage proliferation in rats with streptozotocin (STZ)-induced diabetes. |
| 1790 | 22745068 | Immunohistochemistry and double immunohistochemistry were used to identify p-STAT3, ED-1, PCNA/ED-1, and p-STAT3/ED-1-positive (+) cells. |
| 1791 | 22745068 | These results show that TGP significantly inhibited diabetic nephropathy progression and suggest that these protective effects are associated with the ability of TGP to inhibit the JAK2/STAT3 pathway and macrophage proliferation and action. |
| 1792 | 22745068 | Total glucosides of paeony regulates JAK2/STAT3 activation and macrophage proliferation in diabetic rat kidneys. |
| 1793 | 22745068 | Herein, we investigated the ability of TGP to modulate JAK2/STAT3 activation and macrophage proliferation in rats with streptozotocin (STZ)-induced diabetes. |
| 1794 | 22745068 | Immunohistochemistry and double immunohistochemistry were used to identify p-STAT3, ED-1, PCNA/ED-1, and p-STAT3/ED-1-positive (+) cells. |
| 1795 | 22745068 | These results show that TGP significantly inhibited diabetic nephropathy progression and suggest that these protective effects are associated with the ability of TGP to inhibit the JAK2/STAT3 pathway and macrophage proliferation and action. |
| 1796 | 22745068 | Total glucosides of paeony regulates JAK2/STAT3 activation and macrophage proliferation in diabetic rat kidneys. |
| 1797 | 22745068 | Herein, we investigated the ability of TGP to modulate JAK2/STAT3 activation and macrophage proliferation in rats with streptozotocin (STZ)-induced diabetes. |
| 1798 | 22745068 | Immunohistochemistry and double immunohistochemistry were used to identify p-STAT3, ED-1, PCNA/ED-1, and p-STAT3/ED-1-positive (+) cells. |
| 1799 | 22745068 | These results show that TGP significantly inhibited diabetic nephropathy progression and suggest that these protective effects are associated with the ability of TGP to inhibit the JAK2/STAT3 pathway and macrophage proliferation and action. |
| 1800 | 22745922 | Mouse skeletal muscle fiber-type-specific macroautophagy and muscle wasting are regulated by a Fyn/STAT3/Vps34 signaling pathway. |
| 1801 | 22745922 | This was due to inhibition of macroautophagy via an mTORC1-independent but STAT3-dependent reduction in Vps34 protein levels and decreased Vps34/p150/Beclin1/Atg14 complex 1. |
| 1802 | 22745922 | In parallel, Y705-STAT3 phosphorylation increased with decreased Vps34 protein levels. |
| 1803 | 22745922 | Moreover, fed/starved regulation of Y705-STAT3 phosphorylation and Vps34 protein levels was prevented in skeletal muscle of Fyn null mice. |
| 1804 | 22745922 | These data demonstrate a Fyn/STAT3/Vps34 pathway that is responsible for fiber-type-specific regulation of macroautophagy and skeletal muscle atrophy. |
| 1805 | 22745922 | Mouse skeletal muscle fiber-type-specific macroautophagy and muscle wasting are regulated by a Fyn/STAT3/Vps34 signaling pathway. |
| 1806 | 22745922 | This was due to inhibition of macroautophagy via an mTORC1-independent but STAT3-dependent reduction in Vps34 protein levels and decreased Vps34/p150/Beclin1/Atg14 complex 1. |
| 1807 | 22745922 | In parallel, Y705-STAT3 phosphorylation increased with decreased Vps34 protein levels. |
| 1808 | 22745922 | Moreover, fed/starved regulation of Y705-STAT3 phosphorylation and Vps34 protein levels was prevented in skeletal muscle of Fyn null mice. |
| 1809 | 22745922 | These data demonstrate a Fyn/STAT3/Vps34 pathway that is responsible for fiber-type-specific regulation of macroautophagy and skeletal muscle atrophy. |
| 1810 | 22745922 | Mouse skeletal muscle fiber-type-specific macroautophagy and muscle wasting are regulated by a Fyn/STAT3/Vps34 signaling pathway. |
| 1811 | 22745922 | This was due to inhibition of macroautophagy via an mTORC1-independent but STAT3-dependent reduction in Vps34 protein levels and decreased Vps34/p150/Beclin1/Atg14 complex 1. |
| 1812 | 22745922 | In parallel, Y705-STAT3 phosphorylation increased with decreased Vps34 protein levels. |
| 1813 | 22745922 | Moreover, fed/starved regulation of Y705-STAT3 phosphorylation and Vps34 protein levels was prevented in skeletal muscle of Fyn null mice. |
| 1814 | 22745922 | These data demonstrate a Fyn/STAT3/Vps34 pathway that is responsible for fiber-type-specific regulation of macroautophagy and skeletal muscle atrophy. |
| 1815 | 22745922 | Mouse skeletal muscle fiber-type-specific macroautophagy and muscle wasting are regulated by a Fyn/STAT3/Vps34 signaling pathway. |
| 1816 | 22745922 | This was due to inhibition of macroautophagy via an mTORC1-independent but STAT3-dependent reduction in Vps34 protein levels and decreased Vps34/p150/Beclin1/Atg14 complex 1. |
| 1817 | 22745922 | In parallel, Y705-STAT3 phosphorylation increased with decreased Vps34 protein levels. |
| 1818 | 22745922 | Moreover, fed/starved regulation of Y705-STAT3 phosphorylation and Vps34 protein levels was prevented in skeletal muscle of Fyn null mice. |
| 1819 | 22745922 | These data demonstrate a Fyn/STAT3/Vps34 pathway that is responsible for fiber-type-specific regulation of macroautophagy and skeletal muscle atrophy. |
| 1820 | 22745922 | Mouse skeletal muscle fiber-type-specific macroautophagy and muscle wasting are regulated by a Fyn/STAT3/Vps34 signaling pathway. |
| 1821 | 22745922 | This was due to inhibition of macroautophagy via an mTORC1-independent but STAT3-dependent reduction in Vps34 protein levels and decreased Vps34/p150/Beclin1/Atg14 complex 1. |
| 1822 | 22745922 | In parallel, Y705-STAT3 phosphorylation increased with decreased Vps34 protein levels. |
| 1823 | 22745922 | Moreover, fed/starved regulation of Y705-STAT3 phosphorylation and Vps34 protein levels was prevented in skeletal muscle of Fyn null mice. |
| 1824 | 22745922 | These data demonstrate a Fyn/STAT3/Vps34 pathway that is responsible for fiber-type-specific regulation of macroautophagy and skeletal muscle atrophy. |
| 1825 | 22761857 | Assessing downstream signaling, DM, but not Ob myocytes demonstrated a trend towards an increased protein phosphorylation of STAT3 in DM myocytes (P = 0.067) accompanied by a reduced SOCS3 protein induction (P<0.05), in response to IL-6 administration. |
| 1826 | 22792085 | Our results showed that fenofibrate inhibited transforming growth factor-β (TGF-β) and IL-6-induced differentiation of Th17 cells in vitro. |
| 1827 | 22792085 | Furthermore, our data showed that fenofibrate reduced IL-21 production and STAT3 activation, a critical signal in the Th17 differentiation. |
| 1828 | 22841542 | Further assessment of gene expression in a network of protein interactions related to innate immunity highlighted Stat3 as a potential transcriptional regulator of IL-1 signalling. |
| 1829 | 22841542 | Our results also highlight a potential role for Stat3 in linking IL-1 signalling to adipogenesis and IR. |
| 1830 | 22841542 | Further assessment of gene expression in a network of protein interactions related to innate immunity highlighted Stat3 as a potential transcriptional regulator of IL-1 signalling. |
| 1831 | 22841542 | Our results also highlight a potential role for Stat3 in linking IL-1 signalling to adipogenesis and IR. |
| 1832 | 22842565 | Glucagon-like peptide-1 (GLP-1) induces M2 polarization of human macrophages via STAT3 activation. |
| 1833 | 22842565 | GLP-1 is now used for the treatment of diabetes because of its beneficial role against insulin resistance. |
| 1834 | 22842565 | The GLP-1 receptor (GLP-1R) is expressed on many cell types, including macrophages, and GLP-1 suppresses the development of atherosclerosis by inhibiting macrophage function. |
| 1835 | 22842565 | However, there have so far been few studies that have investigated the significance of GLP-1/GLP-1R signaling in macrophage activation. |
| 1836 | 22842565 | In the present study, we examined the effect of GLP-1 and exenatide, a GLP-1R agonist, on human monocyte-derived macrophage (HMDM) activation. |
| 1837 | 22842565 | We found that GLP-1 induced signal transducer and activator of transcription 3 (STAT3) activation. |
| 1838 | 22842565 | Silencing of GLP-1R suppressed the GLP-1-induced STAT3 activation. |
| 1839 | 22842565 | In addition, alternatively activated (M2) macrophage-related molecules, such as IL-10, CD163, and CD204 in HMDM, were significantly upregulated by GLP-1. |
| 1840 | 22842565 | Glucagon-like peptide-1 (GLP-1) induces M2 polarization of human macrophages via STAT3 activation. |
| 1841 | 22842565 | GLP-1 is now used for the treatment of diabetes because of its beneficial role against insulin resistance. |
| 1842 | 22842565 | The GLP-1 receptor (GLP-1R) is expressed on many cell types, including macrophages, and GLP-1 suppresses the development of atherosclerosis by inhibiting macrophage function. |
| 1843 | 22842565 | However, there have so far been few studies that have investigated the significance of GLP-1/GLP-1R signaling in macrophage activation. |
| 1844 | 22842565 | In the present study, we examined the effect of GLP-1 and exenatide, a GLP-1R agonist, on human monocyte-derived macrophage (HMDM) activation. |
| 1845 | 22842565 | We found that GLP-1 induced signal transducer and activator of transcription 3 (STAT3) activation. |
| 1846 | 22842565 | Silencing of GLP-1R suppressed the GLP-1-induced STAT3 activation. |
| 1847 | 22842565 | In addition, alternatively activated (M2) macrophage-related molecules, such as IL-10, CD163, and CD204 in HMDM, were significantly upregulated by GLP-1. |
| 1848 | 22842565 | Glucagon-like peptide-1 (GLP-1) induces M2 polarization of human macrophages via STAT3 activation. |
| 1849 | 22842565 | GLP-1 is now used for the treatment of diabetes because of its beneficial role against insulin resistance. |
| 1850 | 22842565 | The GLP-1 receptor (GLP-1R) is expressed on many cell types, including macrophages, and GLP-1 suppresses the development of atherosclerosis by inhibiting macrophage function. |
| 1851 | 22842565 | However, there have so far been few studies that have investigated the significance of GLP-1/GLP-1R signaling in macrophage activation. |
| 1852 | 22842565 | In the present study, we examined the effect of GLP-1 and exenatide, a GLP-1R agonist, on human monocyte-derived macrophage (HMDM) activation. |
| 1853 | 22842565 | We found that GLP-1 induced signal transducer and activator of transcription 3 (STAT3) activation. |
| 1854 | 22842565 | Silencing of GLP-1R suppressed the GLP-1-induced STAT3 activation. |
| 1855 | 22842565 | In addition, alternatively activated (M2) macrophage-related molecules, such as IL-10, CD163, and CD204 in HMDM, were significantly upregulated by GLP-1. |
| 1856 | 22915469 | Consistently, high-glucose (HG) treated rMC-1 cells, a Müller cell line, also showed upregulation of acetylated histones, accompanied with the overexpression of GFAP, p-STAT3, and NFκB-p65, and two inflammatory genes, TNFα and MCP-1. |
| 1857 | 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. |
| 1858 | 22941110 | Leptin promoted the physical interaction of JAK2 and ROCK1, thereby increasing phosphorylation of JAK2 and downstream activation of Stat3 and FOXO1. |
| 1859 | 22941110 | Mice lacking ROCK1 in either pro-opiomelanocortin (POMC) or agouti-related protein neurons, mediators of leptin action, displayed obesity and impaired leptin sensitivity. |
| 1860 | 22941110 | Notably, ROCK1 was a specific mediator of leptin, but not insulin, regulation of POMC neuronal activity. |
| 1861 | 22985931 | Quantitative proteomics reveals novel functions of osteoclast-associated receptor in STAT signaling and cell adhesion in human endothelial cells. |
| 1862 | 22985931 | Interestingly, OSCAR modulation reciprocally regulated signal transducer and activator of transcription 1 (STAT1) and 3 (STAT3). |
| 1863 | 22985931 | Thus, STAT1 and several interferon-induced proteins showed a clear inverse correlation to OSCAR expression, which was further verified by Western blot analysis. |
| 1864 | 22985931 | In contrast, it was found that OSCAR overexpression activated STAT3. |
| 1865 | 22985931 | In conclusion, using a comprehensive proteomic approach, endothelial cell-derived OSCAR was found to be involved in the STAT signaling pathway and to affect monocyte adhesion. |
| 1866 | 22985931 | Quantitative proteomics reveals novel functions of osteoclast-associated receptor in STAT signaling and cell adhesion in human endothelial cells. |
| 1867 | 22985931 | Interestingly, OSCAR modulation reciprocally regulated signal transducer and activator of transcription 1 (STAT1) and 3 (STAT3). |
| 1868 | 22985931 | Thus, STAT1 and several interferon-induced proteins showed a clear inverse correlation to OSCAR expression, which was further verified by Western blot analysis. |
| 1869 | 22985931 | In contrast, it was found that OSCAR overexpression activated STAT3. |
| 1870 | 22985931 | In conclusion, using a comprehensive proteomic approach, endothelial cell-derived OSCAR was found to be involved in the STAT signaling pathway and to affect monocyte adhesion. |
| 1871 | 23043161 | Constitutive STAT3 phosphorylation contributes to skeletal muscle insulin resistance in type 2 diabetes. |
| 1872 | 23043161 | Signal transducer and activator of transcription 3 (STAT3) is involved in cytokine- and nutrient-induced insulin resistance. |
| 1873 | 23043161 | The role of STAT3 in the development of skeletal muscle insulin resistance and type 2 diabetes (T2D) pathogenesis is incompletely defined. |
| 1874 | 23043161 | We tested the hypothesis that STAT3 signaling contributes to skeletal muscle insulin resistance in T2D. |
| 1875 | 23043161 | The direct role of STAT3 in the development of lipid-induced skeletal muscle insulin resistance was determined using small interfering (si)RNA. |
| 1876 | 23043161 | Phosphorylated STAT3, phosphorylated Janus kinase 2 (JAK2), and suppressor of cytokine signaling 3 (SOCS3) protein abundance was increased in skeletal muscle from T2D patients. |
| 1877 | 23043161 | STAT3 phosphorylation positively correlated with free fatty acid level and measures of insulin sensitivity in NGT but not T2D patients. |
| 1878 | 23043161 | Palmitate exposure led to a constitutive phosphorylation of STAT3, increased protein abundance of SOCS3, and development of insulin resistance in L6 myotubes. |
| 1879 | 23043161 | STAT3 gene silencing prevents lipid-induced insulin resistance in cultured myotubes. |
| 1880 | 23043161 | Collectively, our results implicate excessive STAT3 signaling in the development of skeletal muscle insulin resistance in T2D. |
| 1881 | 23043161 | Constitutive STAT3 phosphorylation contributes to skeletal muscle insulin resistance in type 2 diabetes. |
| 1882 | 23043161 | Signal transducer and activator of transcription 3 (STAT3) is involved in cytokine- and nutrient-induced insulin resistance. |
| 1883 | 23043161 | The role of STAT3 in the development of skeletal muscle insulin resistance and type 2 diabetes (T2D) pathogenesis is incompletely defined. |
| 1884 | 23043161 | We tested the hypothesis that STAT3 signaling contributes to skeletal muscle insulin resistance in T2D. |
| 1885 | 23043161 | The direct role of STAT3 in the development of lipid-induced skeletal muscle insulin resistance was determined using small interfering (si)RNA. |
| 1886 | 23043161 | Phosphorylated STAT3, phosphorylated Janus kinase 2 (JAK2), and suppressor of cytokine signaling 3 (SOCS3) protein abundance was increased in skeletal muscle from T2D patients. |
| 1887 | 23043161 | STAT3 phosphorylation positively correlated with free fatty acid level and measures of insulin sensitivity in NGT but not T2D patients. |
| 1888 | 23043161 | Palmitate exposure led to a constitutive phosphorylation of STAT3, increased protein abundance of SOCS3, and development of insulin resistance in L6 myotubes. |
| 1889 | 23043161 | STAT3 gene silencing prevents lipid-induced insulin resistance in cultured myotubes. |
| 1890 | 23043161 | Collectively, our results implicate excessive STAT3 signaling in the development of skeletal muscle insulin resistance in T2D. |
| 1891 | 23043161 | Constitutive STAT3 phosphorylation contributes to skeletal muscle insulin resistance in type 2 diabetes. |
| 1892 | 23043161 | Signal transducer and activator of transcription 3 (STAT3) is involved in cytokine- and nutrient-induced insulin resistance. |
| 1893 | 23043161 | The role of STAT3 in the development of skeletal muscle insulin resistance and type 2 diabetes (T2D) pathogenesis is incompletely defined. |
| 1894 | 23043161 | We tested the hypothesis that STAT3 signaling contributes to skeletal muscle insulin resistance in T2D. |
| 1895 | 23043161 | The direct role of STAT3 in the development of lipid-induced skeletal muscle insulin resistance was determined using small interfering (si)RNA. |
| 1896 | 23043161 | Phosphorylated STAT3, phosphorylated Janus kinase 2 (JAK2), and suppressor of cytokine signaling 3 (SOCS3) protein abundance was increased in skeletal muscle from T2D patients. |
| 1897 | 23043161 | STAT3 phosphorylation positively correlated with free fatty acid level and measures of insulin sensitivity in NGT but not T2D patients. |
| 1898 | 23043161 | Palmitate exposure led to a constitutive phosphorylation of STAT3, increased protein abundance of SOCS3, and development of insulin resistance in L6 myotubes. |
| 1899 | 23043161 | STAT3 gene silencing prevents lipid-induced insulin resistance in cultured myotubes. |
| 1900 | 23043161 | Collectively, our results implicate excessive STAT3 signaling in the development of skeletal muscle insulin resistance in T2D. |
| 1901 | 23043161 | Constitutive STAT3 phosphorylation contributes to skeletal muscle insulin resistance in type 2 diabetes. |
| 1902 | 23043161 | Signal transducer and activator of transcription 3 (STAT3) is involved in cytokine- and nutrient-induced insulin resistance. |
| 1903 | 23043161 | The role of STAT3 in the development of skeletal muscle insulin resistance and type 2 diabetes (T2D) pathogenesis is incompletely defined. |
| 1904 | 23043161 | We tested the hypothesis that STAT3 signaling contributes to skeletal muscle insulin resistance in T2D. |
| 1905 | 23043161 | The direct role of STAT3 in the development of lipid-induced skeletal muscle insulin resistance was determined using small interfering (si)RNA. |
| 1906 | 23043161 | Phosphorylated STAT3, phosphorylated Janus kinase 2 (JAK2), and suppressor of cytokine signaling 3 (SOCS3) protein abundance was increased in skeletal muscle from T2D patients. |
| 1907 | 23043161 | STAT3 phosphorylation positively correlated with free fatty acid level and measures of insulin sensitivity in NGT but not T2D patients. |
| 1908 | 23043161 | Palmitate exposure led to a constitutive phosphorylation of STAT3, increased protein abundance of SOCS3, and development of insulin resistance in L6 myotubes. |
| 1909 | 23043161 | STAT3 gene silencing prevents lipid-induced insulin resistance in cultured myotubes. |
| 1910 | 23043161 | Collectively, our results implicate excessive STAT3 signaling in the development of skeletal muscle insulin resistance in T2D. |
| 1911 | 23043161 | Constitutive STAT3 phosphorylation contributes to skeletal muscle insulin resistance in type 2 diabetes. |
| 1912 | 23043161 | Signal transducer and activator of transcription 3 (STAT3) is involved in cytokine- and nutrient-induced insulin resistance. |
| 1913 | 23043161 | The role of STAT3 in the development of skeletal muscle insulin resistance and type 2 diabetes (T2D) pathogenesis is incompletely defined. |
| 1914 | 23043161 | We tested the hypothesis that STAT3 signaling contributes to skeletal muscle insulin resistance in T2D. |
| 1915 | 23043161 | The direct role of STAT3 in the development of lipid-induced skeletal muscle insulin resistance was determined using small interfering (si)RNA. |
| 1916 | 23043161 | Phosphorylated STAT3, phosphorylated Janus kinase 2 (JAK2), and suppressor of cytokine signaling 3 (SOCS3) protein abundance was increased in skeletal muscle from T2D patients. |
| 1917 | 23043161 | STAT3 phosphorylation positively correlated with free fatty acid level and measures of insulin sensitivity in NGT but not T2D patients. |
| 1918 | 23043161 | Palmitate exposure led to a constitutive phosphorylation of STAT3, increased protein abundance of SOCS3, and development of insulin resistance in L6 myotubes. |
| 1919 | 23043161 | STAT3 gene silencing prevents lipid-induced insulin resistance in cultured myotubes. |
| 1920 | 23043161 | Collectively, our results implicate excessive STAT3 signaling in the development of skeletal muscle insulin resistance in T2D. |
| 1921 | 23043161 | Constitutive STAT3 phosphorylation contributes to skeletal muscle insulin resistance in type 2 diabetes. |
| 1922 | 23043161 | Signal transducer and activator of transcription 3 (STAT3) is involved in cytokine- and nutrient-induced insulin resistance. |
| 1923 | 23043161 | The role of STAT3 in the development of skeletal muscle insulin resistance and type 2 diabetes (T2D) pathogenesis is incompletely defined. |
| 1924 | 23043161 | We tested the hypothesis that STAT3 signaling contributes to skeletal muscle insulin resistance in T2D. |
| 1925 | 23043161 | The direct role of STAT3 in the development of lipid-induced skeletal muscle insulin resistance was determined using small interfering (si)RNA. |
| 1926 | 23043161 | Phosphorylated STAT3, phosphorylated Janus kinase 2 (JAK2), and suppressor of cytokine signaling 3 (SOCS3) protein abundance was increased in skeletal muscle from T2D patients. |
| 1927 | 23043161 | STAT3 phosphorylation positively correlated with free fatty acid level and measures of insulin sensitivity in NGT but not T2D patients. |
| 1928 | 23043161 | Palmitate exposure led to a constitutive phosphorylation of STAT3, increased protein abundance of SOCS3, and development of insulin resistance in L6 myotubes. |
| 1929 | 23043161 | STAT3 gene silencing prevents lipid-induced insulin resistance in cultured myotubes. |
| 1930 | 23043161 | Collectively, our results implicate excessive STAT3 signaling in the development of skeletal muscle insulin resistance in T2D. |
| 1931 | 23043161 | Constitutive STAT3 phosphorylation contributes to skeletal muscle insulin resistance in type 2 diabetes. |
| 1932 | 23043161 | Signal transducer and activator of transcription 3 (STAT3) is involved in cytokine- and nutrient-induced insulin resistance. |
| 1933 | 23043161 | The role of STAT3 in the development of skeletal muscle insulin resistance and type 2 diabetes (T2D) pathogenesis is incompletely defined. |
| 1934 | 23043161 | We tested the hypothesis that STAT3 signaling contributes to skeletal muscle insulin resistance in T2D. |
| 1935 | 23043161 | The direct role of STAT3 in the development of lipid-induced skeletal muscle insulin resistance was determined using small interfering (si)RNA. |
| 1936 | 23043161 | Phosphorylated STAT3, phosphorylated Janus kinase 2 (JAK2), and suppressor of cytokine signaling 3 (SOCS3) protein abundance was increased in skeletal muscle from T2D patients. |
| 1937 | 23043161 | STAT3 phosphorylation positively correlated with free fatty acid level and measures of insulin sensitivity in NGT but not T2D patients. |
| 1938 | 23043161 | Palmitate exposure led to a constitutive phosphorylation of STAT3, increased protein abundance of SOCS3, and development of insulin resistance in L6 myotubes. |
| 1939 | 23043161 | STAT3 gene silencing prevents lipid-induced insulin resistance in cultured myotubes. |
| 1940 | 23043161 | Collectively, our results implicate excessive STAT3 signaling in the development of skeletal muscle insulin resistance in T2D. |
| 1941 | 23043161 | Constitutive STAT3 phosphorylation contributes to skeletal muscle insulin resistance in type 2 diabetes. |
| 1942 | 23043161 | Signal transducer and activator of transcription 3 (STAT3) is involved in cytokine- and nutrient-induced insulin resistance. |
| 1943 | 23043161 | The role of STAT3 in the development of skeletal muscle insulin resistance and type 2 diabetes (T2D) pathogenesis is incompletely defined. |
| 1944 | 23043161 | We tested the hypothesis that STAT3 signaling contributes to skeletal muscle insulin resistance in T2D. |
| 1945 | 23043161 | The direct role of STAT3 in the development of lipid-induced skeletal muscle insulin resistance was determined using small interfering (si)RNA. |
| 1946 | 23043161 | Phosphorylated STAT3, phosphorylated Janus kinase 2 (JAK2), and suppressor of cytokine signaling 3 (SOCS3) protein abundance was increased in skeletal muscle from T2D patients. |
| 1947 | 23043161 | STAT3 phosphorylation positively correlated with free fatty acid level and measures of insulin sensitivity in NGT but not T2D patients. |
| 1948 | 23043161 | Palmitate exposure led to a constitutive phosphorylation of STAT3, increased protein abundance of SOCS3, and development of insulin resistance in L6 myotubes. |
| 1949 | 23043161 | STAT3 gene silencing prevents lipid-induced insulin resistance in cultured myotubes. |
| 1950 | 23043161 | Collectively, our results implicate excessive STAT3 signaling in the development of skeletal muscle insulin resistance in T2D. |
| 1951 | 23043161 | Constitutive STAT3 phosphorylation contributes to skeletal muscle insulin resistance in type 2 diabetes. |
| 1952 | 23043161 | Signal transducer and activator of transcription 3 (STAT3) is involved in cytokine- and nutrient-induced insulin resistance. |
| 1953 | 23043161 | The role of STAT3 in the development of skeletal muscle insulin resistance and type 2 diabetes (T2D) pathogenesis is incompletely defined. |
| 1954 | 23043161 | We tested the hypothesis that STAT3 signaling contributes to skeletal muscle insulin resistance in T2D. |
| 1955 | 23043161 | The direct role of STAT3 in the development of lipid-induced skeletal muscle insulin resistance was determined using small interfering (si)RNA. |
| 1956 | 23043161 | Phosphorylated STAT3, phosphorylated Janus kinase 2 (JAK2), and suppressor of cytokine signaling 3 (SOCS3) protein abundance was increased in skeletal muscle from T2D patients. |
| 1957 | 23043161 | STAT3 phosphorylation positively correlated with free fatty acid level and measures of insulin sensitivity in NGT but not T2D patients. |
| 1958 | 23043161 | Palmitate exposure led to a constitutive phosphorylation of STAT3, increased protein abundance of SOCS3, and development of insulin resistance in L6 myotubes. |
| 1959 | 23043161 | STAT3 gene silencing prevents lipid-induced insulin resistance in cultured myotubes. |
| 1960 | 23043161 | Collectively, our results implicate excessive STAT3 signaling in the development of skeletal muscle insulin resistance in T2D. |
| 1961 | 23043161 | Constitutive STAT3 phosphorylation contributes to skeletal muscle insulin resistance in type 2 diabetes. |
| 1962 | 23043161 | Signal transducer and activator of transcription 3 (STAT3) is involved in cytokine- and nutrient-induced insulin resistance. |
| 1963 | 23043161 | The role of STAT3 in the development of skeletal muscle insulin resistance and type 2 diabetes (T2D) pathogenesis is incompletely defined. |
| 1964 | 23043161 | We tested the hypothesis that STAT3 signaling contributes to skeletal muscle insulin resistance in T2D. |
| 1965 | 23043161 | The direct role of STAT3 in the development of lipid-induced skeletal muscle insulin resistance was determined using small interfering (si)RNA. |
| 1966 | 23043161 | Phosphorylated STAT3, phosphorylated Janus kinase 2 (JAK2), and suppressor of cytokine signaling 3 (SOCS3) protein abundance was increased in skeletal muscle from T2D patients. |
| 1967 | 23043161 | STAT3 phosphorylation positively correlated with free fatty acid level and measures of insulin sensitivity in NGT but not T2D patients. |
| 1968 | 23043161 | Palmitate exposure led to a constitutive phosphorylation of STAT3, increased protein abundance of SOCS3, and development of insulin resistance in L6 myotubes. |
| 1969 | 23043161 | STAT3 gene silencing prevents lipid-induced insulin resistance in cultured myotubes. |
| 1970 | 23043161 | Collectively, our results implicate excessive STAT3 signaling in the development of skeletal muscle insulin resistance in T2D. |
| 1971 | 23086036 | Interleukin-6 (IL-6) has a dual role in modulating insulin sensitivity, with evidence for this cytokine as both an enhancer and inhibitor of insulin action. |
| 1972 | 23086036 | Acute IL-6 exposure increased glycogen synthesis, glucose uptake, and signal transducer and activator of transcription 3 (STAT3) phosphorylation in cultured myotubes from normal glucose tolerant subjects. |
| 1973 | 23086036 | However, in type 2 diabetic patients, IL-6 was without effect on glucose metabolism and STAT3 signaling, concomitant with increased suppressor of cytokine signaling 3 (SOCS3) expression. |
| 1974 | 23086036 | Expression of IL-6, IL-6 receptor (IL-6R), or glycoprotein 130, as well as IL-6 secretion, was unaltered between cultured myotubes from normal glucose tolerant or type 2 diabetic subjects. |
| 1975 | 23086036 | Interleukin-6 (IL-6) has a dual role in modulating insulin sensitivity, with evidence for this cytokine as both an enhancer and inhibitor of insulin action. |
| 1976 | 23086036 | Acute IL-6 exposure increased glycogen synthesis, glucose uptake, and signal transducer and activator of transcription 3 (STAT3) phosphorylation in cultured myotubes from normal glucose tolerant subjects. |
| 1977 | 23086036 | However, in type 2 diabetic patients, IL-6 was without effect on glucose metabolism and STAT3 signaling, concomitant with increased suppressor of cytokine signaling 3 (SOCS3) expression. |
| 1978 | 23086036 | Expression of IL-6, IL-6 receptor (IL-6R), or glycoprotein 130, as well as IL-6 secretion, was unaltered between cultured myotubes from normal glucose tolerant or type 2 diabetic subjects. |
| 1979 | 23094067 | An immunofluorescence technique was used to determine the levels of oxidative DNA damage by anti-8-hydroxy-2-deoxyguanosine (8-OHdG) antibody, the protein expression of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and vascular endothelial growth factor (VEGF), in mice with CNV. |
| 1980 | 23094067 | Oxidative stress levels and the expression of p-STAT3 and VEGF were highly elevated both in mice and in cultured RPE cells. |
| 1981 | 23094067 | NAC also inhibited the overexpression of p-STAT3 and VEGF in CNV and in RPE cells. |
| 1982 | 23094067 | The JAK-2/STAT3 pathway inhibitor AG490 blocked VEGF expression but had no effect on the production of ROS in vitro. |
| 1983 | 23094067 | An immunofluorescence technique was used to determine the levels of oxidative DNA damage by anti-8-hydroxy-2-deoxyguanosine (8-OHdG) antibody, the protein expression of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and vascular endothelial growth factor (VEGF), in mice with CNV. |
| 1984 | 23094067 | Oxidative stress levels and the expression of p-STAT3 and VEGF were highly elevated both in mice and in cultured RPE cells. |
| 1985 | 23094067 | NAC also inhibited the overexpression of p-STAT3 and VEGF in CNV and in RPE cells. |
| 1986 | 23094067 | The JAK-2/STAT3 pathway inhibitor AG490 blocked VEGF expression but had no effect on the production of ROS in vitro. |
| 1987 | 23094067 | An immunofluorescence technique was used to determine the levels of oxidative DNA damage by anti-8-hydroxy-2-deoxyguanosine (8-OHdG) antibody, the protein expression of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and vascular endothelial growth factor (VEGF), in mice with CNV. |
| 1988 | 23094067 | Oxidative stress levels and the expression of p-STAT3 and VEGF were highly elevated both in mice and in cultured RPE cells. |
| 1989 | 23094067 | NAC also inhibited the overexpression of p-STAT3 and VEGF in CNV and in RPE cells. |
| 1990 | 23094067 | The JAK-2/STAT3 pathway inhibitor AG490 blocked VEGF expression but had no effect on the production of ROS in vitro. |
| 1991 | 23094067 | An immunofluorescence technique was used to determine the levels of oxidative DNA damage by anti-8-hydroxy-2-deoxyguanosine (8-OHdG) antibody, the protein expression of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and vascular endothelial growth factor (VEGF), in mice with CNV. |
| 1992 | 23094067 | Oxidative stress levels and the expression of p-STAT3 and VEGF were highly elevated both in mice and in cultured RPE cells. |
| 1993 | 23094067 | NAC also inhibited the overexpression of p-STAT3 and VEGF in CNV and in RPE cells. |
| 1994 | 23094067 | The JAK-2/STAT3 pathway inhibitor AG490 blocked VEGF expression but had no effect on the production of ROS in vitro. |
| 1995 | 23110196 | VAT comparison of these experimental groups revealed that type 2 diabetic-MO subjects exhibit the same pro-inflammatory profile than the high IR-MO patients, characterized by elevated levels of IL-1β, IL-6, TNFα, JNK1/2, ERK1/2, STAT3 and NFκB. |
| 1996 | 23143785 | Curcumin's pleiotropic activities emanate from its ability to modulate numerous signaling molecules such as pro-inflammatory cytokines, apoptotic proteins, NF-κB, cyclooxygenase-2, 5-LOX, STAT3, C-reactive protein, prostaglandin E(2), prostate-specific antigen, adhesion molecules, phosphorylase kinase, transforming growth factor-β, triglyceride, ET-1, creatinine, HO-1, AST, and ALT in human participants. |
| 1997 | 23162655 | The action of metformin was mediated through the upregulation of its main signaling molecule, the adenosine monophosphate-activated protein kinase (AMPK), as well as through the downregulation of the signal transducer and activator of transcription 3 (STAT3) and the Akt/PKB serine/threonine protein kinase. |
| 1998 | 23162655 | In leptin-treated cells, the drug reversed the effects of the cytokine on the AMPK and STAT3 pathways, but modulated Akt activity in a cell-dependent manner. |
| 1999 | 23162655 | Our results suggest that metformin or similar AMPK-targeting agents with optimized blood-brain-barrier penetrability could be developed as potential treatments of GBM and could be used in conjunction with other target drugs such as leptin receptor antagonists. |
| 2000 | 23162655 | The action of metformin was mediated through the upregulation of its main signaling molecule, the adenosine monophosphate-activated protein kinase (AMPK), as well as through the downregulation of the signal transducer and activator of transcription 3 (STAT3) and the Akt/PKB serine/threonine protein kinase. |
| 2001 | 23162655 | In leptin-treated cells, the drug reversed the effects of the cytokine on the AMPK and STAT3 pathways, but modulated Akt activity in a cell-dependent manner. |
| 2002 | 23162655 | Our results suggest that metformin or similar AMPK-targeting agents with optimized blood-brain-barrier penetrability could be developed as potential treatments of GBM and could be used in conjunction with other target drugs such as leptin receptor antagonists. |
| 2003 | 23170143 | Recent studies have shown that cerulein-activated nicotinamide adenine dinucleotide phosphate oxidase elicits reactive oxygen species, which trigger the phosphorylation of the JAK1, STAT1, and STAT3 proteins and induce the production of inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-1β, and IL-6, in pancreatic acinar cells. |
| 2004 | 23223021 | Amyloid-β induces hepatic insulin resistance in vivo via JAK2. |
| 2005 | 23223021 | Aβ can induce insulin resistance in cultured hepatocytes by activating the JAK2/STAT3/SOCS-1 signaling pathway. |
| 2006 | 23223021 | Amyloid precursor protein and presenilin 1 double-transgenic AD mouse models with increased circulating Aβ level show impaired glucose/insulin tolerance and hepatic insulin resistance. |
| 2007 | 23223021 | Injection of Aβ42 activates hepatic JAK2/STAT3/SOCS-1 signaling, and neutralization of Aβ in APPswe/PSEN1dE9 mice inhibits liver JAK2/STAT3/SOCS-1 signaling. |
| 2008 | 23223021 | Furthermore, knockdown of hepatic JAK2 by tail vein injection of adenovirus inhibits JAK2/STAT3/SOCS-1 signaling and improves glucose/insulin tolerance and hepatic insulin sensitivity in APPswe/PSEN1dE9 mice. |
| 2009 | 23223021 | Our results demonstrate that Aβ induces hepatic insulin resistance in vivo via JAK2, suggesting that inhibition of Aβ signaling is a new strategy toward resolving insulin resistance and T2DM. |
| 2010 | 23223021 | Amyloid-β induces hepatic insulin resistance in vivo via JAK2. |
| 2011 | 23223021 | Aβ can induce insulin resistance in cultured hepatocytes by activating the JAK2/STAT3/SOCS-1 signaling pathway. |
| 2012 | 23223021 | Amyloid precursor protein and presenilin 1 double-transgenic AD mouse models with increased circulating Aβ level show impaired glucose/insulin tolerance and hepatic insulin resistance. |
| 2013 | 23223021 | Injection of Aβ42 activates hepatic JAK2/STAT3/SOCS-1 signaling, and neutralization of Aβ in APPswe/PSEN1dE9 mice inhibits liver JAK2/STAT3/SOCS-1 signaling. |
| 2014 | 23223021 | Furthermore, knockdown of hepatic JAK2 by tail vein injection of adenovirus inhibits JAK2/STAT3/SOCS-1 signaling and improves glucose/insulin tolerance and hepatic insulin sensitivity in APPswe/PSEN1dE9 mice. |
| 2015 | 23223021 | Our results demonstrate that Aβ induces hepatic insulin resistance in vivo via JAK2, suggesting that inhibition of Aβ signaling is a new strategy toward resolving insulin resistance and T2DM. |
| 2016 | 23223021 | Amyloid-β induces hepatic insulin resistance in vivo via JAK2. |
| 2017 | 23223021 | Aβ can induce insulin resistance in cultured hepatocytes by activating the JAK2/STAT3/SOCS-1 signaling pathway. |
| 2018 | 23223021 | Amyloid precursor protein and presenilin 1 double-transgenic AD mouse models with increased circulating Aβ level show impaired glucose/insulin tolerance and hepatic insulin resistance. |
| 2019 | 23223021 | Injection of Aβ42 activates hepatic JAK2/STAT3/SOCS-1 signaling, and neutralization of Aβ in APPswe/PSEN1dE9 mice inhibits liver JAK2/STAT3/SOCS-1 signaling. |
| 2020 | 23223021 | Furthermore, knockdown of hepatic JAK2 by tail vein injection of adenovirus inhibits JAK2/STAT3/SOCS-1 signaling and improves glucose/insulin tolerance and hepatic insulin sensitivity in APPswe/PSEN1dE9 mice. |
| 2021 | 23223021 | Our results demonstrate that Aβ induces hepatic insulin resistance in vivo via JAK2, suggesting that inhibition of Aβ signaling is a new strategy toward resolving insulin resistance and T2DM. |
| 2022 | 23224631 | Amylin-induced downregulation of hippocampal neurogenesis is attenuated by leptin in a STAT3/AMPK/ERK-dependent manner in mice. |
| 2023 | 23251598 | Dose-dependent expression of hPLAP also led to marked activity of established pro-inflammatory IL-6/Stat3, TNFα, IKKβ and JNK signaling in lysates obtained from homogenized muscles. |
| 2024 | 23255598 | Hypoxia-inducible factor 1α regulates a SOCS3-STAT3-adiponectin signal transduction pathway in adipocytes. |
| 2025 | 23255598 | Hypoxia-inducible factor 1α (HIF1α) regulates pathways in energy metabolism that become dysregulated in obesity. |
| 2026 | 23255598 | Earlier studies revealed that HIF1α in adipose tissue is markedly elevated in high-fat diet-fed mice that are obese and insulin-resistant. |
| 2027 | 23255598 | Genetic ablation of HIF1α in adipose tissue decreased insulin resistance and obesity, accompanied by increased serum adiponectin levels. |
| 2028 | 23255598 | However, the exact mechanism whereby HIF1α regulates adiponectin remains unclear. |
| 2029 | 23255598 | Here, acriflavine (ACF), an inhibitor of HIF1α, induced the expression of adiponectin and reduced the expression of SOCS3 in cultured 3T3-L1 adipocytes. |
| 2030 | 23255598 | Mechanistic studies revealed that HIF1α suppressed the expression of adiponectin through a SOCS3-STAT3 pathway. |
| 2031 | 23255598 | Socs3 was identified as a novel HIF1α target gene based on chromatin immunoprecipitation and luciferase assays. |
| 2032 | 23255598 | STAT3 directly regulated adiponectin in vitro in cultured 3T3-L1 adipocytes. |
| 2033 | 23255598 | In vivo, ACF also regulated the SOCS3-STAT3-adiponectin pathway, and inhibition of HIF1α in adipose tissue was essential for ACF to improve the SOCS3-STAT3-adiponectin pathway to counteract insulin resistance. |
| 2034 | 23255598 | Hypoxia-inducible factor 1α regulates a SOCS3-STAT3-adiponectin signal transduction pathway in adipocytes. |
| 2035 | 23255598 | Hypoxia-inducible factor 1α (HIF1α) regulates pathways in energy metabolism that become dysregulated in obesity. |
| 2036 | 23255598 | Earlier studies revealed that HIF1α in adipose tissue is markedly elevated in high-fat diet-fed mice that are obese and insulin-resistant. |
| 2037 | 23255598 | Genetic ablation of HIF1α in adipose tissue decreased insulin resistance and obesity, accompanied by increased serum adiponectin levels. |
| 2038 | 23255598 | However, the exact mechanism whereby HIF1α regulates adiponectin remains unclear. |
| 2039 | 23255598 | Here, acriflavine (ACF), an inhibitor of HIF1α, induced the expression of adiponectin and reduced the expression of SOCS3 in cultured 3T3-L1 adipocytes. |
| 2040 | 23255598 | Mechanistic studies revealed that HIF1α suppressed the expression of adiponectin through a SOCS3-STAT3 pathway. |
| 2041 | 23255598 | Socs3 was identified as a novel HIF1α target gene based on chromatin immunoprecipitation and luciferase assays. |
| 2042 | 23255598 | STAT3 directly regulated adiponectin in vitro in cultured 3T3-L1 adipocytes. |
| 2043 | 23255598 | In vivo, ACF also regulated the SOCS3-STAT3-adiponectin pathway, and inhibition of HIF1α in adipose tissue was essential for ACF to improve the SOCS3-STAT3-adiponectin pathway to counteract insulin resistance. |
| 2044 | 23255598 | Hypoxia-inducible factor 1α regulates a SOCS3-STAT3-adiponectin signal transduction pathway in adipocytes. |
| 2045 | 23255598 | Hypoxia-inducible factor 1α (HIF1α) regulates pathways in energy metabolism that become dysregulated in obesity. |
| 2046 | 23255598 | Earlier studies revealed that HIF1α in adipose tissue is markedly elevated in high-fat diet-fed mice that are obese and insulin-resistant. |
| 2047 | 23255598 | Genetic ablation of HIF1α in adipose tissue decreased insulin resistance and obesity, accompanied by increased serum adiponectin levels. |
| 2048 | 23255598 | However, the exact mechanism whereby HIF1α regulates adiponectin remains unclear. |
| 2049 | 23255598 | Here, acriflavine (ACF), an inhibitor of HIF1α, induced the expression of adiponectin and reduced the expression of SOCS3 in cultured 3T3-L1 adipocytes. |
| 2050 | 23255598 | Mechanistic studies revealed that HIF1α suppressed the expression of adiponectin through a SOCS3-STAT3 pathway. |
| 2051 | 23255598 | Socs3 was identified as a novel HIF1α target gene based on chromatin immunoprecipitation and luciferase assays. |
| 2052 | 23255598 | STAT3 directly regulated adiponectin in vitro in cultured 3T3-L1 adipocytes. |
| 2053 | 23255598 | In vivo, ACF also regulated the SOCS3-STAT3-adiponectin pathway, and inhibition of HIF1α in adipose tissue was essential for ACF to improve the SOCS3-STAT3-adiponectin pathway to counteract insulin resistance. |
| 2054 | 23255598 | Hypoxia-inducible factor 1α regulates a SOCS3-STAT3-adiponectin signal transduction pathway in adipocytes. |
| 2055 | 23255598 | Hypoxia-inducible factor 1α (HIF1α) regulates pathways in energy metabolism that become dysregulated in obesity. |
| 2056 | 23255598 | Earlier studies revealed that HIF1α in adipose tissue is markedly elevated in high-fat diet-fed mice that are obese and insulin-resistant. |
| 2057 | 23255598 | Genetic ablation of HIF1α in adipose tissue decreased insulin resistance and obesity, accompanied by increased serum adiponectin levels. |
| 2058 | 23255598 | However, the exact mechanism whereby HIF1α regulates adiponectin remains unclear. |
| 2059 | 23255598 | Here, acriflavine (ACF), an inhibitor of HIF1α, induced the expression of adiponectin and reduced the expression of SOCS3 in cultured 3T3-L1 adipocytes. |
| 2060 | 23255598 | Mechanistic studies revealed that HIF1α suppressed the expression of adiponectin through a SOCS3-STAT3 pathway. |
| 2061 | 23255598 | Socs3 was identified as a novel HIF1α target gene based on chromatin immunoprecipitation and luciferase assays. |
| 2062 | 23255598 | STAT3 directly regulated adiponectin in vitro in cultured 3T3-L1 adipocytes. |
| 2063 | 23255598 | In vivo, ACF also regulated the SOCS3-STAT3-adiponectin pathway, and inhibition of HIF1α in adipose tissue was essential for ACF to improve the SOCS3-STAT3-adiponectin pathway to counteract insulin resistance. |
| 2064 | 23333931 | 25-Hydroxyvitamin D3 attenuates experimental periodontitis through downregulation of TLR4 and JAK1/STAT3 signaling in diabetic mice. |
| 2065 | 23333931 | Immunohistochemical staining and western blot analysis of gingival epithelia revealed that vitamin D receptor (VDR) expression was enhanced upon 25-OHD3 treatment, while toll-like receptor 4 (TLR4) expression was reduced. |
| 2066 | 23333931 | The expressions of Janus family kinase (JAK) 1 and signal transducer and activator of transcription (STAT) 3 as well as their phosphorylation were inhibited in gingival epithelia of diabetic periodontitis mice, whereas the expression and phosphorylation of STAT1 remained unchanged. |
| 2067 | 23333931 | These results suggest that 25-OHD3 could improve diabetic periodontitis through downregulation of TLR4 and JAK1/STAT3 signaling in the gingival epithelium. |
| 2068 | 23333931 | 25-Hydroxyvitamin D3 attenuates experimental periodontitis through downregulation of TLR4 and JAK1/STAT3 signaling in diabetic mice. |
| 2069 | 23333931 | Immunohistochemical staining and western blot analysis of gingival epithelia revealed that vitamin D receptor (VDR) expression was enhanced upon 25-OHD3 treatment, while toll-like receptor 4 (TLR4) expression was reduced. |
| 2070 | 23333931 | The expressions of Janus family kinase (JAK) 1 and signal transducer and activator of transcription (STAT) 3 as well as their phosphorylation were inhibited in gingival epithelia of diabetic periodontitis mice, whereas the expression and phosphorylation of STAT1 remained unchanged. |
| 2071 | 23333931 | These results suggest that 25-OHD3 could improve diabetic periodontitis through downregulation of TLR4 and JAK1/STAT3 signaling in the gingival epithelium. |
| 2072 | 23333931 | 25-Hydroxyvitamin D3 attenuates experimental periodontitis through downregulation of TLR4 and JAK1/STAT3 signaling in diabetic mice. |
| 2073 | 23333931 | Immunohistochemical staining and western blot analysis of gingival epithelia revealed that vitamin D receptor (VDR) expression was enhanced upon 25-OHD3 treatment, while toll-like receptor 4 (TLR4) expression was reduced. |
| 2074 | 23333931 | The expressions of Janus family kinase (JAK) 1 and signal transducer and activator of transcription (STAT) 3 as well as their phosphorylation were inhibited in gingival epithelia of diabetic periodontitis mice, whereas the expression and phosphorylation of STAT1 remained unchanged. |
| 2075 | 23333931 | These results suggest that 25-OHD3 could improve diabetic periodontitis through downregulation of TLR4 and JAK1/STAT3 signaling in the gingival epithelium. |
| 2076 | 23418498 | Our causal reasoning algorithm suggested the involvement of novel gene networks, such as NEUROG3/E2F1/KDM5B and SOCS3/STAT3/IL-6, in endocrine cell development We experimentally investigated the role of the top-ranked prediction by showing that addition of exogenous IL-6 could affect the expression of the endocrine progenitor genes NEUROG3 and NKX2.2. |
| 2077 | 23474485 | Hepatic STAT3 phosphorylation after histidine ICV administration was attenuated in histamine H1 receptor knockout (Hrh1KO) mice but not in neuron-specific insulin receptor knockout (NIRKO) mice. |
| 2078 | 23474485 | Conversely, hepatic STAT3 phosphorylation after insulin ICV administration was attenuated in NIRKO but not in Hrh1KO mice. |
| 2079 | 23474485 | Hepatic STAT3 phosphorylation after histidine ICV administration was attenuated in histamine H1 receptor knockout (Hrh1KO) mice but not in neuron-specific insulin receptor knockout (NIRKO) mice. |
| 2080 | 23474485 | Conversely, hepatic STAT3 phosphorylation after insulin ICV administration was attenuated in NIRKO but not in Hrh1KO mice. |
| 2081 | 23504315 | LIM-homeodomain transcription factor Isl-1 mediates the effect of leptin on insulin secretion in mice. |
| 2082 | 23504315 | In addition to the well known regulating effects of leptin on energy balance and glucose homeostasis through the central nervous system, circulating leptin has a direct effect on pancreatic islet and insulin secretion through its receptor (OBRb). |
| 2083 | 23504315 | The LIM-homeodomain transcription factor Isl-1 is expressed in all classes of pancreatic endocrine cells and is involved in regulating both islet development and insulin secretion. |
| 2084 | 23504315 | However, the interactions and physiological significance of leptin and Isl-1 in pancreatic islets remain to be established. |
| 2085 | 23504315 | Here, we show that most of leptin target cells in pancreatic islets and NIT beta cells express Isl-1. |
| 2086 | 23504315 | Both in vivo and in vitro results demonstrate that leptin suppresses Isl-1 expression and insulin secretion in islet in physiological and pathophysiological conditions, e.g. high fat diet. |
| 2087 | 23504315 | This effect of leptin on insulin secretion is lost in leptin receptor-defective db/db and Isl-1-inducible knock-out mice. |
| 2088 | 23504315 | We conclude that the action of leptin on insulin secretion is at least partly mediated by Isl-1. |
| 2089 | 23504315 | Another new finding of this study is that Isl-1 acts as a direct downstream target of leptin signaling molecule STAT3 to influence the effect of leptin on insulin secretion, whereas inversely, insulin has feedback regulating effects on Isl-1 expression through JAK-STAT3 pathway. |
| 2090 | 23510983 | Differential effects of interleukin-13 and interleukin-6 on Jak/STAT signaling and cell viability in pancreatic β-cells. |
| 2091 | 23510983 | Since enteroviral infection of islet cells may influence the development of diabetes in humans, we examined the actions of two cytokines, IL-13 and IL-6, whose expression are reported to be altered in β-cells during enteroviral infection. |
| 2092 | 23510983 | Human and rodent islet cells were shown to express receptors for both IL-13 and IL-6, and treatment with either cytokine resulted in the rapid phosphorylation of STAT3 and STAT6. |
| 2093 | 23510983 | However, while β-cells were protected against a range of cytotoxic insults during exposure to IL-13, treatment with IL-6 enhanced cytotoxicity and western blotting revealed that IL-13 induced one specific isoform of phospho-STAT6 preferentially. |
| 2094 | 23510983 | Upon incubation with both cytokines together, the isoform of STAT6 that was upregulated by IL-13 alone was again induced, and the effects of IL-6 on β-cell viability were attenuated. |
| 2095 | 23510983 | Overall, the results suggest that induction of specific isoforms of STAT family transcription factors may underlie the cytoprotective actions of IL-13, and they imply that selective targeting of specific STAT-mediated signaling components could provide a means to ameliorate the loss of β-cell viability in diabetes. |
| 2096 | 23526220 | Metformin enhances cisplatin cytotoxicity by suppressing signal transducer and activator of transcription-3 activity independently of the liver kinase B1-AMP-activated protein kinase pathway. |
| 2097 | 23526220 | Metformin has been used as first-line treatment in patients with type 2 diabetes, and is reported to reduce cancer risk and progression by activating the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) pathway. |
| 2098 | 23526220 | However, drug resistance often develops through several mechanisms during the treatment course, including one mechanism mediated by the activation of the IL-6/signal transducer and activator of transcription (STAT)-3 pathway, related to the generation of reactive oxygen species (ROS). |
| 2099 | 23526220 | LKB1-AMPK silencing by small, interfering RNA or mammalian target of rapamycin (mTOR) inhibition by rapamycin or pp242 did not alter the effect of metformin on STAT3 activity suppression, suggesting that metformin can modulate the STAT3 pathway through an LKB1-AMPK-independent and probably mTOR-independent mechanism. |
| 2100 | 23526220 | Both mechanisms contributed to the ability of metformin to suppress STAT3 activation in cancer cells, which resulted in the decreased secretion of vascular endothelial growth factor by cancer cells. |
| 2101 | 23526220 | This is the first study to demonstrate that metformin suppresses STAT3 activation via LKB1-AMPK-mTOR-independent but ROS-related and autocrine IL-6 production-related pathways. |
| 2102 | 23526220 | Metformin enhances cisplatin cytotoxicity by suppressing signal transducer and activator of transcription-3 activity independently of the liver kinase B1-AMP-activated protein kinase pathway. |
| 2103 | 23526220 | Metformin has been used as first-line treatment in patients with type 2 diabetes, and is reported to reduce cancer risk and progression by activating the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) pathway. |
| 2104 | 23526220 | However, drug resistance often develops through several mechanisms during the treatment course, including one mechanism mediated by the activation of the IL-6/signal transducer and activator of transcription (STAT)-3 pathway, related to the generation of reactive oxygen species (ROS). |
| 2105 | 23526220 | LKB1-AMPK silencing by small, interfering RNA or mammalian target of rapamycin (mTOR) inhibition by rapamycin or pp242 did not alter the effect of metformin on STAT3 activity suppression, suggesting that metformin can modulate the STAT3 pathway through an LKB1-AMPK-independent and probably mTOR-independent mechanism. |
| 2106 | 23526220 | Both mechanisms contributed to the ability of metformin to suppress STAT3 activation in cancer cells, which resulted in the decreased secretion of vascular endothelial growth factor by cancer cells. |
| 2107 | 23526220 | This is the first study to demonstrate that metformin suppresses STAT3 activation via LKB1-AMPK-mTOR-independent but ROS-related and autocrine IL-6 production-related pathways. |
| 2108 | 23526220 | Metformin enhances cisplatin cytotoxicity by suppressing signal transducer and activator of transcription-3 activity independently of the liver kinase B1-AMP-activated protein kinase pathway. |
| 2109 | 23526220 | Metformin has been used as first-line treatment in patients with type 2 diabetes, and is reported to reduce cancer risk and progression by activating the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) pathway. |
| 2110 | 23526220 | However, drug resistance often develops through several mechanisms during the treatment course, including one mechanism mediated by the activation of the IL-6/signal transducer and activator of transcription (STAT)-3 pathway, related to the generation of reactive oxygen species (ROS). |
| 2111 | 23526220 | LKB1-AMPK silencing by small, interfering RNA or mammalian target of rapamycin (mTOR) inhibition by rapamycin or pp242 did not alter the effect of metformin on STAT3 activity suppression, suggesting that metformin can modulate the STAT3 pathway through an LKB1-AMPK-independent and probably mTOR-independent mechanism. |
| 2112 | 23526220 | Both mechanisms contributed to the ability of metformin to suppress STAT3 activation in cancer cells, which resulted in the decreased secretion of vascular endothelial growth factor by cancer cells. |
| 2113 | 23526220 | This is the first study to demonstrate that metformin suppresses STAT3 activation via LKB1-AMPK-mTOR-independent but ROS-related and autocrine IL-6 production-related pathways. |
| 2114 | 23526220 | Metformin enhances cisplatin cytotoxicity by suppressing signal transducer and activator of transcription-3 activity independently of the liver kinase B1-AMP-activated protein kinase pathway. |
| 2115 | 23526220 | Metformin has been used as first-line treatment in patients with type 2 diabetes, and is reported to reduce cancer risk and progression by activating the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) pathway. |
| 2116 | 23526220 | However, drug resistance often develops through several mechanisms during the treatment course, including one mechanism mediated by the activation of the IL-6/signal transducer and activator of transcription (STAT)-3 pathway, related to the generation of reactive oxygen species (ROS). |
| 2117 | 23526220 | LKB1-AMPK silencing by small, interfering RNA or mammalian target of rapamycin (mTOR) inhibition by rapamycin or pp242 did not alter the effect of metformin on STAT3 activity suppression, suggesting that metformin can modulate the STAT3 pathway through an LKB1-AMPK-independent and probably mTOR-independent mechanism. |
| 2118 | 23526220 | Both mechanisms contributed to the ability of metformin to suppress STAT3 activation in cancer cells, which resulted in the decreased secretion of vascular endothelial growth factor by cancer cells. |
| 2119 | 23526220 | This is the first study to demonstrate that metformin suppresses STAT3 activation via LKB1-AMPK-mTOR-independent but ROS-related and autocrine IL-6 production-related pathways. |
| 2120 | 23526220 | Metformin enhances cisplatin cytotoxicity by suppressing signal transducer and activator of transcription-3 activity independently of the liver kinase B1-AMP-activated protein kinase pathway. |
| 2121 | 23526220 | Metformin has been used as first-line treatment in patients with type 2 diabetes, and is reported to reduce cancer risk and progression by activating the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) pathway. |
| 2122 | 23526220 | However, drug resistance often develops through several mechanisms during the treatment course, including one mechanism mediated by the activation of the IL-6/signal transducer and activator of transcription (STAT)-3 pathway, related to the generation of reactive oxygen species (ROS). |
| 2123 | 23526220 | LKB1-AMPK silencing by small, interfering RNA or mammalian target of rapamycin (mTOR) inhibition by rapamycin or pp242 did not alter the effect of metformin on STAT3 activity suppression, suggesting that metformin can modulate the STAT3 pathway through an LKB1-AMPK-independent and probably mTOR-independent mechanism. |
| 2124 | 23526220 | Both mechanisms contributed to the ability of metformin to suppress STAT3 activation in cancer cells, which resulted in the decreased secretion of vascular endothelial growth factor by cancer cells. |
| 2125 | 23526220 | This is the first study to demonstrate that metformin suppresses STAT3 activation via LKB1-AMPK-mTOR-independent but ROS-related and autocrine IL-6 production-related pathways. |
| 2126 | 23530005 | Extracellular signal-regulated kinase in the ventromedial hypothalamus mediates leptin-induced glucose uptake in red-type skeletal muscle. |
| 2127 | 23530005 | We now show that signaling by extracellular signal-regulated kinase (ERK) and its upstream kinase MEK in the ventromedial hypothalamus (VMH) mediates the leptin-induced increase in glucose utilization as well as its insulin sensitivity in the whole body and in red-type skeletal muscle of mice through activation of the melanocortin receptor (MCR) in the VMH. |
| 2128 | 23530005 | In contrast, activation of signal transducer and activator of transcription 3 (STAT3), but not the MEK-ERK pathway, in the VMH by leptin enhances the insulin-induced suppression of endogenous glucose production in an MCR-independent manner, with this effect of leptin occurring only in the presence of an increased plasma concentration of insulin. |
| 2129 | 23530005 | Given that leptin requires 6 h to increase muscle glucose uptake, the transient activation of the MEK-ERK pathway in the VMH by leptin may play a role in the induction of synaptic plasticity in the VMH, resulting in the enhancement of MCR signaling in the nucleus and leading to an increase in insulin sensitivity in red-type muscle. |
| 2130 | 23533248 | Their anticancer mechanisms of action, after binding to specific receptors on cancer cells, include targeting the rat sarcoma-bound GTP (RAS) (95% inhibition)-mitogen-activated protein kinase kinase 1/2 (MEK 1/2) (98% inhibition)-extracellular signal-related kinase 1/2 (ERK 1/2) (96% inhibition) cascade in cancer cells. |
| 2131 | 23533248 | They also inhibit MAPK9, i.e. c-Jun N-terminal kinase 2. |
| 2132 | 23533248 | They are dual inhibitors of vascular endothelial growth factor (VEGF) and its VEGFR2 receptor (up to 89%). |
| 2133 | 23533248 | One of the downstream targets of VEGF is β-catenin, which they reduce up to 88%. |
| 2134 | 23533248 | AKT, a serine/threonine protein kinase, is reduced up to 64% by the cardiac hormones. |
| 2135 | 23533248 | STAT3 is specifically decreased as they do not affect STAT1. |
| 2136 | 23533248 | There is a cross-talk between the RAS-MEK 1/2-ERK 1/2 kinase cascade, VEGF, β-catenin, WNT, JNK, and STAT pathways and each of these pathways is inhibited by the cardiac hormones. |
| 2137 | 23533474 | Quercetin Preserves β -Cell Mass and Function in Fructose-Induced Hyperinsulinemia through Modulating Pancreatic Akt/FoxO1 Activation. |
| 2138 | 23533474 | Quercetin was confirmed to reduce serum insulin and leptin levels and blockade islet hyperplasia in fructose-fed rats. |
| 2139 | 23533474 | It also prevented fructose-induced β -cell proliferation and insulin hypersecretion in INS-1 β -cells. |
| 2140 | 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. |
| 2141 | 23533474 | The elevated Akt phosphorylation in fructose-treated INS-1 β -cells was also restored by quercetin. |
| 2142 | 23533474 | Additionally, quercetin suppressed the expression of pancreatic and duodenal homeobox 1 (Pdx1) and insulin gene (Ins1 and Ins2) in vivo and in vitro. |
| 2143 | 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. |
| 2144 | 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. |
| 2145 | 23593036 | Functional IL6R 358Ala allele impairs classical IL-6 receptor signaling and influences risk of diverse inflammatory diseases. |
| 2146 | 23593036 | Although a common, non-synonymous variant in the IL-6 receptor gene (IL6R Asp358Ala; rs2228145 A>C) is associated with the risk of several common diseases, with the 358Ala allele conferring protection from coronary heart disease (CHD), rheumatoid arthritis (RA), atrial fibrillation (AF), abdominal aortic aneurysm (AAA), and increased susceptibility to asthma, the variant's effect on IL-6 signaling is not known. |
| 2147 | 23593036 | We demonstrate that, although 358Ala increases transcription of the soluble IL6R isoform (P = 8.3×10⁻²²) and not the membrane-bound isoform, 358Ala reduces surface expression of IL-6R on CD4+ T cells and monocytes (up to 28% reduction per allele; P≤5.6×10⁻²²). |
| 2148 | 23593036 | Importantly, reduced expression of membrane-bound IL-6R resulted in impaired IL-6 responsiveness, as measured by decreased phosphorylation of the transcription factors STAT3 and STAT1 following stimulation with IL-6 (P≤5.2×10⁻⁷). |
| 2149 | 23593036 | Our findings elucidate the regulation of IL-6 signaling by IL-6R, which is causally relevant to several complex diseases, identify mechanisms for new approaches to target the IL-6/IL-6R axis, and anticipate differences in treatment response to IL-6 therapies based on this common IL6R variant. |
| 2150 | 23634778 | Leptin, resistin and visfatin: the missing link between endocrine metabolic disorders and immunity. |
| 2151 | 23634778 | Additionally, adipose tissue-secreted hormones such as leptin, visfatin, resistin, apelin, omentin, sex steroids, and various growth factors are now regarded as a functional part of the endocrine system. |
| 2152 | 23634778 | In obese and diabetic conditions, leptin deficiency inhibited the Jak/Stat3/PI3K and insulin pathways. |
| 2153 | 23641065 | This kinase, which is part of two protein complexes termed mTOR complex 1 (mTORC1) and 2 (mTORC2), has a fundamental role in coordinating anabolic and catabolic processes in response to growth factors and nutrients. |
| 2154 | 23641065 | Here, we review the connections between mTORC1 and gene transcription by focusing on its impact in regulating the activation of specific transcription factors including including STAT3, SREBPs, PPARγ, PPARα, HIF1α, YY1–PGC1α and TFEB. |
| 2155 | 23707791 | Pharmacological activation of AMPK suppresses inflammatory response evoked by IL-6 signalling in mouse liver and in human hepatocytes. |
| 2156 | 23707791 | Interleukin-6 (IL-6) induces inflammatory signalling in liver, leading to impaired insulin action in hepatocytes. |
| 2157 | 23707791 | In this study, we demonstrate that pharmacological activation of AMP-activated protein kinase (AMPK) represses IL-6-stimulated expression of proinflammatory markers serum amyloid A (Saa) as well as suppressor of cytokine signalling 3 (Socs3) in mouse liver. |
| 2158 | 23707791 | Further studies using the human hepatocellular carcinoma cell line HepG2 suggest that AMPK inhibits IL-6 signalling by repressing IL-6-stimulated phosphorylation of several downstream components of the pathway such as Janus kinase 1 (JAK1), SH2-domain containing protein tyrosine phosphatase 2 (SHP2) and signal transducer and activator of transcription 3 (STAT3). |
| 2159 | 23707791 | In summary, inhibition of IL-6 signalling cascade in liver by the metabolic master switch of the body, AMPK, supports the role of this kinase as a crucial point of convergence of metabolic and inflammatory pathways in hepatocytes. |
| 2160 | 23747931 | N-Acetylcysteine and allopurinol up-regulated the Jak/STAT3 and PI3K/Akt pathways via adiponectin and attenuated myocardial postischemic injury in diabetes. |
| 2161 | 23747931 | We postulated that NAC and ALP attenuated diabetic MI/R injury by up-regulating phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and Janus kinase 2/signal transducer and activator of transcription-3 (JAK2/STAT3) pathways subsequent to adiponectin (APN) activation. |
| 2162 | 23747931 | D rats displayed larger infarct size accompanied by decreased phosphorylation of Akt, STAT3 and decreased cardiac nitric oxide (NO) and APN levels. |
| 2163 | 23747931 | NAC and ALP decreased MI/R injury in D rats, enhanced phosphorylation of Akt and STAT3, and increased NO and APN. |
| 2164 | 23747931 | High glucose and hypoxia/reoxygenation exposure induced cell death and Akt and STAT3 inactivation in cultured cardiomyocytes, which were prevented by NAC and ALP. |
| 2165 | 23747931 | The PI3K inhibitor wortmannin and Jak2 inhibitor AG490 abolished the protection of NAC and ALP. |
| 2166 | 23747931 | Similarly, APN restored posthypoxic Akt and STAT3 activation and decreased cell death in cardiomyocytes. |
| 2167 | 23747931 | Gene silencing with AdipoR2 siRNA or STAT3 siRNA but not AdipoR1 siRNA abolished the protection of NAC and ALP. |
| 2168 | 23747931 | In conclusion, NAC and ALP prevented diabetic MI/R injury through PI3K/Akt and Jak2/STAT3 and cardiac APN may serve as a mediator via AdipoR2 in this process. |
| 2169 | 23747931 | N-Acetylcysteine and allopurinol up-regulated the Jak/STAT3 and PI3K/Akt pathways via adiponectin and attenuated myocardial postischemic injury in diabetes. |
| 2170 | 23747931 | We postulated that NAC and ALP attenuated diabetic MI/R injury by up-regulating phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and Janus kinase 2/signal transducer and activator of transcription-3 (JAK2/STAT3) pathways subsequent to adiponectin (APN) activation. |
| 2171 | 23747931 | D rats displayed larger infarct size accompanied by decreased phosphorylation of Akt, STAT3 and decreased cardiac nitric oxide (NO) and APN levels. |
| 2172 | 23747931 | NAC and ALP decreased MI/R injury in D rats, enhanced phosphorylation of Akt and STAT3, and increased NO and APN. |
| 2173 | 23747931 | High glucose and hypoxia/reoxygenation exposure induced cell death and Akt and STAT3 inactivation in cultured cardiomyocytes, which were prevented by NAC and ALP. |
| 2174 | 23747931 | The PI3K inhibitor wortmannin and Jak2 inhibitor AG490 abolished the protection of NAC and ALP. |
| 2175 | 23747931 | Similarly, APN restored posthypoxic Akt and STAT3 activation and decreased cell death in cardiomyocytes. |
| 2176 | 23747931 | Gene silencing with AdipoR2 siRNA or STAT3 siRNA but not AdipoR1 siRNA abolished the protection of NAC and ALP. |
| 2177 | 23747931 | In conclusion, NAC and ALP prevented diabetic MI/R injury through PI3K/Akt and Jak2/STAT3 and cardiac APN may serve as a mediator via AdipoR2 in this process. |
| 2178 | 23747931 | N-Acetylcysteine and allopurinol up-regulated the Jak/STAT3 and PI3K/Akt pathways via adiponectin and attenuated myocardial postischemic injury in diabetes. |
| 2179 | 23747931 | We postulated that NAC and ALP attenuated diabetic MI/R injury by up-regulating phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and Janus kinase 2/signal transducer and activator of transcription-3 (JAK2/STAT3) pathways subsequent to adiponectin (APN) activation. |
| 2180 | 23747931 | D rats displayed larger infarct size accompanied by decreased phosphorylation of Akt, STAT3 and decreased cardiac nitric oxide (NO) and APN levels. |
| 2181 | 23747931 | NAC and ALP decreased MI/R injury in D rats, enhanced phosphorylation of Akt and STAT3, and increased NO and APN. |
| 2182 | 23747931 | High glucose and hypoxia/reoxygenation exposure induced cell death and Akt and STAT3 inactivation in cultured cardiomyocytes, which were prevented by NAC and ALP. |
| 2183 | 23747931 | The PI3K inhibitor wortmannin and Jak2 inhibitor AG490 abolished the protection of NAC and ALP. |
| 2184 | 23747931 | Similarly, APN restored posthypoxic Akt and STAT3 activation and decreased cell death in cardiomyocytes. |
| 2185 | 23747931 | Gene silencing with AdipoR2 siRNA or STAT3 siRNA but not AdipoR1 siRNA abolished the protection of NAC and ALP. |
| 2186 | 23747931 | In conclusion, NAC and ALP prevented diabetic MI/R injury through PI3K/Akt and Jak2/STAT3 and cardiac APN may serve as a mediator via AdipoR2 in this process. |
| 2187 | 23747931 | N-Acetylcysteine and allopurinol up-regulated the Jak/STAT3 and PI3K/Akt pathways via adiponectin and attenuated myocardial postischemic injury in diabetes. |
| 2188 | 23747931 | We postulated that NAC and ALP attenuated diabetic MI/R injury by up-regulating phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and Janus kinase 2/signal transducer and activator of transcription-3 (JAK2/STAT3) pathways subsequent to adiponectin (APN) activation. |
| 2189 | 23747931 | D rats displayed larger infarct size accompanied by decreased phosphorylation of Akt, STAT3 and decreased cardiac nitric oxide (NO) and APN levels. |
| 2190 | 23747931 | NAC and ALP decreased MI/R injury in D rats, enhanced phosphorylation of Akt and STAT3, and increased NO and APN. |
| 2191 | 23747931 | High glucose and hypoxia/reoxygenation exposure induced cell death and Akt and STAT3 inactivation in cultured cardiomyocytes, which were prevented by NAC and ALP. |
| 2192 | 23747931 | The PI3K inhibitor wortmannin and Jak2 inhibitor AG490 abolished the protection of NAC and ALP. |
| 2193 | 23747931 | Similarly, APN restored posthypoxic Akt and STAT3 activation and decreased cell death in cardiomyocytes. |
| 2194 | 23747931 | Gene silencing with AdipoR2 siRNA or STAT3 siRNA but not AdipoR1 siRNA abolished the protection of NAC and ALP. |
| 2195 | 23747931 | In conclusion, NAC and ALP prevented diabetic MI/R injury through PI3K/Akt and Jak2/STAT3 and cardiac APN may serve as a mediator via AdipoR2 in this process. |
| 2196 | 23747931 | N-Acetylcysteine and allopurinol up-regulated the Jak/STAT3 and PI3K/Akt pathways via adiponectin and attenuated myocardial postischemic injury in diabetes. |
| 2197 | 23747931 | We postulated that NAC and ALP attenuated diabetic MI/R injury by up-regulating phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and Janus kinase 2/signal transducer and activator of transcription-3 (JAK2/STAT3) pathways subsequent to adiponectin (APN) activation. |
| 2198 | 23747931 | D rats displayed larger infarct size accompanied by decreased phosphorylation of Akt, STAT3 and decreased cardiac nitric oxide (NO) and APN levels. |
| 2199 | 23747931 | NAC and ALP decreased MI/R injury in D rats, enhanced phosphorylation of Akt and STAT3, and increased NO and APN. |
| 2200 | 23747931 | High glucose and hypoxia/reoxygenation exposure induced cell death and Akt and STAT3 inactivation in cultured cardiomyocytes, which were prevented by NAC and ALP. |
| 2201 | 23747931 | The PI3K inhibitor wortmannin and Jak2 inhibitor AG490 abolished the protection of NAC and ALP. |
| 2202 | 23747931 | Similarly, APN restored posthypoxic Akt and STAT3 activation and decreased cell death in cardiomyocytes. |
| 2203 | 23747931 | Gene silencing with AdipoR2 siRNA or STAT3 siRNA but not AdipoR1 siRNA abolished the protection of NAC and ALP. |
| 2204 | 23747931 | In conclusion, NAC and ALP prevented diabetic MI/R injury through PI3K/Akt and Jak2/STAT3 and cardiac APN may serve as a mediator via AdipoR2 in this process. |
| 2205 | 23747931 | N-Acetylcysteine and allopurinol up-regulated the Jak/STAT3 and PI3K/Akt pathways via adiponectin and attenuated myocardial postischemic injury in diabetes. |
| 2206 | 23747931 | We postulated that NAC and ALP attenuated diabetic MI/R injury by up-regulating phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and Janus kinase 2/signal transducer and activator of transcription-3 (JAK2/STAT3) pathways subsequent to adiponectin (APN) activation. |
| 2207 | 23747931 | D rats displayed larger infarct size accompanied by decreased phosphorylation of Akt, STAT3 and decreased cardiac nitric oxide (NO) and APN levels. |
| 2208 | 23747931 | NAC and ALP decreased MI/R injury in D rats, enhanced phosphorylation of Akt and STAT3, and increased NO and APN. |
| 2209 | 23747931 | High glucose and hypoxia/reoxygenation exposure induced cell death and Akt and STAT3 inactivation in cultured cardiomyocytes, which were prevented by NAC and ALP. |
| 2210 | 23747931 | The PI3K inhibitor wortmannin and Jak2 inhibitor AG490 abolished the protection of NAC and ALP. |
| 2211 | 23747931 | Similarly, APN restored posthypoxic Akt and STAT3 activation and decreased cell death in cardiomyocytes. |
| 2212 | 23747931 | Gene silencing with AdipoR2 siRNA or STAT3 siRNA but not AdipoR1 siRNA abolished the protection of NAC and ALP. |
| 2213 | 23747931 | In conclusion, NAC and ALP prevented diabetic MI/R injury through PI3K/Akt and Jak2/STAT3 and cardiac APN may serve as a mediator via AdipoR2 in this process. |
| 2214 | 23747931 | N-Acetylcysteine and allopurinol up-regulated the Jak/STAT3 and PI3K/Akt pathways via adiponectin and attenuated myocardial postischemic injury in diabetes. |
| 2215 | 23747931 | We postulated that NAC and ALP attenuated diabetic MI/R injury by up-regulating phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and Janus kinase 2/signal transducer and activator of transcription-3 (JAK2/STAT3) pathways subsequent to adiponectin (APN) activation. |
| 2216 | 23747931 | D rats displayed larger infarct size accompanied by decreased phosphorylation of Akt, STAT3 and decreased cardiac nitric oxide (NO) and APN levels. |
| 2217 | 23747931 | NAC and ALP decreased MI/R injury in D rats, enhanced phosphorylation of Akt and STAT3, and increased NO and APN. |
| 2218 | 23747931 | High glucose and hypoxia/reoxygenation exposure induced cell death and Akt and STAT3 inactivation in cultured cardiomyocytes, which were prevented by NAC and ALP. |
| 2219 | 23747931 | The PI3K inhibitor wortmannin and Jak2 inhibitor AG490 abolished the protection of NAC and ALP. |
| 2220 | 23747931 | Similarly, APN restored posthypoxic Akt and STAT3 activation and decreased cell death in cardiomyocytes. |
| 2221 | 23747931 | Gene silencing with AdipoR2 siRNA or STAT3 siRNA but not AdipoR1 siRNA abolished the protection of NAC and ALP. |
| 2222 | 23747931 | In conclusion, NAC and ALP prevented diabetic MI/R injury through PI3K/Akt and Jak2/STAT3 and cardiac APN may serve as a mediator via AdipoR2 in this process. |
| 2223 | 23747931 | N-Acetylcysteine and allopurinol up-regulated the Jak/STAT3 and PI3K/Akt pathways via adiponectin and attenuated myocardial postischemic injury in diabetes. |
| 2224 | 23747931 | We postulated that NAC and ALP attenuated diabetic MI/R injury by up-regulating phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and Janus kinase 2/signal transducer and activator of transcription-3 (JAK2/STAT3) pathways subsequent to adiponectin (APN) activation. |
| 2225 | 23747931 | D rats displayed larger infarct size accompanied by decreased phosphorylation of Akt, STAT3 and decreased cardiac nitric oxide (NO) and APN levels. |
| 2226 | 23747931 | NAC and ALP decreased MI/R injury in D rats, enhanced phosphorylation of Akt and STAT3, and increased NO and APN. |
| 2227 | 23747931 | High glucose and hypoxia/reoxygenation exposure induced cell death and Akt and STAT3 inactivation in cultured cardiomyocytes, which were prevented by NAC and ALP. |
| 2228 | 23747931 | The PI3K inhibitor wortmannin and Jak2 inhibitor AG490 abolished the protection of NAC and ALP. |
| 2229 | 23747931 | Similarly, APN restored posthypoxic Akt and STAT3 activation and decreased cell death in cardiomyocytes. |
| 2230 | 23747931 | Gene silencing with AdipoR2 siRNA or STAT3 siRNA but not AdipoR1 siRNA abolished the protection of NAC and ALP. |
| 2231 | 23747931 | In conclusion, NAC and ALP prevented diabetic MI/R injury through PI3K/Akt and Jak2/STAT3 and cardiac APN may serve as a mediator via AdipoR2 in this process. |
| 2232 | 23751875 | Teasaponin treatment also reduced the protein levels of proinflammatory cytokines (TNF-α, IL-6, and/or IL-1β) and nuclear factor-κB signaling (phosphorylated inhibitory-κB kinase and phosphorylated inhibitory-κBα) in adipose tissue and the liver. |
| 2233 | 23751875 | Teasaponin treatment also enhanced the anorexigenic effect of central leptin administration, restored leptin phosphorylated signal transducer and activator of transcription-3 (p-STAT3) signaling in the arcuate nucleus, and increased hypothalamic expression of the anorexigenic peptide proopiomelanocortin. |
| 2234 | 23772809 | Validated targets for miR-223 that have effects on inflammation and infection include granzyme B, IKKα, Roquin and STAT3. |
| 2235 | 23772809 | With regard to cancer, validated targets include C/EBPβ, E2F1, FOXO1 and NFI-A. |
| 2236 | 23878227 | Regulation of adipose tissue T cell subsets by Stat3 is crucial for diet-induced obesity and insulin resistance. |
| 2237 | 23878227 | Here we show a crucial role for signal transducer and activator of transcription 3 (Stat3) in T cells in skewing adaptive immunity in visceral adipose tissue (VAT), thereby contributing to diet-induced obesity (DIO) and insulin resistance. |
| 2238 | 23878227 | Functional ablation of Stat3 in T cells reduces DIO, improves insulin sensitivity and glucose tolerance, and suppresses VAT inflammation. |
| 2239 | 23878227 | Importantly, Stat3 ablation reverses the high Th1/Treg ratio in VAT of DIO mice that is likely secondary to elevated IL-6 production, leading in turn to suppression of Tregs. |
| 2240 | 23878227 | Regulation of adipose tissue T cell subsets by Stat3 is crucial for diet-induced obesity and insulin resistance. |
| 2241 | 23878227 | Here we show a crucial role for signal transducer and activator of transcription 3 (Stat3) in T cells in skewing adaptive immunity in visceral adipose tissue (VAT), thereby contributing to diet-induced obesity (DIO) and insulin resistance. |
| 2242 | 23878227 | Functional ablation of Stat3 in T cells reduces DIO, improves insulin sensitivity and glucose tolerance, and suppresses VAT inflammation. |
| 2243 | 23878227 | Importantly, Stat3 ablation reverses the high Th1/Treg ratio in VAT of DIO mice that is likely secondary to elevated IL-6 production, leading in turn to suppression of Tregs. |
| 2244 | 23878227 | Regulation of adipose tissue T cell subsets by Stat3 is crucial for diet-induced obesity and insulin resistance. |
| 2245 | 23878227 | Here we show a crucial role for signal transducer and activator of transcription 3 (Stat3) in T cells in skewing adaptive immunity in visceral adipose tissue (VAT), thereby contributing to diet-induced obesity (DIO) and insulin resistance. |
| 2246 | 23878227 | Functional ablation of Stat3 in T cells reduces DIO, improves insulin sensitivity and glucose tolerance, and suppresses VAT inflammation. |
| 2247 | 23878227 | Importantly, Stat3 ablation reverses the high Th1/Treg ratio in VAT of DIO mice that is likely secondary to elevated IL-6 production, leading in turn to suppression of Tregs. |
| 2248 | 23878227 | Regulation of adipose tissue T cell subsets by Stat3 is crucial for diet-induced obesity and insulin resistance. |
| 2249 | 23878227 | Here we show a crucial role for signal transducer and activator of transcription 3 (Stat3) in T cells in skewing adaptive immunity in visceral adipose tissue (VAT), thereby contributing to diet-induced obesity (DIO) and insulin resistance. |
| 2250 | 23878227 | Functional ablation of Stat3 in T cells reduces DIO, improves insulin sensitivity and glucose tolerance, and suppresses VAT inflammation. |
| 2251 | 23878227 | Importantly, Stat3 ablation reverses the high Th1/Treg ratio in VAT of DIO mice that is likely secondary to elevated IL-6 production, leading in turn to suppression of Tregs. |
| 2252 | 23886751 | These proteins included prohibitin 1, protein disulphide isomerase A3, beta actin, profilin, aldo-ketoreductase 1 C2, alpha crystallin B and the annexins A1, A5 and A6. |
| 2253 | 23886751 | Differences in the abundances of several proteins were confirmed by immunoblotting: i.e., prohibitin 1, protein disulphide isomerase A3, beta actin, profilin and signal transducer and activator of transcription 3 proteins. |
| 2254 | 23935514 | The s908 mutation leads to a leucine to arginine substitution in the ectodomain of the hepatocyte growth factor (HGF) tyrosine kinase receptor, Met. |
| 2255 | 23935514 | Treatment with PI3K and STAT3 inhibitors, but not with MAPK inhibitors, phenocopies the donut pancreatic defect, further indicating that Met signals through migratory pathways during pancreas development. |
| 2256 | 23951017 | Here, we report that PTP1B deficiency ameliorates Dextran Sulfate Sodium (DSS)-induced murine experimental colitis via expanding CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSCs). |
| 2257 | 23951017 | Second, PTP1B levels in BM leukocytes were significantly decreased after cells were induced into MDSCs by IL-6 and GM-CSF, and the MDSC induction occurred more rapidly in PTP1B-null mice than in wild-type littermates, suggesting PTP1B as a negative regulator of MDSCs. |
| 2258 | 23951017 | Third, the adoptive transfer of MDSCs into mice with DSS-colitis significantly attenuated colitis, which accompanies with a decreased serum IL-17 level. |
| 2259 | 23951017 | Finally, PTP1B deficiency increased the frequency of MDSCs from BM cells likely through enhancing the activities of signal transducer and activator of transcription 3 (STAT3) and Janus kinase 2 (JAK2). |
| 2260 | 23967267 | Loss of the anorexic response to systemic 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside administration despite reducing hypothalamic AMP-activated protein kinase phosphorylation in insulin-deficient rats. |
| 2261 | 23967267 | This study tested whether chronic systemic administration of 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) could attenuate hyperphagia, reduce lean and fat mass losses, and improve whole-body energy homeostasis in insulin-deficient rats. |
| 2262 | 23967267 | Blood was collected for circulating leptin measurement and the hypothalami were extracted for the determination of suppressor of cytokine signaling 3 (SOCS3) content, as well as the content and phosphorylation of AMP-kinase (AMPK), acetyl-CoA carboxylase (ACC), and the signal transducer and activator of transcription 3 (STAT3). |
| 2263 | 23967267 | In non-diabetic rats, despite reducing adiposity, AICAR increased (∼1.7-fold) circulating leptin and reduced hypothalamic SOCS3 content and food intake by 67% and 25%, respectively. |
| 2264 | 23967267 | The anorexic effect of AICAR was lost in diabetic rats, even though hypothalamic AMPK and ACC phosphorylation markedly decreased in these animals. |
| 2265 | 23967267 | Importantly, hypothalamic SOCS3 and STAT3 levels remained elevated and reduced, respectively, after treatment of insulin-deficient rats with AICAR. |
| 2266 | 23967267 | Loss of the anorexic response to systemic 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside administration despite reducing hypothalamic AMP-activated protein kinase phosphorylation in insulin-deficient rats. |
| 2267 | 23967267 | This study tested whether chronic systemic administration of 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) could attenuate hyperphagia, reduce lean and fat mass losses, and improve whole-body energy homeostasis in insulin-deficient rats. |
| 2268 | 23967267 | Blood was collected for circulating leptin measurement and the hypothalami were extracted for the determination of suppressor of cytokine signaling 3 (SOCS3) content, as well as the content and phosphorylation of AMP-kinase (AMPK), acetyl-CoA carboxylase (ACC), and the signal transducer and activator of transcription 3 (STAT3). |
| 2269 | 23967267 | In non-diabetic rats, despite reducing adiposity, AICAR increased (∼1.7-fold) circulating leptin and reduced hypothalamic SOCS3 content and food intake by 67% and 25%, respectively. |
| 2270 | 23967267 | The anorexic effect of AICAR was lost in diabetic rats, even though hypothalamic AMPK and ACC phosphorylation markedly decreased in these animals. |
| 2271 | 23967267 | Importantly, hypothalamic SOCS3 and STAT3 levels remained elevated and reduced, respectively, after treatment of insulin-deficient rats with AICAR. |
| 2272 | 23975026 | Thioredoxin-interacting protein regulates insulin transcription through microRNA-204. |
| 2273 | 23975026 | Here we show that TXNIP and diabetes induce beta-cell expression of a specific microRNA, miR-204, which in turn blocks insulin production by directly targeting and downregulating MAFA, a known insulin transcription factor. |
| 2274 | 23975026 | In particular, we first discovered the regulation of miR-204 by TXNIP by microarray analysis, followed by validation studies in INS-1 beta cells, islets of Txnip-deficient mice, diabetic mouse models and primary human islets. |
| 2275 | 23975026 | We then further found that TXNIP induces miR-204 by inhibiting the activity of signal transducer and activator of transcription 3 (STAT3), a transcription factor that is involved in miR-204 regulation. |
| 2276 | 23975026 | We also identified MAFA as a target that is downregulated by miR-204. |
| 2277 | 23975026 | Taken together, our results demonstrate that TXNIP controls microRNA expression and insulin production and that miR-204 is involved in beta-cell function. |
| 2278 | 23975026 | The newly identified TXNIP-miR-204-MAFA-insulin pathway may contribute to diabetes progression and provides new insight into TXNIP function and microRNA biology in health and disease. |
| 2279 | 24011072 | Stat3 activation links a C/EBPδ to myostatin pathway to stimulate loss of muscle mass. |
| 2280 | 24011072 | Using CCAAT/enhancer-binding protein δ (C/EBPδ) KO mice and C2C12 myotubes with knockdown of C/EBPδ or myostatin, we determined that p-Stat3 initiates muscle wasting via C/EBPδ, stimulating myostatin, a negative muscle growth regulator. |
| 2281 | 24011072 | We verified that p-Stat3, C/EBPδ, and myostatin were increased in muscles of CKD patients. |
| 2282 | 24011072 | The pathway from p-Stat3 to C/EBPδ to myostatin and muscle wasting could identify therapeutic targets that prevent muscle wasting. |
| 2283 | 24011072 | Stat3 activation links a C/EBPδ to myostatin pathway to stimulate loss of muscle mass. |
| 2284 | 24011072 | Using CCAAT/enhancer-binding protein δ (C/EBPδ) KO mice and C2C12 myotubes with knockdown of C/EBPδ or myostatin, we determined that p-Stat3 initiates muscle wasting via C/EBPδ, stimulating myostatin, a negative muscle growth regulator. |
| 2285 | 24011072 | We verified that p-Stat3, C/EBPδ, and myostatin were increased in muscles of CKD patients. |
| 2286 | 24011072 | The pathway from p-Stat3 to C/EBPδ to myostatin and muscle wasting could identify therapeutic targets that prevent muscle wasting. |
| 2287 | 24011072 | Stat3 activation links a C/EBPδ to myostatin pathway to stimulate loss of muscle mass. |
| 2288 | 24011072 | Using CCAAT/enhancer-binding protein δ (C/EBPδ) KO mice and C2C12 myotubes with knockdown of C/EBPδ or myostatin, we determined that p-Stat3 initiates muscle wasting via C/EBPδ, stimulating myostatin, a negative muscle growth regulator. |
| 2289 | 24011072 | We verified that p-Stat3, C/EBPδ, and myostatin were increased in muscles of CKD patients. |
| 2290 | 24011072 | The pathway from p-Stat3 to C/EBPδ to myostatin and muscle wasting could identify therapeutic targets that prevent muscle wasting. |
| 2291 | 24011072 | Stat3 activation links a C/EBPδ to myostatin pathway to stimulate loss of muscle mass. |
| 2292 | 24011072 | Using CCAAT/enhancer-binding protein δ (C/EBPδ) KO mice and C2C12 myotubes with knockdown of C/EBPδ or myostatin, we determined that p-Stat3 initiates muscle wasting via C/EBPδ, stimulating myostatin, a negative muscle growth regulator. |
| 2293 | 24011072 | We verified that p-Stat3, C/EBPδ, and myostatin were increased in muscles of CKD patients. |
| 2294 | 24011072 | The pathway from p-Stat3 to C/EBPδ to myostatin and muscle wasting could identify therapeutic targets that prevent muscle wasting. |