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Gene Information
Gene symbol: IGF1R
Gene name: insulin-like growth factor 1 receptor
HGNC ID: 5465
Synonyms: JTK13, CD221, IGFIR, MGC18216, IGFR
Related Genes
Related Sentences
| # | PMID | Sentence |
| 1 | 1310858 | Cloning and characterization of the human insulin-like growth factor-I receptor gene 5'-flanking region. |
| 2 | 1310858 | The insulin-like growth factor-I receptor (IGFIR) is a membrane-bound glycoprotein that mediates the action of insulin-like growth factors. |
| 3 | 1310858 | The promoter contained binding sites for the transcription factors Sp1, AP-2, and the epidermal growth factor receptor transcription factor (ETF). |
| 4 | 1310858 | Comparison of the IGFIR promoter with that of the human insulin receptor (IR) revealed structural similarities, although the arrangement of promoter elements differed. |
| 5 | 1310858 | Cloning and characterization of the human insulin-like growth factor-I receptor gene 5'-flanking region. |
| 6 | 1310858 | The insulin-like growth factor-I receptor (IGFIR) is a membrane-bound glycoprotein that mediates the action of insulin-like growth factors. |
| 7 | 1310858 | The promoter contained binding sites for the transcription factors Sp1, AP-2, and the epidermal growth factor receptor transcription factor (ETF). |
| 8 | 1310858 | Comparison of the IGFIR promoter with that of the human insulin receptor (IR) revealed structural similarities, although the arrangement of promoter elements differed. |
| 9 | 1316988 | Growth factor receptor regulation in the Minn-1 leprechaun: defects in both insulin receptor and epidermal growth factor receptor gene expression. |
| 10 | 1316988 | Using fibroblasts from the Minn-1 leprechaun, we have now investigated the expression of three different growth factor receptor genes: the IR, the insulin-like growth factor-I receptor (IGF-IR), and the epidermal growth factor receptor (EGFR). |
| 11 | 1316988 | In contrast to the IGF-IR, when the EGFR was studied, ligand binding and mRNA content were markedly decreased. |
| 12 | 1316988 | Growth factor receptor regulation in the Minn-1 leprechaun: defects in both insulin receptor and epidermal growth factor receptor gene expression. |
| 13 | 1316988 | Using fibroblasts from the Minn-1 leprechaun, we have now investigated the expression of three different growth factor receptor genes: the IR, the insulin-like growth factor-I receptor (IGF-IR), and the epidermal growth factor receptor (EGFR). |
| 14 | 1316988 | In contrast to the IGF-IR, when the EGFR was studied, ligand binding and mRNA content were markedly decreased. |
| 15 | 8001706 | Bioactivity must be similar to that of insulin without any enhancement of mitogenic properties due to an increase of the affinity for IGF1 receptor. |
| 16 | 8001706 | Lys B28-Pro B29 analogue is under clinical investigation to answer the following questions: does this analogue administered immediately before meal al decrease glycaemic excursions and the number of hypoglycemic episodes after meals compared to regular insulin administered 30 minutes before meal? |
| 17 | 8074208 | Expression of the genes for insulin-like growth factors and their receptors in bone during skeletal growth. |
| 18 | 8074208 | Insulin-like growth factors (IGF) are important regulators of skeletal growth. |
| 19 | 8074208 | To determine whether the capacity to produce and respond to these growth factors changes during skeletal development, we measured the protein and mRNA levels for IGF-I, IGF-II, and their receptors (IGF-IR and IGF-IIR, respectively) in the tibia and femur of rats before and up to 28 mo after birth. |
| 20 | 8074208 | This fall was most pronounced for IGF-II and IGF-IIR mRNA and least pronounced for IGF-I mRNA. |
| 21 | 8074208 | However, after 6 wk, both IGF-I and IGF-IR mRNA levels recovered toward the levels observed at birth. |
| 22 | 8074208 | In the prenatal bones, the signals for the mRNAs of IGF-II and IGF-IIR were stronger than the signals for the mRNAs of IGF-I and IGF-IR, although the content of IGF-I was three- to fivefold greater than that of IGF-II. |
| 23 | 8074208 | IGF-II levels fell postnatally, whereas the IGF-I content rose after birth such that the ratio IGF-I/IGF-II continued to increase with age. |
| 24 | 8074208 | Expression of the genes for insulin-like growth factors and their receptors in bone during skeletal growth. |
| 25 | 8074208 | Insulin-like growth factors (IGF) are important regulators of skeletal growth. |
| 26 | 8074208 | To determine whether the capacity to produce and respond to these growth factors changes during skeletal development, we measured the protein and mRNA levels for IGF-I, IGF-II, and their receptors (IGF-IR and IGF-IIR, respectively) in the tibia and femur of rats before and up to 28 mo after birth. |
| 27 | 8074208 | This fall was most pronounced for IGF-II and IGF-IIR mRNA and least pronounced for IGF-I mRNA. |
| 28 | 8074208 | However, after 6 wk, both IGF-I and IGF-IR mRNA levels recovered toward the levels observed at birth. |
| 29 | 8074208 | In the prenatal bones, the signals for the mRNAs of IGF-II and IGF-IIR were stronger than the signals for the mRNAs of IGF-I and IGF-IR, although the content of IGF-I was three- to fivefold greater than that of IGF-II. |
| 30 | 8074208 | IGF-II levels fell postnatally, whereas the IGF-I content rose after birth such that the ratio IGF-I/IGF-II continued to increase with age. |
| 31 | 8074208 | Expression of the genes for insulin-like growth factors and their receptors in bone during skeletal growth. |
| 32 | 8074208 | Insulin-like growth factors (IGF) are important regulators of skeletal growth. |
| 33 | 8074208 | To determine whether the capacity to produce and respond to these growth factors changes during skeletal development, we measured the protein and mRNA levels for IGF-I, IGF-II, and their receptors (IGF-IR and IGF-IIR, respectively) in the tibia and femur of rats before and up to 28 mo after birth. |
| 34 | 8074208 | This fall was most pronounced for IGF-II and IGF-IIR mRNA and least pronounced for IGF-I mRNA. |
| 35 | 8074208 | However, after 6 wk, both IGF-I and IGF-IR mRNA levels recovered toward the levels observed at birth. |
| 36 | 8074208 | In the prenatal bones, the signals for the mRNAs of IGF-II and IGF-IIR were stronger than the signals for the mRNAs of IGF-I and IGF-IR, although the content of IGF-I was three- to fivefold greater than that of IGF-II. |
| 37 | 8074208 | IGF-II levels fell postnatally, whereas the IGF-I content rose after birth such that the ratio IGF-I/IGF-II continued to increase with age. |
| 38 | 8104271 | Since relative or absolute insulin deficiency and insulin insensitivity are involved in the aetiology of non-insulin-dependent diabetes mellitus (NIDDM), we examined whether patients with NIDDM exhibit genetic variability in the coding region of insulin receptor substrate-1 (IRS-1), a candidate gene that is ubiquitous in insulin-sensitive and insulin-like growth factor 1 (IGF1) sensitive tissues, including those that determine glucose production and clearance and those with regulatory effects on pancreatic beta-cell function. |
| 39 | 8104271 | IRS-1 has a central role as an adaptor molecule that links the insulin-receptor and IGF1-receptor kinases with enzymes that regulate cellular metabolism and growth. |
| 40 | 8104271 | Both aminoacid substitutions were located close to tyrosine phosphorylation motifs that are putative recognition sites for insulin and IGF1 signal transmission proteins. |
| 41 | 8104271 | Analysis of the phenotypes showed that patients with NIDDM who had IRS-1 variants did not differ in their degree of insulin resistance compared with patients without known IRS-1 polymorphisms. |
| 42 | 8390684 | Increased expression of the insulin-like growth factor I receptor gene, IGF1R, in Wilms tumor is correlated with modulation of IGF1R promoter activity by the WT1 Wilms tumor gene product. |
| 43 | 8390684 | The expression of the gene encoding insulin-like growth factor II (IGF-II) is often elevated in these tumors. |
| 44 | 8390684 | Since many of the actions of IGF-II are mediated through activation of the IGF-I receptor (IGF-IR), we have measured the levels of IGF-IR mRNA in normal kidney and in Wilms tumor samples using solution hybridization/RNase protection assays. |
| 45 | 8390684 | IGF-IR gene (designated IGF1R) expression in the tumors was inversely correlated with the expression of the Wilms tumor suppressor gene WT1, whose inactivation appears to be a key step in the etiology of Wilms tumor. |
| 46 | 8390684 | Cotransfection of Chinese hamster ovary cells with rat and human IGF-IR gene promoter constructs driving luciferase reporter genes and with WT1 expression vectors showed that the active WT1 gene product represses IGF-IR promoter activity in a dose-dependent manner. |
| 47 | 8390684 | These results suggest that underexpression, deletion, or mutation of WT1 may result in increased expression of the IGF-IR, whose activation by IGF-II may be an important aspect of the biology of Wilms tumor. |
| 48 | 8390684 | Increased expression of the insulin-like growth factor I receptor gene, IGF1R, in Wilms tumor is correlated with modulation of IGF1R promoter activity by the WT1 Wilms tumor gene product. |
| 49 | 8390684 | The expression of the gene encoding insulin-like growth factor II (IGF-II) is often elevated in these tumors. |
| 50 | 8390684 | Since many of the actions of IGF-II are mediated through activation of the IGF-I receptor (IGF-IR), we have measured the levels of IGF-IR mRNA in normal kidney and in Wilms tumor samples using solution hybridization/RNase protection assays. |
| 51 | 8390684 | IGF-IR gene (designated IGF1R) expression in the tumors was inversely correlated with the expression of the Wilms tumor suppressor gene WT1, whose inactivation appears to be a key step in the etiology of Wilms tumor. |
| 52 | 8390684 | Cotransfection of Chinese hamster ovary cells with rat and human IGF-IR gene promoter constructs driving luciferase reporter genes and with WT1 expression vectors showed that the active WT1 gene product represses IGF-IR promoter activity in a dose-dependent manner. |
| 53 | 8390684 | These results suggest that underexpression, deletion, or mutation of WT1 may result in increased expression of the IGF-IR, whose activation by IGF-II may be an important aspect of the biology of Wilms tumor. |
| 54 | 8390684 | Increased expression of the insulin-like growth factor I receptor gene, IGF1R, in Wilms tumor is correlated with modulation of IGF1R promoter activity by the WT1 Wilms tumor gene product. |
| 55 | 8390684 | The expression of the gene encoding insulin-like growth factor II (IGF-II) is often elevated in these tumors. |
| 56 | 8390684 | Since many of the actions of IGF-II are mediated through activation of the IGF-I receptor (IGF-IR), we have measured the levels of IGF-IR mRNA in normal kidney and in Wilms tumor samples using solution hybridization/RNase protection assays. |
| 57 | 8390684 | IGF-IR gene (designated IGF1R) expression in the tumors was inversely correlated with the expression of the Wilms tumor suppressor gene WT1, whose inactivation appears to be a key step in the etiology of Wilms tumor. |
| 58 | 8390684 | Cotransfection of Chinese hamster ovary cells with rat and human IGF-IR gene promoter constructs driving luciferase reporter genes and with WT1 expression vectors showed that the active WT1 gene product represses IGF-IR promoter activity in a dose-dependent manner. |
| 59 | 8390684 | These results suggest that underexpression, deletion, or mutation of WT1 may result in increased expression of the IGF-IR, whose activation by IGF-II may be an important aspect of the biology of Wilms tumor. |
| 60 | 8390684 | Increased expression of the insulin-like growth factor I receptor gene, IGF1R, in Wilms tumor is correlated with modulation of IGF1R promoter activity by the WT1 Wilms tumor gene product. |
| 61 | 8390684 | The expression of the gene encoding insulin-like growth factor II (IGF-II) is often elevated in these tumors. |
| 62 | 8390684 | Since many of the actions of IGF-II are mediated through activation of the IGF-I receptor (IGF-IR), we have measured the levels of IGF-IR mRNA in normal kidney and in Wilms tumor samples using solution hybridization/RNase protection assays. |
| 63 | 8390684 | IGF-IR gene (designated IGF1R) expression in the tumors was inversely correlated with the expression of the Wilms tumor suppressor gene WT1, whose inactivation appears to be a key step in the etiology of Wilms tumor. |
| 64 | 8390684 | Cotransfection of Chinese hamster ovary cells with rat and human IGF-IR gene promoter constructs driving luciferase reporter genes and with WT1 expression vectors showed that the active WT1 gene product represses IGF-IR promoter activity in a dose-dependent manner. |
| 65 | 8390684 | These results suggest that underexpression, deletion, or mutation of WT1 may result in increased expression of the IGF-IR, whose activation by IGF-II may be an important aspect of the biology of Wilms tumor. |
| 66 | 8390684 | Increased expression of the insulin-like growth factor I receptor gene, IGF1R, in Wilms tumor is correlated with modulation of IGF1R promoter activity by the WT1 Wilms tumor gene product. |
| 67 | 8390684 | The expression of the gene encoding insulin-like growth factor II (IGF-II) is often elevated in these tumors. |
| 68 | 8390684 | Since many of the actions of IGF-II are mediated through activation of the IGF-I receptor (IGF-IR), we have measured the levels of IGF-IR mRNA in normal kidney and in Wilms tumor samples using solution hybridization/RNase protection assays. |
| 69 | 8390684 | IGF-IR gene (designated IGF1R) expression in the tumors was inversely correlated with the expression of the Wilms tumor suppressor gene WT1, whose inactivation appears to be a key step in the etiology of Wilms tumor. |
| 70 | 8390684 | Cotransfection of Chinese hamster ovary cells with rat and human IGF-IR gene promoter constructs driving luciferase reporter genes and with WT1 expression vectors showed that the active WT1 gene product represses IGF-IR promoter activity in a dose-dependent manner. |
| 71 | 8390684 | These results suggest that underexpression, deletion, or mutation of WT1 may result in increased expression of the IGF-IR, whose activation by IGF-II may be an important aspect of the biology of Wilms tumor. |
| 72 | 8454937 | Insulin and IGF1 receptor function among type II diabetic responders and nonresponders to glyburide. |
| 73 | 8454937 | This study evaluated the insulin and insulin-like growth factor-1 (IGF-1) receptor function among patients with type II diabetes who did or did not respond to 1 month of treatment with the oral sulfonylurea agent glyburide. |
| 74 | 8621530 | Interaction between the Grb10 SH2 domain and the insulin receptor carboxyl terminus. |
| 75 | 8621530 | We identified and isolated the Grb10 SH2 domain based on its interaction with the intracellular domain of the insulin receptor beta-subunit using the yeast two-hybrid system. |
| 76 | 8621530 | The interaction was specific for the insulin receptor and the insulin-like growth factor-1 receptor, and it required a catalytically active receptor kinase domain and an intact Grb10 SH2 domain. |
| 77 | 8621530 | Glutathione S-transferase fusion proteins containing the Grb10 SH2 domain associated in an insulin-dependent manner with insulin receptors from cell lysates and with purified insulin receptors. |
| 78 | 8621530 | Co-precipitation experiments revealed the association of cellular Grb10 with hormone-stimulated insulin receptors in cell extracts. |
| 79 | 8621530 | The Grb10 SH2 domain did not bind to an insulin receptor lacking 43 amino acids at the carboxyl terminus, and it exhibited highest affinity for a phosphopeptide containing Tyr(P)-1322. |
| 80 | 8621530 | Unlike p85 and Syp, which also bind to Tyr(P)-1322, Grb10 was not found to associate with insulin receptor substrate-1. |
| 81 | 8621530 | These results suggest that Grb10 is a novel insulin receptor interactive protein and provide direct evidence for an insulin receptor substrate-1-independent function of the insulin receptor carboxyl terminus in protein binding. |
| 82 | 8981937 | Insulin receptors (IR) and IGF-I receptors (IGF-IR) have been shown to form hybrid receptors in tissues coexpressing both molecules. |
| 83 | 8981937 | These results raise the possibility that alterations in expression of hybrid receptors may contribute to decreased insulin sensitivity, and to increased sensitivity to IGF-I. |
| 84 | 8981937 | Because IGF-I has been proposed as a hypoglycemic agent in NIDDM, these results are relevant to the development of new approaches to the treatment of insulin resistance of NIDDM. |
| 85 | 9030517 | Differential regulation of insulin-like growth factor-I (IGF-I) receptor gene expression by IGF-I and basic fibroblastic growth factor. |
| 86 | 9030517 | Insulin-like growth factor-I receptor (IGF-IR) gene expression is regulated by various stimuli, including hormones, growth factors, and nutritional status. |
| 87 | 9030517 | We have investigated the molecular mechanism by which two growth factors, insulin-like growth factor-I (IGF-I) and basic fibroblast growth factor (bFGF) regulate IGF-IR gene expression. bFGF increases the endogenous IGF-IR mRNA levels and IGF-IR promoter activity. |
| 88 | 9030517 | In contrast, IGF-I decreases the IGF-IR mRNA levels. |
| 89 | 9030517 | IGF-I down-regulates IGF-IR transcriptional activity as deduced from experiments in which the levels of pre-mRNA and mRNA were measured. |
| 90 | 9030517 | While these results strongly suggest an effect of IGF-I on IGF-IR transcriptional activity, no specific IGF-I response element was demonstrated in the 5'-untranslated region or 5'-flanking region studied. |
| 91 | 9030517 | Thus, bFGF and IGF-I have differential effects on IGF-IR gene transcription, with the IGF-I response region as yet unidentified. |
| 92 | 9030517 | Differential regulation of insulin-like growth factor-I (IGF-I) receptor gene expression by IGF-I and basic fibroblastic growth factor. |
| 93 | 9030517 | Insulin-like growth factor-I receptor (IGF-IR) gene expression is regulated by various stimuli, including hormones, growth factors, and nutritional status. |
| 94 | 9030517 | We have investigated the molecular mechanism by which two growth factors, insulin-like growth factor-I (IGF-I) and basic fibroblast growth factor (bFGF) regulate IGF-IR gene expression. bFGF increases the endogenous IGF-IR mRNA levels and IGF-IR promoter activity. |
| 95 | 9030517 | In contrast, IGF-I decreases the IGF-IR mRNA levels. |
| 96 | 9030517 | IGF-I down-regulates IGF-IR transcriptional activity as deduced from experiments in which the levels of pre-mRNA and mRNA were measured. |
| 97 | 9030517 | While these results strongly suggest an effect of IGF-I on IGF-IR transcriptional activity, no specific IGF-I response element was demonstrated in the 5'-untranslated region or 5'-flanking region studied. |
| 98 | 9030517 | Thus, bFGF and IGF-I have differential effects on IGF-IR gene transcription, with the IGF-I response region as yet unidentified. |
| 99 | 9030517 | Differential regulation of insulin-like growth factor-I (IGF-I) receptor gene expression by IGF-I and basic fibroblastic growth factor. |
| 100 | 9030517 | Insulin-like growth factor-I receptor (IGF-IR) gene expression is regulated by various stimuli, including hormones, growth factors, and nutritional status. |
| 101 | 9030517 | We have investigated the molecular mechanism by which two growth factors, insulin-like growth factor-I (IGF-I) and basic fibroblast growth factor (bFGF) regulate IGF-IR gene expression. bFGF increases the endogenous IGF-IR mRNA levels and IGF-IR promoter activity. |
| 102 | 9030517 | In contrast, IGF-I decreases the IGF-IR mRNA levels. |
| 103 | 9030517 | IGF-I down-regulates IGF-IR transcriptional activity as deduced from experiments in which the levels of pre-mRNA and mRNA were measured. |
| 104 | 9030517 | While these results strongly suggest an effect of IGF-I on IGF-IR transcriptional activity, no specific IGF-I response element was demonstrated in the 5'-untranslated region or 5'-flanking region studied. |
| 105 | 9030517 | Thus, bFGF and IGF-I have differential effects on IGF-IR gene transcription, with the IGF-I response region as yet unidentified. |
| 106 | 9030517 | Differential regulation of insulin-like growth factor-I (IGF-I) receptor gene expression by IGF-I and basic fibroblastic growth factor. |
| 107 | 9030517 | Insulin-like growth factor-I receptor (IGF-IR) gene expression is regulated by various stimuli, including hormones, growth factors, and nutritional status. |
| 108 | 9030517 | We have investigated the molecular mechanism by which two growth factors, insulin-like growth factor-I (IGF-I) and basic fibroblast growth factor (bFGF) regulate IGF-IR gene expression. bFGF increases the endogenous IGF-IR mRNA levels and IGF-IR promoter activity. |
| 109 | 9030517 | In contrast, IGF-I decreases the IGF-IR mRNA levels. |
| 110 | 9030517 | IGF-I down-regulates IGF-IR transcriptional activity as deduced from experiments in which the levels of pre-mRNA and mRNA were measured. |
| 111 | 9030517 | While these results strongly suggest an effect of IGF-I on IGF-IR transcriptional activity, no specific IGF-I response element was demonstrated in the 5'-untranslated region or 5'-flanking region studied. |
| 112 | 9030517 | Thus, bFGF and IGF-I have differential effects on IGF-IR gene transcription, with the IGF-I response region as yet unidentified. |
| 113 | 9030517 | Differential regulation of insulin-like growth factor-I (IGF-I) receptor gene expression by IGF-I and basic fibroblastic growth factor. |
| 114 | 9030517 | Insulin-like growth factor-I receptor (IGF-IR) gene expression is regulated by various stimuli, including hormones, growth factors, and nutritional status. |
| 115 | 9030517 | We have investigated the molecular mechanism by which two growth factors, insulin-like growth factor-I (IGF-I) and basic fibroblast growth factor (bFGF) regulate IGF-IR gene expression. bFGF increases the endogenous IGF-IR mRNA levels and IGF-IR promoter activity. |
| 116 | 9030517 | In contrast, IGF-I decreases the IGF-IR mRNA levels. |
| 117 | 9030517 | IGF-I down-regulates IGF-IR transcriptional activity as deduced from experiments in which the levels of pre-mRNA and mRNA were measured. |
| 118 | 9030517 | While these results strongly suggest an effect of IGF-I on IGF-IR transcriptional activity, no specific IGF-I response element was demonstrated in the 5'-untranslated region or 5'-flanking region studied. |
| 119 | 9030517 | Thus, bFGF and IGF-I have differential effects on IGF-IR gene transcription, with the IGF-I response region as yet unidentified. |
| 120 | 9030517 | Differential regulation of insulin-like growth factor-I (IGF-I) receptor gene expression by IGF-I and basic fibroblastic growth factor. |
| 121 | 9030517 | Insulin-like growth factor-I receptor (IGF-IR) gene expression is regulated by various stimuli, including hormones, growth factors, and nutritional status. |
| 122 | 9030517 | We have investigated the molecular mechanism by which two growth factors, insulin-like growth factor-I (IGF-I) and basic fibroblast growth factor (bFGF) regulate IGF-IR gene expression. bFGF increases the endogenous IGF-IR mRNA levels and IGF-IR promoter activity. |
| 123 | 9030517 | In contrast, IGF-I decreases the IGF-IR mRNA levels. |
| 124 | 9030517 | IGF-I down-regulates IGF-IR transcriptional activity as deduced from experiments in which the levels of pre-mRNA and mRNA were measured. |
| 125 | 9030517 | While these results strongly suggest an effect of IGF-I on IGF-IR transcriptional activity, no specific IGF-I response element was demonstrated in the 5'-untranslated region or 5'-flanking region studied. |
| 126 | 9030517 | Thus, bFGF and IGF-I have differential effects on IGF-IR gene transcription, with the IGF-I response region as yet unidentified. |
| 127 | 9061602 | The effects of IGF-I are mainly mediated through the IGF-I receptor (IGF-IR) and modulated by six specific IGF-binding proteins (IGFBPs). |
| 128 | 9061602 | We investigated the gene expression of IGF-I, IGF-IR and IGFBPs at a cellular level within the kidney using in situ hybridisation techniques in short-term (7 day) STZ-diabetic, insulin-treated euglycaemic and normal rats. |
| 129 | 9061602 | IGF-I, and IGFBP-4 and -5 mRNAs showed site-specific tubular changes whilst remaining unchanged in other parts of the kidney normally expressing the genes: IGF-I and IGFBP-4 mRNAs were reduced in TALs and proximal tubules respectively; IGFBP-5 mRNA was reduced in most distal tubular cells but strongly expressed in a few of these cells. |
| 130 | 9061602 | IGF-IR mRNA and the mRNAs for IGFBP-2, -3 and -6 were unchanged in STZ diabetes. |
| 131 | 9061602 | The effects of IGF-I are mainly mediated through the IGF-I receptor (IGF-IR) and modulated by six specific IGF-binding proteins (IGFBPs). |
| 132 | 9061602 | We investigated the gene expression of IGF-I, IGF-IR and IGFBPs at a cellular level within the kidney using in situ hybridisation techniques in short-term (7 day) STZ-diabetic, insulin-treated euglycaemic and normal rats. |
| 133 | 9061602 | IGF-I, and IGFBP-4 and -5 mRNAs showed site-specific tubular changes whilst remaining unchanged in other parts of the kidney normally expressing the genes: IGF-I and IGFBP-4 mRNAs were reduced in TALs and proximal tubules respectively; IGFBP-5 mRNA was reduced in most distal tubular cells but strongly expressed in a few of these cells. |
| 134 | 9061602 | IGF-IR mRNA and the mRNAs for IGFBP-2, -3 and -6 were unchanged in STZ diabetes. |
| 135 | 9061602 | The effects of IGF-I are mainly mediated through the IGF-I receptor (IGF-IR) and modulated by six specific IGF-binding proteins (IGFBPs). |
| 136 | 9061602 | We investigated the gene expression of IGF-I, IGF-IR and IGFBPs at a cellular level within the kidney using in situ hybridisation techniques in short-term (7 day) STZ-diabetic, insulin-treated euglycaemic and normal rats. |
| 137 | 9061602 | IGF-I, and IGFBP-4 and -5 mRNAs showed site-specific tubular changes whilst remaining unchanged in other parts of the kidney normally expressing the genes: IGF-I and IGFBP-4 mRNAs were reduced in TALs and proximal tubules respectively; IGFBP-5 mRNA was reduced in most distal tubular cells but strongly expressed in a few of these cells. |
| 138 | 9061602 | IGF-IR mRNA and the mRNAs for IGFBP-2, -3 and -6 were unchanged in STZ diabetes. |
| 139 | 9202243 | Tyrosine residues in the C-terminal domain of the insulin-like growth factor-I receptor mediate mitogenic and tumorigenic signals. |
| 140 | 9202243 | We investigated cellular proliferation, the transforming activity, and activation of known signal transduction pathways in NIH-3T3 cells stably expressing insulin-like growth factor-I receptors (IGF-IRs) with amino acid substitutions in the carboxy(C)-terminal domain. |
| 141 | 9202243 | The IsY clones lost the transforming ability of the wild type IGF-IR, whereas DBY clones formed colonies. |
| 142 | 9202243 | IGF-I-stimulated autophosphorylation of the IGF-IR and tyrosine phosphorylation of IRS-1 and SHC, known substrates in the IGF-IR signal transduction pathway, were studied. |
| 143 | 9202243 | Furthermore, the mutated IGF-IRs did not alter Grb2 association with phosphorylated IRS-1 and SHC. |
| 144 | 9202243 | IGF-I stimulation of Crk-II phosphorylation, a novel substrate of the IGF-IR, was similar in cells expressing mutated and wild-type IGF-IRs. |
| 145 | 9202243 | Tyrosine residues in the C-terminal domain of the insulin-like growth factor-I receptor mediate mitogenic and tumorigenic signals. |
| 146 | 9202243 | We investigated cellular proliferation, the transforming activity, and activation of known signal transduction pathways in NIH-3T3 cells stably expressing insulin-like growth factor-I receptors (IGF-IRs) with amino acid substitutions in the carboxy(C)-terminal domain. |
| 147 | 9202243 | The IsY clones lost the transforming ability of the wild type IGF-IR, whereas DBY clones formed colonies. |
| 148 | 9202243 | IGF-I-stimulated autophosphorylation of the IGF-IR and tyrosine phosphorylation of IRS-1 and SHC, known substrates in the IGF-IR signal transduction pathway, were studied. |
| 149 | 9202243 | Furthermore, the mutated IGF-IRs did not alter Grb2 association with phosphorylated IRS-1 and SHC. |
| 150 | 9202243 | IGF-I stimulation of Crk-II phosphorylation, a novel substrate of the IGF-IR, was similar in cells expressing mutated and wild-type IGF-IRs. |
| 151 | 9202243 | Tyrosine residues in the C-terminal domain of the insulin-like growth factor-I receptor mediate mitogenic and tumorigenic signals. |
| 152 | 9202243 | We investigated cellular proliferation, the transforming activity, and activation of known signal transduction pathways in NIH-3T3 cells stably expressing insulin-like growth factor-I receptors (IGF-IRs) with amino acid substitutions in the carboxy(C)-terminal domain. |
| 153 | 9202243 | The IsY clones lost the transforming ability of the wild type IGF-IR, whereas DBY clones formed colonies. |
| 154 | 9202243 | IGF-I-stimulated autophosphorylation of the IGF-IR and tyrosine phosphorylation of IRS-1 and SHC, known substrates in the IGF-IR signal transduction pathway, were studied. |
| 155 | 9202243 | Furthermore, the mutated IGF-IRs did not alter Grb2 association with phosphorylated IRS-1 and SHC. |
| 156 | 9202243 | IGF-I stimulation of Crk-II phosphorylation, a novel substrate of the IGF-IR, was similar in cells expressing mutated and wild-type IGF-IRs. |
| 157 | 9492043 | p53 regulates insulin-like growth factor-I (IGF-I) receptor expression and IGF-I-induced tyrosine phosphorylation in an osteosarcoma cell line: interaction between p53 and Sp1. |
| 158 | 9492043 | The insulin-like growth factor-I receptor (IGF-IR) is involved in tumorigenesis. |
| 159 | 9492043 | The aim of the present study was to investigate whether the IGF-IR is a physiological target for p53 in osteosarcoma cells. |
| 160 | 9492043 | The p53-induced regulation of IGF-IR levels was studied in a tetracycline-regulated expression system. |
| 161 | 9492043 | When expressed in Saos-2, osteosarcoma cells that lack p53, wild-type p53 decreased, whereas mutated p53 increased IGF-IR expression, and IGF-I-induced tyrosine phosphorylation of the IGF-IR. |
| 162 | 9492043 | Similarly, wild-type p53 decreased IGF-I-induced tyrosine phosphorylation of IRS-1. |
| 163 | 9492043 | A functional and physical interaction between p53 and Sp1, in the regulation of the IGF-R, was studied in osteosarcoma cells. |
| 164 | 9492043 | Expression of p53 decreased IGF-IR promoter activity, whereas no effect on promoter activity was seen by Sp1 expressed alone. |
| 165 | 9492043 | However, Sp1 counteracted the inhibitory effect of p53 on IGF-IR promoter activity in a dose-dependent manner. |
| 166 | 9492043 | Furthermore, wild-type and mutated p53 were coimmunoprecipitated with Sp1, indicating a physical interaction between p53 and Sp1. |
| 167 | 9492043 | In conclusion, p53 regulates IGF-IR expression, as reflected by a reduction in IGF-IR protein and a parallel reduction in IGF-I-induced tyrosine phosphorylation of the IGF-IR and IRS-1 in an osteosarcoma cell line. |
| 168 | 9492043 | These data indicate that the IGF-I receptor is a physiological target for p53 in osteosarcoma cells. |
| 169 | 9492043 | Furthermore, data supporting an interaction between p53 and Sp1 in the regulation of the promoter activity of IGF-IR are presented. |
| 170 | 9492043 | p53 regulates insulin-like growth factor-I (IGF-I) receptor expression and IGF-I-induced tyrosine phosphorylation in an osteosarcoma cell line: interaction between p53 and Sp1. |
| 171 | 9492043 | The insulin-like growth factor-I receptor (IGF-IR) is involved in tumorigenesis. |
| 172 | 9492043 | The aim of the present study was to investigate whether the IGF-IR is a physiological target for p53 in osteosarcoma cells. |
| 173 | 9492043 | The p53-induced regulation of IGF-IR levels was studied in a tetracycline-regulated expression system. |
| 174 | 9492043 | When expressed in Saos-2, osteosarcoma cells that lack p53, wild-type p53 decreased, whereas mutated p53 increased IGF-IR expression, and IGF-I-induced tyrosine phosphorylation of the IGF-IR. |
| 175 | 9492043 | Similarly, wild-type p53 decreased IGF-I-induced tyrosine phosphorylation of IRS-1. |
| 176 | 9492043 | A functional and physical interaction between p53 and Sp1, in the regulation of the IGF-R, was studied in osteosarcoma cells. |
| 177 | 9492043 | Expression of p53 decreased IGF-IR promoter activity, whereas no effect on promoter activity was seen by Sp1 expressed alone. |
| 178 | 9492043 | However, Sp1 counteracted the inhibitory effect of p53 on IGF-IR promoter activity in a dose-dependent manner. |
| 179 | 9492043 | Furthermore, wild-type and mutated p53 were coimmunoprecipitated with Sp1, indicating a physical interaction between p53 and Sp1. |
| 180 | 9492043 | In conclusion, p53 regulates IGF-IR expression, as reflected by a reduction in IGF-IR protein and a parallel reduction in IGF-I-induced tyrosine phosphorylation of the IGF-IR and IRS-1 in an osteosarcoma cell line. |
| 181 | 9492043 | These data indicate that the IGF-I receptor is a physiological target for p53 in osteosarcoma cells. |
| 182 | 9492043 | Furthermore, data supporting an interaction between p53 and Sp1 in the regulation of the promoter activity of IGF-IR are presented. |
| 183 | 9492043 | p53 regulates insulin-like growth factor-I (IGF-I) receptor expression and IGF-I-induced tyrosine phosphorylation in an osteosarcoma cell line: interaction between p53 and Sp1. |
| 184 | 9492043 | The insulin-like growth factor-I receptor (IGF-IR) is involved in tumorigenesis. |
| 185 | 9492043 | The aim of the present study was to investigate whether the IGF-IR is a physiological target for p53 in osteosarcoma cells. |
| 186 | 9492043 | The p53-induced regulation of IGF-IR levels was studied in a tetracycline-regulated expression system. |
| 187 | 9492043 | When expressed in Saos-2, osteosarcoma cells that lack p53, wild-type p53 decreased, whereas mutated p53 increased IGF-IR expression, and IGF-I-induced tyrosine phosphorylation of the IGF-IR. |
| 188 | 9492043 | Similarly, wild-type p53 decreased IGF-I-induced tyrosine phosphorylation of IRS-1. |
| 189 | 9492043 | A functional and physical interaction between p53 and Sp1, in the regulation of the IGF-R, was studied in osteosarcoma cells. |
| 190 | 9492043 | Expression of p53 decreased IGF-IR promoter activity, whereas no effect on promoter activity was seen by Sp1 expressed alone. |
| 191 | 9492043 | However, Sp1 counteracted the inhibitory effect of p53 on IGF-IR promoter activity in a dose-dependent manner. |
| 192 | 9492043 | Furthermore, wild-type and mutated p53 were coimmunoprecipitated with Sp1, indicating a physical interaction between p53 and Sp1. |
| 193 | 9492043 | In conclusion, p53 regulates IGF-IR expression, as reflected by a reduction in IGF-IR protein and a parallel reduction in IGF-I-induced tyrosine phosphorylation of the IGF-IR and IRS-1 in an osteosarcoma cell line. |
| 194 | 9492043 | These data indicate that the IGF-I receptor is a physiological target for p53 in osteosarcoma cells. |
| 195 | 9492043 | Furthermore, data supporting an interaction between p53 and Sp1 in the regulation of the promoter activity of IGF-IR are presented. |
| 196 | 9492043 | p53 regulates insulin-like growth factor-I (IGF-I) receptor expression and IGF-I-induced tyrosine phosphorylation in an osteosarcoma cell line: interaction between p53 and Sp1. |
| 197 | 9492043 | The insulin-like growth factor-I receptor (IGF-IR) is involved in tumorigenesis. |
| 198 | 9492043 | The aim of the present study was to investigate whether the IGF-IR is a physiological target for p53 in osteosarcoma cells. |
| 199 | 9492043 | The p53-induced regulation of IGF-IR levels was studied in a tetracycline-regulated expression system. |
| 200 | 9492043 | When expressed in Saos-2, osteosarcoma cells that lack p53, wild-type p53 decreased, whereas mutated p53 increased IGF-IR expression, and IGF-I-induced tyrosine phosphorylation of the IGF-IR. |
| 201 | 9492043 | Similarly, wild-type p53 decreased IGF-I-induced tyrosine phosphorylation of IRS-1. |
| 202 | 9492043 | A functional and physical interaction between p53 and Sp1, in the regulation of the IGF-R, was studied in osteosarcoma cells. |
| 203 | 9492043 | Expression of p53 decreased IGF-IR promoter activity, whereas no effect on promoter activity was seen by Sp1 expressed alone. |
| 204 | 9492043 | However, Sp1 counteracted the inhibitory effect of p53 on IGF-IR promoter activity in a dose-dependent manner. |
| 205 | 9492043 | Furthermore, wild-type and mutated p53 were coimmunoprecipitated with Sp1, indicating a physical interaction between p53 and Sp1. |
| 206 | 9492043 | In conclusion, p53 regulates IGF-IR expression, as reflected by a reduction in IGF-IR protein and a parallel reduction in IGF-I-induced tyrosine phosphorylation of the IGF-IR and IRS-1 in an osteosarcoma cell line. |
| 207 | 9492043 | These data indicate that the IGF-I receptor is a physiological target for p53 in osteosarcoma cells. |
| 208 | 9492043 | Furthermore, data supporting an interaction between p53 and Sp1 in the regulation of the promoter activity of IGF-IR are presented. |
| 209 | 9492043 | p53 regulates insulin-like growth factor-I (IGF-I) receptor expression and IGF-I-induced tyrosine phosphorylation in an osteosarcoma cell line: interaction between p53 and Sp1. |
| 210 | 9492043 | The insulin-like growth factor-I receptor (IGF-IR) is involved in tumorigenesis. |
| 211 | 9492043 | The aim of the present study was to investigate whether the IGF-IR is a physiological target for p53 in osteosarcoma cells. |
| 212 | 9492043 | The p53-induced regulation of IGF-IR levels was studied in a tetracycline-regulated expression system. |
| 213 | 9492043 | When expressed in Saos-2, osteosarcoma cells that lack p53, wild-type p53 decreased, whereas mutated p53 increased IGF-IR expression, and IGF-I-induced tyrosine phosphorylation of the IGF-IR. |
| 214 | 9492043 | Similarly, wild-type p53 decreased IGF-I-induced tyrosine phosphorylation of IRS-1. |
| 215 | 9492043 | A functional and physical interaction between p53 and Sp1, in the regulation of the IGF-R, was studied in osteosarcoma cells. |
| 216 | 9492043 | Expression of p53 decreased IGF-IR promoter activity, whereas no effect on promoter activity was seen by Sp1 expressed alone. |
| 217 | 9492043 | However, Sp1 counteracted the inhibitory effect of p53 on IGF-IR promoter activity in a dose-dependent manner. |
| 218 | 9492043 | Furthermore, wild-type and mutated p53 were coimmunoprecipitated with Sp1, indicating a physical interaction between p53 and Sp1. |
| 219 | 9492043 | In conclusion, p53 regulates IGF-IR expression, as reflected by a reduction in IGF-IR protein and a parallel reduction in IGF-I-induced tyrosine phosphorylation of the IGF-IR and IRS-1 in an osteosarcoma cell line. |
| 220 | 9492043 | These data indicate that the IGF-I receptor is a physiological target for p53 in osteosarcoma cells. |
| 221 | 9492043 | Furthermore, data supporting an interaction between p53 and Sp1 in the regulation of the promoter activity of IGF-IR are presented. |
| 222 | 9492043 | p53 regulates insulin-like growth factor-I (IGF-I) receptor expression and IGF-I-induced tyrosine phosphorylation in an osteosarcoma cell line: interaction between p53 and Sp1. |
| 223 | 9492043 | The insulin-like growth factor-I receptor (IGF-IR) is involved in tumorigenesis. |
| 224 | 9492043 | The aim of the present study was to investigate whether the IGF-IR is a physiological target for p53 in osteosarcoma cells. |
| 225 | 9492043 | The p53-induced regulation of IGF-IR levels was studied in a tetracycline-regulated expression system. |
| 226 | 9492043 | When expressed in Saos-2, osteosarcoma cells that lack p53, wild-type p53 decreased, whereas mutated p53 increased IGF-IR expression, and IGF-I-induced tyrosine phosphorylation of the IGF-IR. |
| 227 | 9492043 | Similarly, wild-type p53 decreased IGF-I-induced tyrosine phosphorylation of IRS-1. |
| 228 | 9492043 | A functional and physical interaction between p53 and Sp1, in the regulation of the IGF-R, was studied in osteosarcoma cells. |
| 229 | 9492043 | Expression of p53 decreased IGF-IR promoter activity, whereas no effect on promoter activity was seen by Sp1 expressed alone. |
| 230 | 9492043 | However, Sp1 counteracted the inhibitory effect of p53 on IGF-IR promoter activity in a dose-dependent manner. |
| 231 | 9492043 | Furthermore, wild-type and mutated p53 were coimmunoprecipitated with Sp1, indicating a physical interaction between p53 and Sp1. |
| 232 | 9492043 | In conclusion, p53 regulates IGF-IR expression, as reflected by a reduction in IGF-IR protein and a parallel reduction in IGF-I-induced tyrosine phosphorylation of the IGF-IR and IRS-1 in an osteosarcoma cell line. |
| 233 | 9492043 | These data indicate that the IGF-I receptor is a physiological target for p53 in osteosarcoma cells. |
| 234 | 9492043 | Furthermore, data supporting an interaction between p53 and Sp1 in the regulation of the promoter activity of IGF-IR are presented. |
| 235 | 9492043 | p53 regulates insulin-like growth factor-I (IGF-I) receptor expression and IGF-I-induced tyrosine phosphorylation in an osteosarcoma cell line: interaction between p53 and Sp1. |
| 236 | 9492043 | The insulin-like growth factor-I receptor (IGF-IR) is involved in tumorigenesis. |
| 237 | 9492043 | The aim of the present study was to investigate whether the IGF-IR is a physiological target for p53 in osteosarcoma cells. |
| 238 | 9492043 | The p53-induced regulation of IGF-IR levels was studied in a tetracycline-regulated expression system. |
| 239 | 9492043 | When expressed in Saos-2, osteosarcoma cells that lack p53, wild-type p53 decreased, whereas mutated p53 increased IGF-IR expression, and IGF-I-induced tyrosine phosphorylation of the IGF-IR. |
| 240 | 9492043 | Similarly, wild-type p53 decreased IGF-I-induced tyrosine phosphorylation of IRS-1. |
| 241 | 9492043 | A functional and physical interaction between p53 and Sp1, in the regulation of the IGF-R, was studied in osteosarcoma cells. |
| 242 | 9492043 | Expression of p53 decreased IGF-IR promoter activity, whereas no effect on promoter activity was seen by Sp1 expressed alone. |
| 243 | 9492043 | However, Sp1 counteracted the inhibitory effect of p53 on IGF-IR promoter activity in a dose-dependent manner. |
| 244 | 9492043 | Furthermore, wild-type and mutated p53 were coimmunoprecipitated with Sp1, indicating a physical interaction between p53 and Sp1. |
| 245 | 9492043 | In conclusion, p53 regulates IGF-IR expression, as reflected by a reduction in IGF-IR protein and a parallel reduction in IGF-I-induced tyrosine phosphorylation of the IGF-IR and IRS-1 in an osteosarcoma cell line. |
| 246 | 9492043 | These data indicate that the IGF-I receptor is a physiological target for p53 in osteosarcoma cells. |
| 247 | 9492043 | Furthermore, data supporting an interaction between p53 and Sp1 in the regulation of the promoter activity of IGF-IR are presented. |
| 248 | 9492043 | p53 regulates insulin-like growth factor-I (IGF-I) receptor expression and IGF-I-induced tyrosine phosphorylation in an osteosarcoma cell line: interaction between p53 and Sp1. |
| 249 | 9492043 | The insulin-like growth factor-I receptor (IGF-IR) is involved in tumorigenesis. |
| 250 | 9492043 | The aim of the present study was to investigate whether the IGF-IR is a physiological target for p53 in osteosarcoma cells. |
| 251 | 9492043 | The p53-induced regulation of IGF-IR levels was studied in a tetracycline-regulated expression system. |
| 252 | 9492043 | When expressed in Saos-2, osteosarcoma cells that lack p53, wild-type p53 decreased, whereas mutated p53 increased IGF-IR expression, and IGF-I-induced tyrosine phosphorylation of the IGF-IR. |
| 253 | 9492043 | Similarly, wild-type p53 decreased IGF-I-induced tyrosine phosphorylation of IRS-1. |
| 254 | 9492043 | A functional and physical interaction between p53 and Sp1, in the regulation of the IGF-R, was studied in osteosarcoma cells. |
| 255 | 9492043 | Expression of p53 decreased IGF-IR promoter activity, whereas no effect on promoter activity was seen by Sp1 expressed alone. |
| 256 | 9492043 | However, Sp1 counteracted the inhibitory effect of p53 on IGF-IR promoter activity in a dose-dependent manner. |
| 257 | 9492043 | Furthermore, wild-type and mutated p53 were coimmunoprecipitated with Sp1, indicating a physical interaction between p53 and Sp1. |
| 258 | 9492043 | In conclusion, p53 regulates IGF-IR expression, as reflected by a reduction in IGF-IR protein and a parallel reduction in IGF-I-induced tyrosine phosphorylation of the IGF-IR and IRS-1 in an osteosarcoma cell line. |
| 259 | 9492043 | These data indicate that the IGF-I receptor is a physiological target for p53 in osteosarcoma cells. |
| 260 | 9492043 | Furthermore, data supporting an interaction between p53 and Sp1 in the regulation of the promoter activity of IGF-IR are presented. |
| 261 | 9604870 | Octreotide prevents the early increase in renal insulin-like growth factor binding protein 1 in streptozotocin diabetic rats. |
| 262 | 9604870 | The early renal growth in streptozotocin (STZ)-induced diabetic rats is preceded by a transient rise in renal tissue insulin-like growth factor (IGF)-I concentration. |
| 263 | 9604870 | Administration of the long-acting somatostatin analog octreotide to STZ diabetic rats inhibits the early increase in kidney IGF-I and the increase in kidney size without affecting metabolic control. |
| 264 | 9604870 | Renal IGF-I mRNA was significantly decreased to the same extent in both diabetic groups 2 and 7 days after the induction of diabetes, while renal IGF-I receptor (IGF-IR) mRNA was unchanged in rats from either group. |
| 265 | 9604870 | Two days after induction of diabetes, renal insulin-like growth factor binding protein (IGFBP)-1 mRNA and 30-kDa IGFBPs (containing IGFBP-1) increased by 186 and 192%, respectively, in untreated diabetic animals compared with controls. |
| 266 | 9604870 | We conclude that the well-known inhibitory effect of octreotide on the early increase in renal IGF-I concentration and renal size in diabetes may be mediated through a direct effect on renal IGFBP-1 levels. |
| 267 | 9755596 | This study was undertaken to biochemically and immunohistochemically clarify the expression of basic fibroblast growth factor (bFGF), insulin-like growth factor-I (IGF-I), fibroblast growth factor receptor (bFGFR), insulin-like growth factor-I receptor (IGF-IR) and vascular smooth muscle cell (VSMC) growth by using Streptozotocin (STZ) treated rat serum. |
| 268 | 9755596 | Also according to western blot analysis, the protein synthesis of bFGFR and IGF-IR in the VSMCs was increased in STZ treated rat sera. |
| 269 | 9755596 | Immunohistochemically, bFGF, IGF-I and their receptors were much more localized in VSMCs in STZ treated rat sera than in control sera. |
| 270 | 9755596 | This study was undertaken to biochemically and immunohistochemically clarify the expression of basic fibroblast growth factor (bFGF), insulin-like growth factor-I (IGF-I), fibroblast growth factor receptor (bFGFR), insulin-like growth factor-I receptor (IGF-IR) and vascular smooth muscle cell (VSMC) growth by using Streptozotocin (STZ) treated rat serum. |
| 271 | 9755596 | Also according to western blot analysis, the protein synthesis of bFGFR and IGF-IR in the VSMCs was increased in STZ treated rat sera. |
| 272 | 9755596 | Immunohistochemically, bFGF, IGF-I and their receptors were much more localized in VSMCs in STZ treated rat sera than in control sera. |
| 273 | 9761714 | The expression of a number of genes encoding key players in insulin signalling and action, including insulin, insulin receptor (IR), downstream signalling molecules such as insulin receptor substrate-1 (IRS-1) and IRS-2, glucose transporters (GLUT4, GLUT2) and important metabolic enzymes such as glucokinase, has now been altered in transgenic or knockout mice. |
| 274 | 9761714 | Genes encoding insulin-like growth factors (IGF-I and IGF-II) and their type I receptor (IGF-IR) have also been disrupted. |
| 275 | 9761714 | However, IR could replace IGF-IR if efficiently activated by IGF-II. |
| 276 | 9761714 | Concerning the issues of specificity and redundancy, studies with cell lines derived from IRS-1-deficient mice showed that IRS-1 and IRS-2 are also not completely interchangeable. |
| 277 | 9761714 | The expression of a number of genes encoding key players in insulin signalling and action, including insulin, insulin receptor (IR), downstream signalling molecules such as insulin receptor substrate-1 (IRS-1) and IRS-2, glucose transporters (GLUT4, GLUT2) and important metabolic enzymes such as glucokinase, has now been altered in transgenic or knockout mice. |
| 278 | 9761714 | Genes encoding insulin-like growth factors (IGF-I and IGF-II) and their type I receptor (IGF-IR) have also been disrupted. |
| 279 | 9761714 | However, IR could replace IGF-IR if efficiently activated by IGF-II. |
| 280 | 9761714 | Concerning the issues of specificity and redundancy, studies with cell lines derived from IRS-1-deficient mice showed that IRS-1 and IRS-2 are also not completely interchangeable. |
| 281 | 9972281 | Insulin-like growth factor-I receptor signal transduction: at the interface between physiology and cell biology. |
| 282 | 9972281 | The insulin-like growth factor-I receptor (IGF-IR) mediates the biological actions of IGF-I and IGF-II. |
| 283 | 9972281 | The insulin-receptor substrate (IRS), SHC, GRB2, CRKII and CRKL adaptor proteins have all been implicated in transmitting signals to the nucleus of the cell. |
| 284 | 10036618 | [Biological and clinical analyses of the mechanism of growth retardation and the effect of recombinant human insulin-like growth factor-1 (rhIGF-1) treatment on glucose metabolism and growth in leprechaunism with severe insulin resistant diabetes]. |
| 285 | 10036618 | The patient's fibroblasts had normal binding of IGF-1, normal phosphorylation of the beta-subunit of IGF-1 receptor (IGF-1R) and normal incorporation of thymidine in response to IGF-1. |
| 286 | 10036618 | The subcutaneous administration of rhIGF-1 at the single dose of 0.4 mg/kg revealed a half life of IGF-1 as short as 90 minutes, and her serum IGFBP-3 level was extremely low. |
| 287 | 10036618 | The results suggested that the treatment with a high dose of rhIGF-1 by both SI and CSI is effective for preventing the postnatal growth retardation and normalizing glucose metabolism in patients with genetic form of extremely severe insulin resistant diabetes and that IGF-1 deficient state and partial GH resistance such as the impairment of the production of IGF-1 and IGFBP-3 may contribute to the growth retardation. |
| 288 | 10320380 | The compound was selective for insulin receptor versus insulin-like growth factor I (IGFI) receptor and other receptor tyrosine kinases. |
| 289 | 10329736 | Interaction of insulin receptor substrate 3 with insulin receptor, insulin receptor-related receptor, insulin-like growth factor-1 receptor, and downstream signaling proteins. |
| 290 | 10329736 | IRS3 is considerably shorter than IRS1, IRS2, and IRS4, and is predicted to interact with a distinct group of downstream signaling molecules. |
| 291 | 10329736 | As determined in a modified yeast two-hybrid system, mIRS3 bound strongly to the p85 subunit of phosphatidylinositol 3-kinase. |
| 292 | 10329736 | Although high affinity interaction required the presence of at least two of the four YXXM motifs in mIRS3, there was not a requirement for specific YXXM motifs. mIRS3 also bound to SHP2, Grb2, Nck, and Shc, but less strongly than to p85. |
| 293 | 10329736 | Insulin stimulation promoted the association of mIRS3 with p85, SHP2, Nck, and Shc. |
| 294 | 10329736 | Despite weak association between mIRS3 and Grb2, this interaction was not increased by insulin, and may not be mediated by the SH2 domain of Grb2. |
| 295 | 10329736 | Thus, in contrast to other IRS proteins, mIRS3 appears to have greater specificity for activation of the phosphatidylinositol 3-kinase pathway rather than the Grb2/Ras pathway. |
| 296 | 10417963 | Targeted gene mutations define the roles of insulin and IGF-I receptors in mouse embryonic development. |
| 297 | 10417963 | Insulin-like growth factors (IGFs) and their receptors regulate embryonic and post-natal growth. |
| 298 | 10417963 | Genetic evidence derived from targeted mouse mutants indicates that both the insulin receptor (IR) and IGF-I receptors (IGF-IRs) are required for mouse embryonic growth. |
| 299 | 10417963 | However, the roles of IRs and IGF-IRs are functionally distinct, with IGF-IRs mediating both IGF-I and IGF-II actions, and IRs mediating IGF-II, rather than insulin, action. |
| 300 | 10417963 | The combined interactions of IGF-IRs and IRs with IGF-I and IGF-II account for the entirety of the growth effects of these two ligands, and provide the molecular basis for IGFs-mediated intrauterine growth and differentiation. |
| 301 | 10417963 | Genetic ablation experiments of insulin receptor substrate-1 (IRS-1) and -2 (IRS-2), two important molecules in the IR and IGF-IR signaling pathways, are also beginning to shed light onto the mechanisms accounting for the specificity of IR and IGF-IR signaling. |
| 302 | 10471495 | Irs-2 coordinates Igf-1 receptor-mediated beta-cell development and peripheral insulin signalling. |
| 303 | 10471495 | Insulin receptor substrates (Irs proteins) mediate the pleiotropic effects of insulin and Igf-1 (insulin-like growth factor-1), including regulation of glucose homeostasis and cell growth and survival. |
| 304 | 10471495 | Our experiments revealed that Irs-1 and Irs-2 are critical for embryonic and post-natal growth, with Irs-1 having the predominant role. |
| 305 | 10471495 | By contrast, both Irs-1 and Irs-2 function in peripheral carbohydrate metabolism, but Irs-2 has the major role in beta-cell development and compensation for peripheral insulin resistance. |
| 306 | 10471495 | To establish a role for the Igf-1 receptor in beta-cells, we intercrossed mice heterozygous for null alleles of Igf1r and Irs2. |
| 307 | 10471495 | Our results reveal that Igf-1 receptors promote beta-cell development and survival through the Irs-2 signalling pathway. |
| 308 | 10471495 | Thus, Irs-2 integrates the effects of insulin in peripheral target tissues with Igf-1 in pancreatic beta-cells to maintain glucose homeostasis. |
| 309 | 10581081 | Regulation of vascular endothelial growth factor-dependent retinal neovascularization by insulin-like growth factor-1 receptor. |
| 310 | 10581081 | Although insulin-like growth factor 1 (IGF-1) has been associated with retinopathy, proof of a direct relationship has been lacking. |
| 311 | 10581081 | Here we show that an IGF-1 receptor antagonist suppresses retinal neovascularization in vivo, and infer that interactions between IGF-1 and the IGF-1 receptor are necessary for induction of maximal neovascularization by vascular endothelial growth factor (VEGF). |
| 312 | 10581081 | IGF-1 receptor regulation of VEGF action is mediated at least in part through control of VEGF activation of p44/42 mitogen-activated protein kinase, establishing a hierarchical relationship between IGF-1 and VEGF receptors. |
| 313 | 10581081 | IGF-1 levels, low in untreated diabetes, rise with insulin therapy, permitting VEGF-induced retinopathy. |
| 314 | 10770205 | Studies of the variability of the genes encoding the insulin-like growth factor I receptor and its ligand in relation to type 2 diabetes mellitus. |
| 315 | 10770205 | Insulin-like growth factor I (IGF-I) is an important regulator of many aspects of growth, differentiation, and development, and as low birth weight has been associated with impaired glucose tolerance and overt type 2 diabetes in adult life, we considered the genes encoding the IGF-I and the IGF-I receptor (IGF-IR) as candidates for low birth weight, insulin resistance, and type 2 diabetes. |
| 316 | 10770205 | Here we report the mutational analysis of the coding regions of the IGF-I and IGF-IR performed on genomic DNA from probands of 82 Danish type 2 diabetic families. |
| 317 | 10770205 | No mutations predicting changes in the amino acid sequences of the IGF-I or IGF-IR genes were detected, but several silent and intronic polymorphisms were found. |
| 318 | 10770205 | In conclusion, variability in the coding regions of IGF-I and the IGF-IR does not associate with reduced birth weight, insulin sensitivity index, or type 2 diabetes in the Danish population. |
| 319 | 10770205 | Studies of the variability of the genes encoding the insulin-like growth factor I receptor and its ligand in relation to type 2 diabetes mellitus. |
| 320 | 10770205 | Insulin-like growth factor I (IGF-I) is an important regulator of many aspects of growth, differentiation, and development, and as low birth weight has been associated with impaired glucose tolerance and overt type 2 diabetes in adult life, we considered the genes encoding the IGF-I and the IGF-I receptor (IGF-IR) as candidates for low birth weight, insulin resistance, and type 2 diabetes. |
| 321 | 10770205 | Here we report the mutational analysis of the coding regions of the IGF-I and IGF-IR performed on genomic DNA from probands of 82 Danish type 2 diabetic families. |
| 322 | 10770205 | No mutations predicting changes in the amino acid sequences of the IGF-I or IGF-IR genes were detected, but several silent and intronic polymorphisms were found. |
| 323 | 10770205 | In conclusion, variability in the coding regions of IGF-I and the IGF-IR does not associate with reduced birth weight, insulin sensitivity index, or type 2 diabetes in the Danish population. |
| 324 | 10770205 | Studies of the variability of the genes encoding the insulin-like growth factor I receptor and its ligand in relation to type 2 diabetes mellitus. |
| 325 | 10770205 | Insulin-like growth factor I (IGF-I) is an important regulator of many aspects of growth, differentiation, and development, and as low birth weight has been associated with impaired glucose tolerance and overt type 2 diabetes in adult life, we considered the genes encoding the IGF-I and the IGF-I receptor (IGF-IR) as candidates for low birth weight, insulin resistance, and type 2 diabetes. |
| 326 | 10770205 | Here we report the mutational analysis of the coding regions of the IGF-I and IGF-IR performed on genomic DNA from probands of 82 Danish type 2 diabetic families. |
| 327 | 10770205 | No mutations predicting changes in the amino acid sequences of the IGF-I or IGF-IR genes were detected, but several silent and intronic polymorphisms were found. |
| 328 | 10770205 | In conclusion, variability in the coding regions of IGF-I and the IGF-IR does not associate with reduced birth weight, insulin sensitivity index, or type 2 diabetes in the Danish population. |
| 329 | 10770205 | Studies of the variability of the genes encoding the insulin-like growth factor I receptor and its ligand in relation to type 2 diabetes mellitus. |
| 330 | 10770205 | Insulin-like growth factor I (IGF-I) is an important regulator of many aspects of growth, differentiation, and development, and as low birth weight has been associated with impaired glucose tolerance and overt type 2 diabetes in adult life, we considered the genes encoding the IGF-I and the IGF-I receptor (IGF-IR) as candidates for low birth weight, insulin resistance, and type 2 diabetes. |
| 331 | 10770205 | Here we report the mutational analysis of the coding regions of the IGF-I and IGF-IR performed on genomic DNA from probands of 82 Danish type 2 diabetic families. |
| 332 | 10770205 | No mutations predicting changes in the amino acid sequences of the IGF-I or IGF-IR genes were detected, but several silent and intronic polymorphisms were found. |
| 333 | 10770205 | In conclusion, variability in the coding regions of IGF-I and the IGF-IR does not associate with reduced birth weight, insulin sensitivity index, or type 2 diabetes in the Danish population. |
| 334 | 10862615 | Differential effects of low density lipoproteins on insulin-like growth factor-1 (IGF-1) and IGF-1 receptor expression in vascular smooth muscle cells. |
| 335 | 10862615 | Insulin-like growth factor-1 (IGF-1) is an autocrine/paracrine factor for vascular smooth muscle cells and has potent anti-apoptotic effects. |
| 336 | 10862615 | Thus, we hypothesized that part of the proliferative responses to LDLs may be explained by its modulation of IGF-1 or IGF-1 receptor (IGF-1R) expression. |
| 337 | 10862615 | Treatment of rat vascular smooth muscle cells with increasing doses of native LDL dose-dependently increased IGF-1 mRNA by up to 2.6-fold; however, native LDL had no effect on IGF-1R mRNA expression. |
| 338 | 10862615 | In contrast, the same doses of oxidized LDL significantly reduced IGF-1 and IGF-1R mRNA by 80 and 61%, respectively, and reduced IGF-1 and IGF-1R protein expression by 63 and 46%. |
| 339 | 10862615 | In summary, these results suggest that native and oxidized LDLs have differential effects on IGF-1 and IGF-1R expression. |
| 340 | 10862615 | Because IGF-1 is a potent survival factor for vascular smooth muscle cells, our findings suggest that moderately oxidized LDL may favor proliferation of smooth muscle cells, whereas oxidized LDL may contribute to plaque apoptosis by local depletion of IGF-1 and IGF-1R. |
| 341 | 10862615 | Differential effects of low density lipoproteins on insulin-like growth factor-1 (IGF-1) and IGF-1 receptor expression in vascular smooth muscle cells. |
| 342 | 10862615 | Insulin-like growth factor-1 (IGF-1) is an autocrine/paracrine factor for vascular smooth muscle cells and has potent anti-apoptotic effects. |
| 343 | 10862615 | Thus, we hypothesized that part of the proliferative responses to LDLs may be explained by its modulation of IGF-1 or IGF-1 receptor (IGF-1R) expression. |
| 344 | 10862615 | Treatment of rat vascular smooth muscle cells with increasing doses of native LDL dose-dependently increased IGF-1 mRNA by up to 2.6-fold; however, native LDL had no effect on IGF-1R mRNA expression. |
| 345 | 10862615 | In contrast, the same doses of oxidized LDL significantly reduced IGF-1 and IGF-1R mRNA by 80 and 61%, respectively, and reduced IGF-1 and IGF-1R protein expression by 63 and 46%. |
| 346 | 10862615 | In summary, these results suggest that native and oxidized LDLs have differential effects on IGF-1 and IGF-1R expression. |
| 347 | 10862615 | Because IGF-1 is a potent survival factor for vascular smooth muscle cells, our findings suggest that moderately oxidized LDL may favor proliferation of smooth muscle cells, whereas oxidized LDL may contribute to plaque apoptosis by local depletion of IGF-1 and IGF-1R. |
| 348 | 10862615 | Differential effects of low density lipoproteins on insulin-like growth factor-1 (IGF-1) and IGF-1 receptor expression in vascular smooth muscle cells. |
| 349 | 10862615 | Insulin-like growth factor-1 (IGF-1) is an autocrine/paracrine factor for vascular smooth muscle cells and has potent anti-apoptotic effects. |
| 350 | 10862615 | Thus, we hypothesized that part of the proliferative responses to LDLs may be explained by its modulation of IGF-1 or IGF-1 receptor (IGF-1R) expression. |
| 351 | 10862615 | Treatment of rat vascular smooth muscle cells with increasing doses of native LDL dose-dependently increased IGF-1 mRNA by up to 2.6-fold; however, native LDL had no effect on IGF-1R mRNA expression. |
| 352 | 10862615 | In contrast, the same doses of oxidized LDL significantly reduced IGF-1 and IGF-1R mRNA by 80 and 61%, respectively, and reduced IGF-1 and IGF-1R protein expression by 63 and 46%. |
| 353 | 10862615 | In summary, these results suggest that native and oxidized LDLs have differential effects on IGF-1 and IGF-1R expression. |
| 354 | 10862615 | Because IGF-1 is a potent survival factor for vascular smooth muscle cells, our findings suggest that moderately oxidized LDL may favor proliferation of smooth muscle cells, whereas oxidized LDL may contribute to plaque apoptosis by local depletion of IGF-1 and IGF-1R. |
| 355 | 10862615 | Differential effects of low density lipoproteins on insulin-like growth factor-1 (IGF-1) and IGF-1 receptor expression in vascular smooth muscle cells. |
| 356 | 10862615 | Insulin-like growth factor-1 (IGF-1) is an autocrine/paracrine factor for vascular smooth muscle cells and has potent anti-apoptotic effects. |
| 357 | 10862615 | Thus, we hypothesized that part of the proliferative responses to LDLs may be explained by its modulation of IGF-1 or IGF-1 receptor (IGF-1R) expression. |
| 358 | 10862615 | Treatment of rat vascular smooth muscle cells with increasing doses of native LDL dose-dependently increased IGF-1 mRNA by up to 2.6-fold; however, native LDL had no effect on IGF-1R mRNA expression. |
| 359 | 10862615 | In contrast, the same doses of oxidized LDL significantly reduced IGF-1 and IGF-1R mRNA by 80 and 61%, respectively, and reduced IGF-1 and IGF-1R protein expression by 63 and 46%. |
| 360 | 10862615 | In summary, these results suggest that native and oxidized LDLs have differential effects on IGF-1 and IGF-1R expression. |
| 361 | 10862615 | Because IGF-1 is a potent survival factor for vascular smooth muscle cells, our findings suggest that moderately oxidized LDL may favor proliferation of smooth muscle cells, whereas oxidized LDL may contribute to plaque apoptosis by local depletion of IGF-1 and IGF-1R. |
| 362 | 10862615 | Differential effects of low density lipoproteins on insulin-like growth factor-1 (IGF-1) and IGF-1 receptor expression in vascular smooth muscle cells. |
| 363 | 10862615 | Insulin-like growth factor-1 (IGF-1) is an autocrine/paracrine factor for vascular smooth muscle cells and has potent anti-apoptotic effects. |
| 364 | 10862615 | Thus, we hypothesized that part of the proliferative responses to LDLs may be explained by its modulation of IGF-1 or IGF-1 receptor (IGF-1R) expression. |
| 365 | 10862615 | Treatment of rat vascular smooth muscle cells with increasing doses of native LDL dose-dependently increased IGF-1 mRNA by up to 2.6-fold; however, native LDL had no effect on IGF-1R mRNA expression. |
| 366 | 10862615 | In contrast, the same doses of oxidized LDL significantly reduced IGF-1 and IGF-1R mRNA by 80 and 61%, respectively, and reduced IGF-1 and IGF-1R protein expression by 63 and 46%. |
| 367 | 10862615 | In summary, these results suggest that native and oxidized LDLs have differential effects on IGF-1 and IGF-1R expression. |
| 368 | 10862615 | Because IGF-1 is a potent survival factor for vascular smooth muscle cells, our findings suggest that moderately oxidized LDL may favor proliferation of smooth muscle cells, whereas oxidized LDL may contribute to plaque apoptosis by local depletion of IGF-1 and IGF-1R. |
| 369 | 10886503 | Differential roles of insulin receptor and insulin-like growth factor-1 receptor in differentiation of murine skin keratinocytes. |
| 370 | 10886503 | The insulin receptor and the insulin-like growth factor-1 receptor are widely expressed tyrosine kinases that mediate insulin and insulin-like growth factor-1 signaling. |
| 371 | 10886503 | We have studied the regulation of insulin receptor and insulin-like growth factor-1 receptor in the differentiation of cultured murine keratinocytes. |
| 372 | 10886503 | Insulin binding to skin keratinocytes, however, increased during calcium-induced differentiation, whereas insulin-like growth factor-1 binding decreased. |
| 373 | 10886503 | In proliferating keratinocytes both receptors became phosphorylated upon ligand binding, insulin-like growth factor-1 receptor to a greater extent. |
| 374 | 10886503 | Terminal differentiation resulted in a decrease in insulin receptor autophosphorylation, whereas insulin-like growth factor-1 receptor autophosphorylation was abolished. |
| 375 | 10886503 | Finally, due to the change in the receptor's activity during keratinocyte differentiation, the role of insulin and insulin-like growth factor-1 in the differentiation process was examined. |
| 376 | 10886503 | The expected increase in the expression of keratins 1 and 10 during calcium-induced differentiation was facilitated in the presence of insulin, whereas this induction was inhibited in the presence of insulin-like growth factor-1. |
| 377 | 10886503 | In conclusion, these results demonstrate that insulin and insulin-like growth factor-1 signaling pathways are differentially involved in skin differentiation, suggesting that abnormal insulin signaling, as occurs in diabetes, may lead to skin pathology. |
| 378 | 10886503 | Differential roles of insulin receptor and insulin-like growth factor-1 receptor in differentiation of murine skin keratinocytes. |
| 379 | 10886503 | The insulin receptor and the insulin-like growth factor-1 receptor are widely expressed tyrosine kinases that mediate insulin and insulin-like growth factor-1 signaling. |
| 380 | 10886503 | We have studied the regulation of insulin receptor and insulin-like growth factor-1 receptor in the differentiation of cultured murine keratinocytes. |
| 381 | 10886503 | Insulin binding to skin keratinocytes, however, increased during calcium-induced differentiation, whereas insulin-like growth factor-1 binding decreased. |
| 382 | 10886503 | In proliferating keratinocytes both receptors became phosphorylated upon ligand binding, insulin-like growth factor-1 receptor to a greater extent. |
| 383 | 10886503 | Terminal differentiation resulted in a decrease in insulin receptor autophosphorylation, whereas insulin-like growth factor-1 receptor autophosphorylation was abolished. |
| 384 | 10886503 | Finally, due to the change in the receptor's activity during keratinocyte differentiation, the role of insulin and insulin-like growth factor-1 in the differentiation process was examined. |
| 385 | 10886503 | The expected increase in the expression of keratins 1 and 10 during calcium-induced differentiation was facilitated in the presence of insulin, whereas this induction was inhibited in the presence of insulin-like growth factor-1. |
| 386 | 10886503 | In conclusion, these results demonstrate that insulin and insulin-like growth factor-1 signaling pathways are differentially involved in skin differentiation, suggesting that abnormal insulin signaling, as occurs in diabetes, may lead to skin pathology. |
| 387 | 10886503 | Differential roles of insulin receptor and insulin-like growth factor-1 receptor in differentiation of murine skin keratinocytes. |
| 388 | 10886503 | The insulin receptor and the insulin-like growth factor-1 receptor are widely expressed tyrosine kinases that mediate insulin and insulin-like growth factor-1 signaling. |
| 389 | 10886503 | We have studied the regulation of insulin receptor and insulin-like growth factor-1 receptor in the differentiation of cultured murine keratinocytes. |
| 390 | 10886503 | Insulin binding to skin keratinocytes, however, increased during calcium-induced differentiation, whereas insulin-like growth factor-1 binding decreased. |
| 391 | 10886503 | In proliferating keratinocytes both receptors became phosphorylated upon ligand binding, insulin-like growth factor-1 receptor to a greater extent. |
| 392 | 10886503 | Terminal differentiation resulted in a decrease in insulin receptor autophosphorylation, whereas insulin-like growth factor-1 receptor autophosphorylation was abolished. |
| 393 | 10886503 | Finally, due to the change in the receptor's activity during keratinocyte differentiation, the role of insulin and insulin-like growth factor-1 in the differentiation process was examined. |
| 394 | 10886503 | The expected increase in the expression of keratins 1 and 10 during calcium-induced differentiation was facilitated in the presence of insulin, whereas this induction was inhibited in the presence of insulin-like growth factor-1. |
| 395 | 10886503 | In conclusion, these results demonstrate that insulin and insulin-like growth factor-1 signaling pathways are differentially involved in skin differentiation, suggesting that abnormal insulin signaling, as occurs in diabetes, may lead to skin pathology. |
| 396 | 10886503 | Differential roles of insulin receptor and insulin-like growth factor-1 receptor in differentiation of murine skin keratinocytes. |
| 397 | 10886503 | The insulin receptor and the insulin-like growth factor-1 receptor are widely expressed tyrosine kinases that mediate insulin and insulin-like growth factor-1 signaling. |
| 398 | 10886503 | We have studied the regulation of insulin receptor and insulin-like growth factor-1 receptor in the differentiation of cultured murine keratinocytes. |
| 399 | 10886503 | Insulin binding to skin keratinocytes, however, increased during calcium-induced differentiation, whereas insulin-like growth factor-1 binding decreased. |
| 400 | 10886503 | In proliferating keratinocytes both receptors became phosphorylated upon ligand binding, insulin-like growth factor-1 receptor to a greater extent. |
| 401 | 10886503 | Terminal differentiation resulted in a decrease in insulin receptor autophosphorylation, whereas insulin-like growth factor-1 receptor autophosphorylation was abolished. |
| 402 | 10886503 | Finally, due to the change in the receptor's activity during keratinocyte differentiation, the role of insulin and insulin-like growth factor-1 in the differentiation process was examined. |
| 403 | 10886503 | The expected increase in the expression of keratins 1 and 10 during calcium-induced differentiation was facilitated in the presence of insulin, whereas this induction was inhibited in the presence of insulin-like growth factor-1. |
| 404 | 10886503 | In conclusion, these results demonstrate that insulin and insulin-like growth factor-1 signaling pathways are differentially involved in skin differentiation, suggesting that abnormal insulin signaling, as occurs in diabetes, may lead to skin pathology. |
| 405 | 10886503 | Differential roles of insulin receptor and insulin-like growth factor-1 receptor in differentiation of murine skin keratinocytes. |
| 406 | 10886503 | The insulin receptor and the insulin-like growth factor-1 receptor are widely expressed tyrosine kinases that mediate insulin and insulin-like growth factor-1 signaling. |
| 407 | 10886503 | We have studied the regulation of insulin receptor and insulin-like growth factor-1 receptor in the differentiation of cultured murine keratinocytes. |
| 408 | 10886503 | Insulin binding to skin keratinocytes, however, increased during calcium-induced differentiation, whereas insulin-like growth factor-1 binding decreased. |
| 409 | 10886503 | In proliferating keratinocytes both receptors became phosphorylated upon ligand binding, insulin-like growth factor-1 receptor to a greater extent. |
| 410 | 10886503 | Terminal differentiation resulted in a decrease in insulin receptor autophosphorylation, whereas insulin-like growth factor-1 receptor autophosphorylation was abolished. |
| 411 | 10886503 | Finally, due to the change in the receptor's activity during keratinocyte differentiation, the role of insulin and insulin-like growth factor-1 in the differentiation process was examined. |
| 412 | 10886503 | The expected increase in the expression of keratins 1 and 10 during calcium-induced differentiation was facilitated in the presence of insulin, whereas this induction was inhibited in the presence of insulin-like growth factor-1. |
| 413 | 10886503 | In conclusion, these results demonstrate that insulin and insulin-like growth factor-1 signaling pathways are differentially involved in skin differentiation, suggesting that abnormal insulin signaling, as occurs in diabetes, may lead to skin pathology. |
| 414 | 11147784 | IGF-I promotes the survival of multiple cell types by activating the IGF-I receptor (IGF-IR), which signals downstream to a serine/threonine kinase termed Akt. |
| 415 | 11147784 | Hence, in the retina of diabetic rats, as in the retina of diabetic human donors, IGF-I mRNA levels are substantially lower than in age-matched nondiabetic controls, whereas IGF-IR activation and signaling are not affected, at least for some time. |
| 416 | 11147784 | This finding suggests that in the diabetic retina, the activation of the IGF-IR is modulated by influences that compensate for, or are compensated by, decreased IGF-I synthesis. |
| 417 | 11147784 | IGF-I promotes the survival of multiple cell types by activating the IGF-I receptor (IGF-IR), which signals downstream to a serine/threonine kinase termed Akt. |
| 418 | 11147784 | Hence, in the retina of diabetic rats, as in the retina of diabetic human donors, IGF-I mRNA levels are substantially lower than in age-matched nondiabetic controls, whereas IGF-IR activation and signaling are not affected, at least for some time. |
| 419 | 11147784 | This finding suggests that in the diabetic retina, the activation of the IGF-IR is modulated by influences that compensate for, or are compensated by, decreased IGF-I synthesis. |
| 420 | 11147784 | IGF-I promotes the survival of multiple cell types by activating the IGF-I receptor (IGF-IR), which signals downstream to a serine/threonine kinase termed Akt. |
| 421 | 11147784 | Hence, in the retina of diabetic rats, as in the retina of diabetic human donors, IGF-I mRNA levels are substantially lower than in age-matched nondiabetic controls, whereas IGF-IR activation and signaling are not affected, at least for some time. |
| 422 | 11147784 | This finding suggests that in the diabetic retina, the activation of the IGF-IR is modulated by influences that compensate for, or are compensated by, decreased IGF-I synthesis. |
| 423 | 11493020 | Insulin-like growth factor-I in muscle metabolism and myotherapies. |
| 424 | 11493020 | The critical anabolic and trophic role of signaling by insulin-like growth factors (IGF) I and II via the type-I IGF receptor (IGF-IR) is reviewed throughout the life of skeletal myocytes. |
| 425 | 11739335 | Distinct and overlapping functions of insulin and IGF-I receptors. |
| 426 | 11739335 | IGF-I receptor mediates IGF-I and IGF-II action on prenatal growth and IGF-I action on postnatal growth. |
| 427 | 11739335 | Insulin receptor mediates prenatal growth in response to IGF-II and postnatal metabolism in response to insulin. |
| 428 | 11739335 | The ability of the insulin receptor to act as a bona fide IGF-II-dependent growth promoter is underscored by its rescue of double knockout Igf1r/Igf2r mice. |
| 429 | 11739335 | Thus, IGF-II is a true bifunctional ligand that is able to stimulate both insulin and IGF-I receptor signaling, although with different potencies. |
| 430 | 11739335 | In contrast, the IGF-II/cation-independent mannose-6-phosphate receptor regulates IGF-II clearance. |
| 431 | 11739335 | The growth retardation of mice lacking IGF-I and/or insulin receptors is due to reduced cell number, resulting from decreased proliferation. |
| 432 | 11822821 | Testosterone stimulates growth of tibial epiphyseal growth plate and insulin-like growth factor-1 receptor abundance in hypophysectomized and castrated rats. |
| 433 | 11822821 | Puberty is associated with an increase in the plasma concentration of sex steroids, growth hormone (GH), and insulin-like growth factor-1 (IGF-1). |
| 434 | 11822821 | However, testosterone increased in a dose-dependent manner the abundance of IGF-1 receptor EGP. |
| 435 | 11872675 | Increased insulin sensitivity in IGF-I receptor--deficient brown adipocytes. |
| 436 | 11872675 | Immortalized brown adipocyte cell lines have been generated from fetuses of mice deficient in the insulin-like growth factor I receptor gene (IGF-IR(-/-)), as well as from fetuses of wild-type mice (IGF-IR(+/+)). |
| 437 | 11872675 | IGF-IR(-/-) brown adipocytes lacked IGF-IR protein expression; insulin receptor (IR) expression remained unchanged as compared with wild-type cells. |
| 438 | 11872675 | Upon insulin stimulation, tyrosine phosphorylation of (insulin receptor substrate-1) IRS-1 was much higher in IGF-IR(-/-) brown adipocytes, although IRS-1 protein content was reduced. |
| 439 | 11872675 | Downstream, the association IRS-1/growth factor receptor binding protein-2 (Grb-2) was augmented in the IGF-IR(-/-) brown adipocyte cell line. |
| 440 | 11872675 | However, SHC expression and SHC tyrosine phosphorylation and its association with Grb-2 were unaltered in response to insulin in IGF-IR--deficient brown adipocytes. |
| 441 | 11872675 | These cells also showed an enhanced activation of mitogen-activated protein kinase (MAPK) kinase (MEK1/2) and p42/p44 mitogen-activated protein kinase (MAPK) upon insulin stimulation. |
| 442 | 11872675 | In addition, the lack of IGF-IR in brown adipocytes resulted in a higher mitogenic response (DNA synthesis, cell number, and proliferating cell nuclear antigen expression) to insulin than wild-type cells. |
| 443 | 11872675 | Finally, cells lacking IGF-IR showed a much lower association between IR or IRS-1 and phosphotyrosine phosphatase 1B (PTP1B) and also a decreased PTP1B activity upon insulin stimulation. |
| 444 | 11872675 | However, PTP1B/Grb-2 association remained unchanged in both cell types, regardless of insulin stimulation. |
| 445 | 11872675 | Data presented here provide strong evidence that IGF-IR--deficient brown adipocytes show an increased insulin sensitivity via IRS-1/Grb-2/MAPK, resulting in an increased mitogenesis in response to insulin. |
| 446 | 11872675 | Increased insulin sensitivity in IGF-I receptor--deficient brown adipocytes. |
| 447 | 11872675 | Immortalized brown adipocyte cell lines have been generated from fetuses of mice deficient in the insulin-like growth factor I receptor gene (IGF-IR(-/-)), as well as from fetuses of wild-type mice (IGF-IR(+/+)). |
| 448 | 11872675 | IGF-IR(-/-) brown adipocytes lacked IGF-IR protein expression; insulin receptor (IR) expression remained unchanged as compared with wild-type cells. |
| 449 | 11872675 | Upon insulin stimulation, tyrosine phosphorylation of (insulin receptor substrate-1) IRS-1 was much higher in IGF-IR(-/-) brown adipocytes, although IRS-1 protein content was reduced. |
| 450 | 11872675 | Downstream, the association IRS-1/growth factor receptor binding protein-2 (Grb-2) was augmented in the IGF-IR(-/-) brown adipocyte cell line. |
| 451 | 11872675 | However, SHC expression and SHC tyrosine phosphorylation and its association with Grb-2 were unaltered in response to insulin in IGF-IR--deficient brown adipocytes. |
| 452 | 11872675 | These cells also showed an enhanced activation of mitogen-activated protein kinase (MAPK) kinase (MEK1/2) and p42/p44 mitogen-activated protein kinase (MAPK) upon insulin stimulation. |
| 453 | 11872675 | In addition, the lack of IGF-IR in brown adipocytes resulted in a higher mitogenic response (DNA synthesis, cell number, and proliferating cell nuclear antigen expression) to insulin than wild-type cells. |
| 454 | 11872675 | Finally, cells lacking IGF-IR showed a much lower association between IR or IRS-1 and phosphotyrosine phosphatase 1B (PTP1B) and also a decreased PTP1B activity upon insulin stimulation. |
| 455 | 11872675 | However, PTP1B/Grb-2 association remained unchanged in both cell types, regardless of insulin stimulation. |
| 456 | 11872675 | Data presented here provide strong evidence that IGF-IR--deficient brown adipocytes show an increased insulin sensitivity via IRS-1/Grb-2/MAPK, resulting in an increased mitogenesis in response to insulin. |
| 457 | 11872675 | Increased insulin sensitivity in IGF-I receptor--deficient brown adipocytes. |
| 458 | 11872675 | Immortalized brown adipocyte cell lines have been generated from fetuses of mice deficient in the insulin-like growth factor I receptor gene (IGF-IR(-/-)), as well as from fetuses of wild-type mice (IGF-IR(+/+)). |
| 459 | 11872675 | IGF-IR(-/-) brown adipocytes lacked IGF-IR protein expression; insulin receptor (IR) expression remained unchanged as compared with wild-type cells. |
| 460 | 11872675 | Upon insulin stimulation, tyrosine phosphorylation of (insulin receptor substrate-1) IRS-1 was much higher in IGF-IR(-/-) brown adipocytes, although IRS-1 protein content was reduced. |
| 461 | 11872675 | Downstream, the association IRS-1/growth factor receptor binding protein-2 (Grb-2) was augmented in the IGF-IR(-/-) brown adipocyte cell line. |
| 462 | 11872675 | However, SHC expression and SHC tyrosine phosphorylation and its association with Grb-2 were unaltered in response to insulin in IGF-IR--deficient brown adipocytes. |
| 463 | 11872675 | These cells also showed an enhanced activation of mitogen-activated protein kinase (MAPK) kinase (MEK1/2) and p42/p44 mitogen-activated protein kinase (MAPK) upon insulin stimulation. |
| 464 | 11872675 | In addition, the lack of IGF-IR in brown adipocytes resulted in a higher mitogenic response (DNA synthesis, cell number, and proliferating cell nuclear antigen expression) to insulin than wild-type cells. |
| 465 | 11872675 | Finally, cells lacking IGF-IR showed a much lower association between IR or IRS-1 and phosphotyrosine phosphatase 1B (PTP1B) and also a decreased PTP1B activity upon insulin stimulation. |
| 466 | 11872675 | However, PTP1B/Grb-2 association remained unchanged in both cell types, regardless of insulin stimulation. |
| 467 | 11872675 | Data presented here provide strong evidence that IGF-IR--deficient brown adipocytes show an increased insulin sensitivity via IRS-1/Grb-2/MAPK, resulting in an increased mitogenesis in response to insulin. |
| 468 | 11872675 | Increased insulin sensitivity in IGF-I receptor--deficient brown adipocytes. |
| 469 | 11872675 | Immortalized brown adipocyte cell lines have been generated from fetuses of mice deficient in the insulin-like growth factor I receptor gene (IGF-IR(-/-)), as well as from fetuses of wild-type mice (IGF-IR(+/+)). |
| 470 | 11872675 | IGF-IR(-/-) brown adipocytes lacked IGF-IR protein expression; insulin receptor (IR) expression remained unchanged as compared with wild-type cells. |
| 471 | 11872675 | Upon insulin stimulation, tyrosine phosphorylation of (insulin receptor substrate-1) IRS-1 was much higher in IGF-IR(-/-) brown adipocytes, although IRS-1 protein content was reduced. |
| 472 | 11872675 | Downstream, the association IRS-1/growth factor receptor binding protein-2 (Grb-2) was augmented in the IGF-IR(-/-) brown adipocyte cell line. |
| 473 | 11872675 | However, SHC expression and SHC tyrosine phosphorylation and its association with Grb-2 were unaltered in response to insulin in IGF-IR--deficient brown adipocytes. |
| 474 | 11872675 | These cells also showed an enhanced activation of mitogen-activated protein kinase (MAPK) kinase (MEK1/2) and p42/p44 mitogen-activated protein kinase (MAPK) upon insulin stimulation. |
| 475 | 11872675 | In addition, the lack of IGF-IR in brown adipocytes resulted in a higher mitogenic response (DNA synthesis, cell number, and proliferating cell nuclear antigen expression) to insulin than wild-type cells. |
| 476 | 11872675 | Finally, cells lacking IGF-IR showed a much lower association between IR or IRS-1 and phosphotyrosine phosphatase 1B (PTP1B) and also a decreased PTP1B activity upon insulin stimulation. |
| 477 | 11872675 | However, PTP1B/Grb-2 association remained unchanged in both cell types, regardless of insulin stimulation. |
| 478 | 11872675 | Data presented here provide strong evidence that IGF-IR--deficient brown adipocytes show an increased insulin sensitivity via IRS-1/Grb-2/MAPK, resulting in an increased mitogenesis in response to insulin. |
| 479 | 11872675 | Increased insulin sensitivity in IGF-I receptor--deficient brown adipocytes. |
| 480 | 11872675 | Immortalized brown adipocyte cell lines have been generated from fetuses of mice deficient in the insulin-like growth factor I receptor gene (IGF-IR(-/-)), as well as from fetuses of wild-type mice (IGF-IR(+/+)). |
| 481 | 11872675 | IGF-IR(-/-) brown adipocytes lacked IGF-IR protein expression; insulin receptor (IR) expression remained unchanged as compared with wild-type cells. |
| 482 | 11872675 | Upon insulin stimulation, tyrosine phosphorylation of (insulin receptor substrate-1) IRS-1 was much higher in IGF-IR(-/-) brown adipocytes, although IRS-1 protein content was reduced. |
| 483 | 11872675 | Downstream, the association IRS-1/growth factor receptor binding protein-2 (Grb-2) was augmented in the IGF-IR(-/-) brown adipocyte cell line. |
| 484 | 11872675 | However, SHC expression and SHC tyrosine phosphorylation and its association with Grb-2 were unaltered in response to insulin in IGF-IR--deficient brown adipocytes. |
| 485 | 11872675 | These cells also showed an enhanced activation of mitogen-activated protein kinase (MAPK) kinase (MEK1/2) and p42/p44 mitogen-activated protein kinase (MAPK) upon insulin stimulation. |
| 486 | 11872675 | In addition, the lack of IGF-IR in brown adipocytes resulted in a higher mitogenic response (DNA synthesis, cell number, and proliferating cell nuclear antigen expression) to insulin than wild-type cells. |
| 487 | 11872675 | Finally, cells lacking IGF-IR showed a much lower association between IR or IRS-1 and phosphotyrosine phosphatase 1B (PTP1B) and also a decreased PTP1B activity upon insulin stimulation. |
| 488 | 11872675 | However, PTP1B/Grb-2 association remained unchanged in both cell types, regardless of insulin stimulation. |
| 489 | 11872675 | Data presented here provide strong evidence that IGF-IR--deficient brown adipocytes show an increased insulin sensitivity via IRS-1/Grb-2/MAPK, resulting in an increased mitogenesis in response to insulin. |
| 490 | 11872675 | Increased insulin sensitivity in IGF-I receptor--deficient brown adipocytes. |
| 491 | 11872675 | Immortalized brown adipocyte cell lines have been generated from fetuses of mice deficient in the insulin-like growth factor I receptor gene (IGF-IR(-/-)), as well as from fetuses of wild-type mice (IGF-IR(+/+)). |
| 492 | 11872675 | IGF-IR(-/-) brown adipocytes lacked IGF-IR protein expression; insulin receptor (IR) expression remained unchanged as compared with wild-type cells. |
| 493 | 11872675 | Upon insulin stimulation, tyrosine phosphorylation of (insulin receptor substrate-1) IRS-1 was much higher in IGF-IR(-/-) brown adipocytes, although IRS-1 protein content was reduced. |
| 494 | 11872675 | Downstream, the association IRS-1/growth factor receptor binding protein-2 (Grb-2) was augmented in the IGF-IR(-/-) brown adipocyte cell line. |
| 495 | 11872675 | However, SHC expression and SHC tyrosine phosphorylation and its association with Grb-2 were unaltered in response to insulin in IGF-IR--deficient brown adipocytes. |
| 496 | 11872675 | These cells also showed an enhanced activation of mitogen-activated protein kinase (MAPK) kinase (MEK1/2) and p42/p44 mitogen-activated protein kinase (MAPK) upon insulin stimulation. |
| 497 | 11872675 | In addition, the lack of IGF-IR in brown adipocytes resulted in a higher mitogenic response (DNA synthesis, cell number, and proliferating cell nuclear antigen expression) to insulin than wild-type cells. |
| 498 | 11872675 | Finally, cells lacking IGF-IR showed a much lower association between IR or IRS-1 and phosphotyrosine phosphatase 1B (PTP1B) and also a decreased PTP1B activity upon insulin stimulation. |
| 499 | 11872675 | However, PTP1B/Grb-2 association remained unchanged in both cell types, regardless of insulin stimulation. |
| 500 | 11872675 | Data presented here provide strong evidence that IGF-IR--deficient brown adipocytes show an increased insulin sensitivity via IRS-1/Grb-2/MAPK, resulting in an increased mitogenesis in response to insulin. |
| 501 | 11923875 | beta-cell-specific deletion of the Igf1 receptor leads to hyperinsulinemia and glucose intolerance but does not alter beta-cell mass. |
| 502 | 11923875 | Insulin-like growth factor 1 (Igf1) has been implicated in islet development and differentiated function, but the factors controlling this process are poorly understood. |
| 503 | 11923875 | Pancreatic islets produce Igf1 and Igf2, which bind to specific receptors on beta-cells. |
| 504 | 11923875 | Igf1 has been shown to influence beta-cell apoptosis, and both Igf1 and Igf2 increase islet growth; Igf2 does so in a manner additive with fibroblast growth factor 2 (ref. 10). |
| 505 | 11923875 | When mice deficient for the Igf1 receptor (Igf1r(+/-)) are bred with mice lacking insulin receptor substrate 2 (Irs2(-/-)), the resulting compound knockout mice show a reduction in mass of beta-cells similar to that observed in pancreas of Igf1r(-/-) mice (ref. 11), suggesting a role for Igf1r in growth of beta-cells. |
| 506 | 11923875 | To directly define the role of Igf1, we have created a mouse with a beta-cell-specific knockout of Igf1r (betaIgf1r(-/-)). |
| 507 | 11923875 | These mice show normal growth and development of beta-cells, but have reduced expression of Slc2a2 (also known as Glut2) and Gck (encoding glucokinase) in beta-cells, which results in defective glucose-stimulated insulin secretion and impaired glucose tolerance. |
| 508 | 11923875 | beta-cell-specific deletion of the Igf1 receptor leads to hyperinsulinemia and glucose intolerance but does not alter beta-cell mass. |
| 509 | 11923875 | Insulin-like growth factor 1 (Igf1) has been implicated in islet development and differentiated function, but the factors controlling this process are poorly understood. |
| 510 | 11923875 | Pancreatic islets produce Igf1 and Igf2, which bind to specific receptors on beta-cells. |
| 511 | 11923875 | Igf1 has been shown to influence beta-cell apoptosis, and both Igf1 and Igf2 increase islet growth; Igf2 does so in a manner additive with fibroblast growth factor 2 (ref. 10). |
| 512 | 11923875 | When mice deficient for the Igf1 receptor (Igf1r(+/-)) are bred with mice lacking insulin receptor substrate 2 (Irs2(-/-)), the resulting compound knockout mice show a reduction in mass of beta-cells similar to that observed in pancreas of Igf1r(-/-) mice (ref. 11), suggesting a role for Igf1r in growth of beta-cells. |
| 513 | 11923875 | To directly define the role of Igf1, we have created a mouse with a beta-cell-specific knockout of Igf1r (betaIgf1r(-/-)). |
| 514 | 11923875 | These mice show normal growth and development of beta-cells, but have reduced expression of Slc2a2 (also known as Glut2) and Gck (encoding glucokinase) in beta-cells, which results in defective glucose-stimulated insulin secretion and impaired glucose tolerance. |
| 515 | 11923875 | beta-cell-specific deletion of the Igf1 receptor leads to hyperinsulinemia and glucose intolerance but does not alter beta-cell mass. |
| 516 | 11923875 | Insulin-like growth factor 1 (Igf1) has been implicated in islet development and differentiated function, but the factors controlling this process are poorly understood. |
| 517 | 11923875 | Pancreatic islets produce Igf1 and Igf2, which bind to specific receptors on beta-cells. |
| 518 | 11923875 | Igf1 has been shown to influence beta-cell apoptosis, and both Igf1 and Igf2 increase islet growth; Igf2 does so in a manner additive with fibroblast growth factor 2 (ref. 10). |
| 519 | 11923875 | When mice deficient for the Igf1 receptor (Igf1r(+/-)) are bred with mice lacking insulin receptor substrate 2 (Irs2(-/-)), the resulting compound knockout mice show a reduction in mass of beta-cells similar to that observed in pancreas of Igf1r(-/-) mice (ref. 11), suggesting a role for Igf1r in growth of beta-cells. |
| 520 | 11923875 | To directly define the role of Igf1, we have created a mouse with a beta-cell-specific knockout of Igf1r (betaIgf1r(-/-)). |
| 521 | 11923875 | These mice show normal growth and development of beta-cells, but have reduced expression of Slc2a2 (also known as Glut2) and Gck (encoding glucokinase) in beta-cells, which results in defective glucose-stimulated insulin secretion and impaired glucose tolerance. |
| 522 | 12086849 | In a prototypical model of multistage tumorigenesis involving pancreatic islets in RIP1-Tag2 transgenic mice, activation of insulin-like growth factor II (IGF-II) was previously shown to serve as a survival factor that inhibited apoptosis. |
| 523 | 12086849 | Now IGF-1R, the receptor tyrosine kinase for IGF-II, has been found to be variably upregulated, first uniformly in dysplastic and angiogenic progenitors and then focally at the margins and in invasive regions of carcinomas. |
| 524 | 12137925 | These abnormalities were associated with DNA fragmentation, positive TUNEL staining, elevated Bax/Bcl-x(L) ratio, increased caspase 3 activities and decreased neuronal densities in diabetic hippocampi. |
| 525 | 12137925 | Western blotting and in situ hybridization revealed significant reductions in the expression of IGF-I, IGF-II, IGF-IR and IR preceding (2 months) and accompanying (8 months) the functional cognitive impairments and the apoptotic neuronal loss in hippocampus. |
| 526 | 12352620 | In this study, we examined the expression of insulin-like growth factor I (IGF-I) and its receptor (IGF-IR) in dorsal root ganglia (DRG) neurons in two rodent models of nerve injury: sciatic nerve axotomy and streptozotocin-induced (STZ) painful diabetic neuropathy. |
| 527 | 12352620 | There is a significant down-regulation in the expression of IGF-I and IGF-IR in the small DRG neurons of STZ rats by 59% and 71%, respectively. |
| 528 | 12352620 | A parallel reduction in expression is shown in axotomized < 25 microm diameter DRG neurons for IGF-I (47%) but not for IGF-IR. |
| 529 | 12352620 | In this study, we examined the expression of insulin-like growth factor I (IGF-I) and its receptor (IGF-IR) in dorsal root ganglia (DRG) neurons in two rodent models of nerve injury: sciatic nerve axotomy and streptozotocin-induced (STZ) painful diabetic neuropathy. |
| 530 | 12352620 | There is a significant down-regulation in the expression of IGF-I and IGF-IR in the small DRG neurons of STZ rats by 59% and 71%, respectively. |
| 531 | 12352620 | A parallel reduction in expression is shown in axotomized < 25 microm diameter DRG neurons for IGF-I (47%) but not for IGF-IR. |
| 532 | 12352620 | In this study, we examined the expression of insulin-like growth factor I (IGF-I) and its receptor (IGF-IR) in dorsal root ganglia (DRG) neurons in two rodent models of nerve injury: sciatic nerve axotomy and streptozotocin-induced (STZ) painful diabetic neuropathy. |
| 533 | 12352620 | There is a significant down-regulation in the expression of IGF-I and IGF-IR in the small DRG neurons of STZ rats by 59% and 71%, respectively. |
| 534 | 12352620 | A parallel reduction in expression is shown in axotomized < 25 microm diameter DRG neurons for IGF-I (47%) but not for IGF-IR. |
| 535 | 12360255 | Structural biology of insulin and IGF1 receptors: implications for drug design. |
| 536 | 12360255 | Here, we discuss recent progress in understanding the structure-function relationships of the insulin and insulin-like growth factor 1 (IGF1) receptors, their mechanism of activation and their implications for the design of insulin-receptor agonists for diabetes therapy and IGF1-receptor antagonists for cancer therapy. |
| 537 | 12387452 | We have previously suggested that alterations in sequential early gene responses of trophic factors (IGF-1 -->c-fos-->NGF) contribute to impaired peripheral nerve regeneration in type 1 diabetic BB/W-rats. |
| 538 | 12387452 | The expression of IGF-1, c-fos, NGF and the receptors p75 and IGF-1R were determined at the protein and mRNA levels in sciatic nerve distal to the crush site by immunoblotting and semi-quantitative RT-PCR. |
| 539 | 12387452 | In situ hybridization was performed to assess the cellular localization of IGF-1, NGF, p75, and IGF-1R mRNA and immunohistochemistry served to localize the source of p75 and IGF-1R protein expression. |
| 540 | 12387452 | IGF-1R was expressed in Schwann cells and its expression was asynchronous to IGF-1 expression in type 1 rats but remained synchronous with IGF-1 in control and type 2 animals. |
| 541 | 12387452 | We have previously suggested that alterations in sequential early gene responses of trophic factors (IGF-1 -->c-fos-->NGF) contribute to impaired peripheral nerve regeneration in type 1 diabetic BB/W-rats. |
| 542 | 12387452 | The expression of IGF-1, c-fos, NGF and the receptors p75 and IGF-1R were determined at the protein and mRNA levels in sciatic nerve distal to the crush site by immunoblotting and semi-quantitative RT-PCR. |
| 543 | 12387452 | In situ hybridization was performed to assess the cellular localization of IGF-1, NGF, p75, and IGF-1R mRNA and immunohistochemistry served to localize the source of p75 and IGF-1R protein expression. |
| 544 | 12387452 | IGF-1R was expressed in Schwann cells and its expression was asynchronous to IGF-1 expression in type 1 rats but remained synchronous with IGF-1 in control and type 2 animals. |
| 545 | 12387452 | We have previously suggested that alterations in sequential early gene responses of trophic factors (IGF-1 -->c-fos-->NGF) contribute to impaired peripheral nerve regeneration in type 1 diabetic BB/W-rats. |
| 546 | 12387452 | The expression of IGF-1, c-fos, NGF and the receptors p75 and IGF-1R were determined at the protein and mRNA levels in sciatic nerve distal to the crush site by immunoblotting and semi-quantitative RT-PCR. |
| 547 | 12387452 | In situ hybridization was performed to assess the cellular localization of IGF-1, NGF, p75, and IGF-1R mRNA and immunohistochemistry served to localize the source of p75 and IGF-1R protein expression. |
| 548 | 12387452 | IGF-1R was expressed in Schwann cells and its expression was asynchronous to IGF-1 expression in type 1 rats but remained synchronous with IGF-1 in control and type 2 animals. |
| 549 | 12438247 | Reduced expression of insulin-like growth factor I receptors in MCF-7 breast cancer cells leads to a more metastatic phenotype. |
| 550 | 12438247 | Several lines of evidence support an important role for the insulin-like growth factor system in breast cancer. |
| 551 | 12438247 | Alterations in insulin-like growth factor I receptor (IGF-IR) have been associated with breast cancer metastasis; however, the specific role played by the IGF-IR in this process remains unclear. |
| 552 | 12438247 | Moreover, there was a significant reduction in p120 present in the E-cadherin-catenin-p120 complex. |
| 553 | 12438247 | There was a 2-fold increase in active Rac1 and Cdc42 and a 35% decrease in active Rho in the SX13 cells. |
| 554 | 12438247 | Our findings strongly suggest that the IGF-IR plays a role in the stabilization of the E-cadherin-catenin complex, thereby providing one possible explanation for the association between low levels of IGF-IR and a higher risk of mammary tumor metastasis. |
| 555 | 12438247 | Reduced expression of insulin-like growth factor I receptors in MCF-7 breast cancer cells leads to a more metastatic phenotype. |
| 556 | 12438247 | Several lines of evidence support an important role for the insulin-like growth factor system in breast cancer. |
| 557 | 12438247 | Alterations in insulin-like growth factor I receptor (IGF-IR) have been associated with breast cancer metastasis; however, the specific role played by the IGF-IR in this process remains unclear. |
| 558 | 12438247 | Moreover, there was a significant reduction in p120 present in the E-cadherin-catenin-p120 complex. |
| 559 | 12438247 | There was a 2-fold increase in active Rac1 and Cdc42 and a 35% decrease in active Rho in the SX13 cells. |
| 560 | 12438247 | Our findings strongly suggest that the IGF-IR plays a role in the stabilization of the E-cadherin-catenin complex, thereby providing one possible explanation for the association between low levels of IGF-IR and a higher risk of mammary tumor metastasis. |
| 561 | 12577314 | Glomerular mesangial cells both synthesize and respond to insulin-like growth factor-1 (IGF-1). |
| 562 | 12577314 | We have reported that primary glomerular mesangial cells derived from SPARC-null mice exhibit an accelerated rate of proliferation and produce substantially decreased levels of transforming growth factor beta1 (TGF-beta1) in comparison to their wild-type counterparts (Francki et al. [1999] J. |
| 563 | 12577314 | SPARC-null mesangial cells produce increased amounts of IGF-1 and -2, as well as IGF-1 receptor (IGF-1R) in comparison to wild-type cells. |
| 564 | 12577314 | Addition of recombinant SPARC to SPARC-null cells inhibited IGF-1-stimulated mitogen activated protein kinase (MAPK) activation and DNA synthesis. |
| 565 | 12577314 | We also show that the observed accelerated rate of basal and IGF-1-stimulated proliferation in mesangial cells derived from SPARC-null animals is due, at least in part, to markedly diminished levels of cyclin D1 and the cyclin-dependent kinase (cdk) inhibitors p21 and p27. |
| 566 | 12604504 | At present, the circulating bioactivity of insulin-like growth factor I (IGF-I) is estimated by immunological measurements of IGF-I levels. |
| 567 | 12604504 | However, immunoassays ignore the modifying effects of the IGF-binding proteins (IGFBPs) on the interaction between IGF-I and the IGF-I receptor (IGF-IR). |
| 568 | 12604504 | Therefore, we developed an IGF-I kinase receptor activation assay (KIRA) based on cells transfected with the human IGF-IR gene. |
| 569 | 12604504 | The bioassay was sensitive (detection limit 0.08 microg/l), specific (cross-reactivity of insulin, insulin analogs, and proinsulin was <1%; IGF-II cross-reactivity was 12%), and accurate (within- and between-assay coefficients of variation <7 and <15%). |
| 570 | 12604504 | Addition of IGFBPs dose dependently reduced the KIRA signal, whereas addition of IGF-II to preformed complexes (1:1 molar ratio) of IGF-I and IGFBP dose dependently increased IGF-I bioactivity by displacement of bound IGF-I. |
| 571 | 12604504 | At present, the circulating bioactivity of insulin-like growth factor I (IGF-I) is estimated by immunological measurements of IGF-I levels. |
| 572 | 12604504 | However, immunoassays ignore the modifying effects of the IGF-binding proteins (IGFBPs) on the interaction between IGF-I and the IGF-I receptor (IGF-IR). |
| 573 | 12604504 | Therefore, we developed an IGF-I kinase receptor activation assay (KIRA) based on cells transfected with the human IGF-IR gene. |
| 574 | 12604504 | The bioassay was sensitive (detection limit 0.08 microg/l), specific (cross-reactivity of insulin, insulin analogs, and proinsulin was <1%; IGF-II cross-reactivity was 12%), and accurate (within- and between-assay coefficients of variation <7 and <15%). |
| 575 | 12604504 | Addition of IGFBPs dose dependently reduced the KIRA signal, whereas addition of IGF-II to preformed complexes (1:1 molar ratio) of IGF-I and IGFBP dose dependently increased IGF-I bioactivity by displacement of bound IGF-I. |
| 576 | 12867429 | The cyclin-dependent kinase inhibitor p21CIP/WAF is a positive regulator of insulin-like growth factor I-induced cell proliferation in MCF-7 human breast cancer cells. |
| 577 | 12867429 | This IGF-1 effect was reduced by 50% in MCF-7-derived cells (SX13), which exhibit a 50% reduction in IGF-1R expression, demonstrating that IGF-1 receptor activation was involved in this process. |
| 578 | 12867429 | Preincubation with the ERK1/2 inhibitor U0126 significantly reduced the IGF-1 effect on the amount of p21CIP/WAF protein in MCF-7 cells. |
| 579 | 12867429 | These results were confirmed by the expression of a dominant negative construct for MEK-1 suggesting that the increase of the abundance of p21CIP/WAF in response to IGF-1 occurs via the ERK1/2 mitogen-activated protein kinase pathway. |
| 580 | 12867429 | This latter result is explained by a delay in G1 to S cell cycle progression due partly to a reduction in the activation of some components of cell cycle including the induction of cyclin D1 expression in response to IGF-1. |
| 581 | 12867429 | MCF-7 cells transiently overexpressing p21 showed increased basal and IGF-I-induced thymidine incorporation. |
| 582 | 12960377 | Stearoyl-CoA desaturase 1 deficiency elevates insulin-signaling components and down-regulates protein-tyrosine phosphatase 1B in muscle. |
| 583 | 12960377 | We have shown previously that mice with a targeted disruption in the stearoyl-CoA desaturase 1 gene (SCD1-/-) have increased insulin sensitivity compared with control mice. |
| 584 | 12960377 | Here we show that the SCD1-/- mice have increased insulin signaling in muscle. |
| 585 | 12960377 | The tyrosine phosphorylation of insulin-like growth factor-1 receptor was similar between SCD1+/+ and SCD1-/- mice. |
| 586 | 12960377 | The association of insulin receptor substrates 1 and 2 with alphap85 subunit of phosphatidylinositol 3-kinase as well as the phosphorylation of Akt-Ser-473 and Akt-Thr-308 are also elevated in the SCD1-/- mice. |
| 587 | 12960377 | Interestingly, the mRNA levels, protein mass, and activity of the protein-tyrosine phosphatase-1B implicated in the attenuation of the insulin signal are reduced in the SCD1-/- mice, whereas the levels of the leukocyte antigen-related protein phosphatase are similar between two groups of mice. |
| 588 | 12960377 | The content of glucose transporter 4 in the plasma membrane and basal as well as insulin-mediated glucose uptake are increased in the SCD1-/- mice. |
| 589 | 12960377 | We hypothesize that loss of SCD1 function induces increased insulin signaling at least in part by a reduction in the expression of protein-tyrosine phosphatase 1B. |
| 590 | 12970367 | Hsp10 and Hsp60 suppress ubiquitination of insulin-like growth factor-1 receptor and augment insulin-like growth factor-1 receptor signaling in cardiac muscle: implications on decreased myocardial protection in diabetic cardiomyopathy. |
| 591 | 12970367 | We have investigated the effects of two heat shock proteins, Hsp10 and Hsp60, on insulin-like growth factor-1 receptor (IGF-1R) signaling in cardiac muscle cells. |
| 592 | 12970367 | Neonatal cardiomyocytes were transduced with Hsp10 or Hsp60 via adenoviral vector. |
| 593 | 12970367 | Compared with the cells transduced with a control vector, overexpression of Hsp10 or Hsp60 increased the abundance of IGF-1R and IGF-1-stimulated receptor autophosphorylation. |
| 594 | 12970367 | Thus, Hsp10 and Hsp60 overexpression increased the number of functioning receptors and amplified activation of IGF-1R signaling. |
| 595 | 12970367 | IGF-1 stimulation of MEK, Erk, p90Rsk, and Akt were accordingly augmented. |
| 596 | 12970367 | Transducing cardiomyocytes with antisense Hsp60 oligonucleotides reduced Hsp60 expression, decreased the abundance of IGF-1R, attenuated IGF-1R autophosphorylation, and suppressed the pro-survival action of IGF-1 in cardiomyocytes. |
| 597 | 12970367 | Using cycloheximide to inhibit protein synthesis did not alter the effect of Hsp60 on IGF-1R signaling, and IGF-1R mRNA levels were not up-regulated by Hsp10 or Hsp60. |
| 598 | 12970367 | Additional experiments showed that Hsp10 and Hsp60 suppressed polyubiquitination of IGF-1 receptor. |
| 599 | 12970367 | These data indicate that Hsp10 and Hsp60 can modulate IGF-1R signaling through post-translational modification. |
| 600 | 12970367 | In animal models of diabetes, diabetic myocardium is associated with decreased abundance of Hsp60, increased ubiquitination of IGF-1R, and lower level of IGF-1R protein. |
| 601 | 12970367 | These data suggest that decreased Hsp60 expression and subsequent decline of IGF-1R signaling may be a fundamental mechanism underlying the development of diabetic cardiomyopathy. |
| 602 | 12970367 | Hsp10 and Hsp60 suppress ubiquitination of insulin-like growth factor-1 receptor and augment insulin-like growth factor-1 receptor signaling in cardiac muscle: implications on decreased myocardial protection in diabetic cardiomyopathy. |
| 603 | 12970367 | We have investigated the effects of two heat shock proteins, Hsp10 and Hsp60, on insulin-like growth factor-1 receptor (IGF-1R) signaling in cardiac muscle cells. |
| 604 | 12970367 | Neonatal cardiomyocytes were transduced with Hsp10 or Hsp60 via adenoviral vector. |
| 605 | 12970367 | Compared with the cells transduced with a control vector, overexpression of Hsp10 or Hsp60 increased the abundance of IGF-1R and IGF-1-stimulated receptor autophosphorylation. |
| 606 | 12970367 | Thus, Hsp10 and Hsp60 overexpression increased the number of functioning receptors and amplified activation of IGF-1R signaling. |
| 607 | 12970367 | IGF-1 stimulation of MEK, Erk, p90Rsk, and Akt were accordingly augmented. |
| 608 | 12970367 | Transducing cardiomyocytes with antisense Hsp60 oligonucleotides reduced Hsp60 expression, decreased the abundance of IGF-1R, attenuated IGF-1R autophosphorylation, and suppressed the pro-survival action of IGF-1 in cardiomyocytes. |
| 609 | 12970367 | Using cycloheximide to inhibit protein synthesis did not alter the effect of Hsp60 on IGF-1R signaling, and IGF-1R mRNA levels were not up-regulated by Hsp10 or Hsp60. |
| 610 | 12970367 | Additional experiments showed that Hsp10 and Hsp60 suppressed polyubiquitination of IGF-1 receptor. |
| 611 | 12970367 | These data indicate that Hsp10 and Hsp60 can modulate IGF-1R signaling through post-translational modification. |
| 612 | 12970367 | In animal models of diabetes, diabetic myocardium is associated with decreased abundance of Hsp60, increased ubiquitination of IGF-1R, and lower level of IGF-1R protein. |
| 613 | 12970367 | These data suggest that decreased Hsp60 expression and subsequent decline of IGF-1R signaling may be a fundamental mechanism underlying the development of diabetic cardiomyopathy. |
| 614 | 12970367 | Hsp10 and Hsp60 suppress ubiquitination of insulin-like growth factor-1 receptor and augment insulin-like growth factor-1 receptor signaling in cardiac muscle: implications on decreased myocardial protection in diabetic cardiomyopathy. |
| 615 | 12970367 | We have investigated the effects of two heat shock proteins, Hsp10 and Hsp60, on insulin-like growth factor-1 receptor (IGF-1R) signaling in cardiac muscle cells. |
| 616 | 12970367 | Neonatal cardiomyocytes were transduced with Hsp10 or Hsp60 via adenoviral vector. |
| 617 | 12970367 | Compared with the cells transduced with a control vector, overexpression of Hsp10 or Hsp60 increased the abundance of IGF-1R and IGF-1-stimulated receptor autophosphorylation. |
| 618 | 12970367 | Thus, Hsp10 and Hsp60 overexpression increased the number of functioning receptors and amplified activation of IGF-1R signaling. |
| 619 | 12970367 | IGF-1 stimulation of MEK, Erk, p90Rsk, and Akt were accordingly augmented. |
| 620 | 12970367 | Transducing cardiomyocytes with antisense Hsp60 oligonucleotides reduced Hsp60 expression, decreased the abundance of IGF-1R, attenuated IGF-1R autophosphorylation, and suppressed the pro-survival action of IGF-1 in cardiomyocytes. |
| 621 | 12970367 | Using cycloheximide to inhibit protein synthesis did not alter the effect of Hsp60 on IGF-1R signaling, and IGF-1R mRNA levels were not up-regulated by Hsp10 or Hsp60. |
| 622 | 12970367 | Additional experiments showed that Hsp10 and Hsp60 suppressed polyubiquitination of IGF-1 receptor. |
| 623 | 12970367 | These data indicate that Hsp10 and Hsp60 can modulate IGF-1R signaling through post-translational modification. |
| 624 | 12970367 | In animal models of diabetes, diabetic myocardium is associated with decreased abundance of Hsp60, increased ubiquitination of IGF-1R, and lower level of IGF-1R protein. |
| 625 | 12970367 | These data suggest that decreased Hsp60 expression and subsequent decline of IGF-1R signaling may be a fundamental mechanism underlying the development of diabetic cardiomyopathy. |
| 626 | 12970367 | Hsp10 and Hsp60 suppress ubiquitination of insulin-like growth factor-1 receptor and augment insulin-like growth factor-1 receptor signaling in cardiac muscle: implications on decreased myocardial protection in diabetic cardiomyopathy. |
| 627 | 12970367 | We have investigated the effects of two heat shock proteins, Hsp10 and Hsp60, on insulin-like growth factor-1 receptor (IGF-1R) signaling in cardiac muscle cells. |
| 628 | 12970367 | Neonatal cardiomyocytes were transduced with Hsp10 or Hsp60 via adenoviral vector. |
| 629 | 12970367 | Compared with the cells transduced with a control vector, overexpression of Hsp10 or Hsp60 increased the abundance of IGF-1R and IGF-1-stimulated receptor autophosphorylation. |
| 630 | 12970367 | Thus, Hsp10 and Hsp60 overexpression increased the number of functioning receptors and amplified activation of IGF-1R signaling. |
| 631 | 12970367 | IGF-1 stimulation of MEK, Erk, p90Rsk, and Akt were accordingly augmented. |
| 632 | 12970367 | Transducing cardiomyocytes with antisense Hsp60 oligonucleotides reduced Hsp60 expression, decreased the abundance of IGF-1R, attenuated IGF-1R autophosphorylation, and suppressed the pro-survival action of IGF-1 in cardiomyocytes. |
| 633 | 12970367 | Using cycloheximide to inhibit protein synthesis did not alter the effect of Hsp60 on IGF-1R signaling, and IGF-1R mRNA levels were not up-regulated by Hsp10 or Hsp60. |
| 634 | 12970367 | Additional experiments showed that Hsp10 and Hsp60 suppressed polyubiquitination of IGF-1 receptor. |
| 635 | 12970367 | These data indicate that Hsp10 and Hsp60 can modulate IGF-1R signaling through post-translational modification. |
| 636 | 12970367 | In animal models of diabetes, diabetic myocardium is associated with decreased abundance of Hsp60, increased ubiquitination of IGF-1R, and lower level of IGF-1R protein. |
| 637 | 12970367 | These data suggest that decreased Hsp60 expression and subsequent decline of IGF-1R signaling may be a fundamental mechanism underlying the development of diabetic cardiomyopathy. |
| 638 | 12970367 | Hsp10 and Hsp60 suppress ubiquitination of insulin-like growth factor-1 receptor and augment insulin-like growth factor-1 receptor signaling in cardiac muscle: implications on decreased myocardial protection in diabetic cardiomyopathy. |
| 639 | 12970367 | We have investigated the effects of two heat shock proteins, Hsp10 and Hsp60, on insulin-like growth factor-1 receptor (IGF-1R) signaling in cardiac muscle cells. |
| 640 | 12970367 | Neonatal cardiomyocytes were transduced with Hsp10 or Hsp60 via adenoviral vector. |
| 641 | 12970367 | Compared with the cells transduced with a control vector, overexpression of Hsp10 or Hsp60 increased the abundance of IGF-1R and IGF-1-stimulated receptor autophosphorylation. |
| 642 | 12970367 | Thus, Hsp10 and Hsp60 overexpression increased the number of functioning receptors and amplified activation of IGF-1R signaling. |
| 643 | 12970367 | IGF-1 stimulation of MEK, Erk, p90Rsk, and Akt were accordingly augmented. |
| 644 | 12970367 | Transducing cardiomyocytes with antisense Hsp60 oligonucleotides reduced Hsp60 expression, decreased the abundance of IGF-1R, attenuated IGF-1R autophosphorylation, and suppressed the pro-survival action of IGF-1 in cardiomyocytes. |
| 645 | 12970367 | Using cycloheximide to inhibit protein synthesis did not alter the effect of Hsp60 on IGF-1R signaling, and IGF-1R mRNA levels were not up-regulated by Hsp10 or Hsp60. |
| 646 | 12970367 | Additional experiments showed that Hsp10 and Hsp60 suppressed polyubiquitination of IGF-1 receptor. |
| 647 | 12970367 | These data indicate that Hsp10 and Hsp60 can modulate IGF-1R signaling through post-translational modification. |
| 648 | 12970367 | In animal models of diabetes, diabetic myocardium is associated with decreased abundance of Hsp60, increased ubiquitination of IGF-1R, and lower level of IGF-1R protein. |
| 649 | 12970367 | These data suggest that decreased Hsp60 expression and subsequent decline of IGF-1R signaling may be a fundamental mechanism underlying the development of diabetic cardiomyopathy. |
| 650 | 12970367 | Hsp10 and Hsp60 suppress ubiquitination of insulin-like growth factor-1 receptor and augment insulin-like growth factor-1 receptor signaling in cardiac muscle: implications on decreased myocardial protection in diabetic cardiomyopathy. |
| 651 | 12970367 | We have investigated the effects of two heat shock proteins, Hsp10 and Hsp60, on insulin-like growth factor-1 receptor (IGF-1R) signaling in cardiac muscle cells. |
| 652 | 12970367 | Neonatal cardiomyocytes were transduced with Hsp10 or Hsp60 via adenoviral vector. |
| 653 | 12970367 | Compared with the cells transduced with a control vector, overexpression of Hsp10 or Hsp60 increased the abundance of IGF-1R and IGF-1-stimulated receptor autophosphorylation. |
| 654 | 12970367 | Thus, Hsp10 and Hsp60 overexpression increased the number of functioning receptors and amplified activation of IGF-1R signaling. |
| 655 | 12970367 | IGF-1 stimulation of MEK, Erk, p90Rsk, and Akt were accordingly augmented. |
| 656 | 12970367 | Transducing cardiomyocytes with antisense Hsp60 oligonucleotides reduced Hsp60 expression, decreased the abundance of IGF-1R, attenuated IGF-1R autophosphorylation, and suppressed the pro-survival action of IGF-1 in cardiomyocytes. |
| 657 | 12970367 | Using cycloheximide to inhibit protein synthesis did not alter the effect of Hsp60 on IGF-1R signaling, and IGF-1R mRNA levels were not up-regulated by Hsp10 or Hsp60. |
| 658 | 12970367 | Additional experiments showed that Hsp10 and Hsp60 suppressed polyubiquitination of IGF-1 receptor. |
| 659 | 12970367 | These data indicate that Hsp10 and Hsp60 can modulate IGF-1R signaling through post-translational modification. |
| 660 | 12970367 | In animal models of diabetes, diabetic myocardium is associated with decreased abundance of Hsp60, increased ubiquitination of IGF-1R, and lower level of IGF-1R protein. |
| 661 | 12970367 | These data suggest that decreased Hsp60 expression and subsequent decline of IGF-1R signaling may be a fundamental mechanism underlying the development of diabetic cardiomyopathy. |
| 662 | 12970367 | Hsp10 and Hsp60 suppress ubiquitination of insulin-like growth factor-1 receptor and augment insulin-like growth factor-1 receptor signaling in cardiac muscle: implications on decreased myocardial protection in diabetic cardiomyopathy. |
| 663 | 12970367 | We have investigated the effects of two heat shock proteins, Hsp10 and Hsp60, on insulin-like growth factor-1 receptor (IGF-1R) signaling in cardiac muscle cells. |
| 664 | 12970367 | Neonatal cardiomyocytes were transduced with Hsp10 or Hsp60 via adenoviral vector. |
| 665 | 12970367 | Compared with the cells transduced with a control vector, overexpression of Hsp10 or Hsp60 increased the abundance of IGF-1R and IGF-1-stimulated receptor autophosphorylation. |
| 666 | 12970367 | Thus, Hsp10 and Hsp60 overexpression increased the number of functioning receptors and amplified activation of IGF-1R signaling. |
| 667 | 12970367 | IGF-1 stimulation of MEK, Erk, p90Rsk, and Akt were accordingly augmented. |
| 668 | 12970367 | Transducing cardiomyocytes with antisense Hsp60 oligonucleotides reduced Hsp60 expression, decreased the abundance of IGF-1R, attenuated IGF-1R autophosphorylation, and suppressed the pro-survival action of IGF-1 in cardiomyocytes. |
| 669 | 12970367 | Using cycloheximide to inhibit protein synthesis did not alter the effect of Hsp60 on IGF-1R signaling, and IGF-1R mRNA levels were not up-regulated by Hsp10 or Hsp60. |
| 670 | 12970367 | Additional experiments showed that Hsp10 and Hsp60 suppressed polyubiquitination of IGF-1 receptor. |
| 671 | 12970367 | These data indicate that Hsp10 and Hsp60 can modulate IGF-1R signaling through post-translational modification. |
| 672 | 12970367 | In animal models of diabetes, diabetic myocardium is associated with decreased abundance of Hsp60, increased ubiquitination of IGF-1R, and lower level of IGF-1R protein. |
| 673 | 12970367 | These data suggest that decreased Hsp60 expression and subsequent decline of IGF-1R signaling may be a fundamental mechanism underlying the development of diabetic cardiomyopathy. |
| 674 | 12970367 | Hsp10 and Hsp60 suppress ubiquitination of insulin-like growth factor-1 receptor and augment insulin-like growth factor-1 receptor signaling in cardiac muscle: implications on decreased myocardial protection in diabetic cardiomyopathy. |
| 675 | 12970367 | We have investigated the effects of two heat shock proteins, Hsp10 and Hsp60, on insulin-like growth factor-1 receptor (IGF-1R) signaling in cardiac muscle cells. |
| 676 | 12970367 | Neonatal cardiomyocytes were transduced with Hsp10 or Hsp60 via adenoviral vector. |
| 677 | 12970367 | Compared with the cells transduced with a control vector, overexpression of Hsp10 or Hsp60 increased the abundance of IGF-1R and IGF-1-stimulated receptor autophosphorylation. |
| 678 | 12970367 | Thus, Hsp10 and Hsp60 overexpression increased the number of functioning receptors and amplified activation of IGF-1R signaling. |
| 679 | 12970367 | IGF-1 stimulation of MEK, Erk, p90Rsk, and Akt were accordingly augmented. |
| 680 | 12970367 | Transducing cardiomyocytes with antisense Hsp60 oligonucleotides reduced Hsp60 expression, decreased the abundance of IGF-1R, attenuated IGF-1R autophosphorylation, and suppressed the pro-survival action of IGF-1 in cardiomyocytes. |
| 681 | 12970367 | Using cycloheximide to inhibit protein synthesis did not alter the effect of Hsp60 on IGF-1R signaling, and IGF-1R mRNA levels were not up-regulated by Hsp10 or Hsp60. |
| 682 | 12970367 | Additional experiments showed that Hsp10 and Hsp60 suppressed polyubiquitination of IGF-1 receptor. |
| 683 | 12970367 | These data indicate that Hsp10 and Hsp60 can modulate IGF-1R signaling through post-translational modification. |
| 684 | 12970367 | In animal models of diabetes, diabetic myocardium is associated with decreased abundance of Hsp60, increased ubiquitination of IGF-1R, and lower level of IGF-1R protein. |
| 685 | 12970367 | These data suggest that decreased Hsp60 expression and subsequent decline of IGF-1R signaling may be a fundamental mechanism underlying the development of diabetic cardiomyopathy. |
| 686 | 12970367 | Hsp10 and Hsp60 suppress ubiquitination of insulin-like growth factor-1 receptor and augment insulin-like growth factor-1 receptor signaling in cardiac muscle: implications on decreased myocardial protection in diabetic cardiomyopathy. |
| 687 | 12970367 | We have investigated the effects of two heat shock proteins, Hsp10 and Hsp60, on insulin-like growth factor-1 receptor (IGF-1R) signaling in cardiac muscle cells. |
| 688 | 12970367 | Neonatal cardiomyocytes were transduced with Hsp10 or Hsp60 via adenoviral vector. |
| 689 | 12970367 | Compared with the cells transduced with a control vector, overexpression of Hsp10 or Hsp60 increased the abundance of IGF-1R and IGF-1-stimulated receptor autophosphorylation. |
| 690 | 12970367 | Thus, Hsp10 and Hsp60 overexpression increased the number of functioning receptors and amplified activation of IGF-1R signaling. |
| 691 | 12970367 | IGF-1 stimulation of MEK, Erk, p90Rsk, and Akt were accordingly augmented. |
| 692 | 12970367 | Transducing cardiomyocytes with antisense Hsp60 oligonucleotides reduced Hsp60 expression, decreased the abundance of IGF-1R, attenuated IGF-1R autophosphorylation, and suppressed the pro-survival action of IGF-1 in cardiomyocytes. |
| 693 | 12970367 | Using cycloheximide to inhibit protein synthesis did not alter the effect of Hsp60 on IGF-1R signaling, and IGF-1R mRNA levels were not up-regulated by Hsp10 or Hsp60. |
| 694 | 12970367 | Additional experiments showed that Hsp10 and Hsp60 suppressed polyubiquitination of IGF-1 receptor. |
| 695 | 12970367 | These data indicate that Hsp10 and Hsp60 can modulate IGF-1R signaling through post-translational modification. |
| 696 | 12970367 | In animal models of diabetes, diabetic myocardium is associated with decreased abundance of Hsp60, increased ubiquitination of IGF-1R, and lower level of IGF-1R protein. |
| 697 | 12970367 | These data suggest that decreased Hsp60 expression and subsequent decline of IGF-1R signaling may be a fundamental mechanism underlying the development of diabetic cardiomyopathy. |
| 698 | 14604834 | Expression, regulation, and function of IGF-1, IGF-1R, and IGF-1 binding proteins in blood vessels. |
| 699 | 14604834 | The vascular insulin-like growth factor (IGF)-1 system includes the IGFs, the IGF-1 receptor (IGF-1R), and multiple binding proteins. |
| 700 | 14604834 | The effects of IGF-1 are mediated principally through the IGF-1R but are modulated by complex interactions with multiple IGF binding proteins that themselves are regulated by phosphorylation, proteolysis, polymerization, and cell or matrix association. |
| 701 | 14604834 | This review will discuss the regulation of expression of IGF-1, IGF-1R, and IGF binding proteins in the vasculature and summarize evidence implicating involvement of this system in vascular diseases. |
| 702 | 14604834 | Expression, regulation, and function of IGF-1, IGF-1R, and IGF-1 binding proteins in blood vessels. |
| 703 | 14604834 | The vascular insulin-like growth factor (IGF)-1 system includes the IGFs, the IGF-1 receptor (IGF-1R), and multiple binding proteins. |
| 704 | 14604834 | The effects of IGF-1 are mediated principally through the IGF-1R but are modulated by complex interactions with multiple IGF binding proteins that themselves are regulated by phosphorylation, proteolysis, polymerization, and cell or matrix association. |
| 705 | 14604834 | This review will discuss the regulation of expression of IGF-1, IGF-1R, and IGF binding proteins in the vasculature and summarize evidence implicating involvement of this system in vascular diseases. |
| 706 | 14604834 | Expression, regulation, and function of IGF-1, IGF-1R, and IGF-1 binding proteins in blood vessels. |
| 707 | 14604834 | The vascular insulin-like growth factor (IGF)-1 system includes the IGFs, the IGF-1 receptor (IGF-1R), and multiple binding proteins. |
| 708 | 14604834 | The effects of IGF-1 are mediated principally through the IGF-1R but are modulated by complex interactions with multiple IGF binding proteins that themselves are regulated by phosphorylation, proteolysis, polymerization, and cell or matrix association. |
| 709 | 14604834 | This review will discuss the regulation of expression of IGF-1, IGF-1R, and IGF binding proteins in the vasculature and summarize evidence implicating involvement of this system in vascular diseases. |
| 710 | 14604834 | Expression, regulation, and function of IGF-1, IGF-1R, and IGF-1 binding proteins in blood vessels. |
| 711 | 14604834 | The vascular insulin-like growth factor (IGF)-1 system includes the IGFs, the IGF-1 receptor (IGF-1R), and multiple binding proteins. |
| 712 | 14604834 | The effects of IGF-1 are mediated principally through the IGF-1R but are modulated by complex interactions with multiple IGF binding proteins that themselves are regulated by phosphorylation, proteolysis, polymerization, and cell or matrix association. |
| 713 | 14604834 | This review will discuss the regulation of expression of IGF-1, IGF-1R, and IGF binding proteins in the vasculature and summarize evidence implicating involvement of this system in vascular diseases. |
| 714 | 14604996 | Role of insulin receptor substrates and protein kinase C-zeta in vascular permeability factor/vascular endothelial growth factor expression in pancreatic cancer cells. |
| 715 | 14604996 | Previously we have shown that in AsPC-1 pancreatic adenocarcinoma cells, insulin-like growth factor receptor (IGF-IR) regulates VPF/VEGF expression. |
| 716 | 14604996 | Insulin receptor substrate-1 and -2 (IRS-1 and IRS-2), two major downstream molecules of IGF-1R, are known to be important in the genesis of diabetes. |
| 717 | 14604996 | The Sp1-dependent VPF/VEGF transcription is regulated mainly by IRS-2. |
| 718 | 14604996 | Protein kinase C-zeta (PKC-zeta) plays a central role in VPF/VEGF expression and acts as a switching element. |
| 719 | 14604996 | Furthermore, we have also demonstrated that the phosphatidylinositol 3-kinase pathway, but not the Ras pathway, is a downstream event of IRS proteins for VPF/VEGF expression in AsPC-1 cells. |
| 720 | 14604996 | Interestingly, like renal cancer cells, in AsPC-1 cells PKC-zeta leads to direct Sp1-dependent VPF/VEGF transcription; in addition, it also promotes a negative feedback loop to IRS-2 that decreases the association of IRS-2/IGF-1R and IRS-2/p85. |
| 721 | 14604996 | Taken together, our results show that in AsPC-1 pancreatic carcinoma cells, Sp1-dependent VPF/VEGF transcription is controlled by IGF-1R signaling through IRS-2 proteins and modulated by a negative feedback loop of PKC-zeta to IRS-2. |
| 722 | 14604996 | Role of insulin receptor substrates and protein kinase C-zeta in vascular permeability factor/vascular endothelial growth factor expression in pancreatic cancer cells. |
| 723 | 14604996 | Previously we have shown that in AsPC-1 pancreatic adenocarcinoma cells, insulin-like growth factor receptor (IGF-IR) regulates VPF/VEGF expression. |
| 724 | 14604996 | Insulin receptor substrate-1 and -2 (IRS-1 and IRS-2), two major downstream molecules of IGF-1R, are known to be important in the genesis of diabetes. |
| 725 | 14604996 | The Sp1-dependent VPF/VEGF transcription is regulated mainly by IRS-2. |
| 726 | 14604996 | Protein kinase C-zeta (PKC-zeta) plays a central role in VPF/VEGF expression and acts as a switching element. |
| 727 | 14604996 | Furthermore, we have also demonstrated that the phosphatidylinositol 3-kinase pathway, but not the Ras pathway, is a downstream event of IRS proteins for VPF/VEGF expression in AsPC-1 cells. |
| 728 | 14604996 | Interestingly, like renal cancer cells, in AsPC-1 cells PKC-zeta leads to direct Sp1-dependent VPF/VEGF transcription; in addition, it also promotes a negative feedback loop to IRS-2 that decreases the association of IRS-2/IGF-1R and IRS-2/p85. |
| 729 | 14604996 | Taken together, our results show that in AsPC-1 pancreatic carcinoma cells, Sp1-dependent VPF/VEGF transcription is controlled by IGF-1R signaling through IRS-2 proteins and modulated by a negative feedback loop of PKC-zeta to IRS-2. |
| 730 | 14604996 | Role of insulin receptor substrates and protein kinase C-zeta in vascular permeability factor/vascular endothelial growth factor expression in pancreatic cancer cells. |
| 731 | 14604996 | Previously we have shown that in AsPC-1 pancreatic adenocarcinoma cells, insulin-like growth factor receptor (IGF-IR) regulates VPF/VEGF expression. |
| 732 | 14604996 | Insulin receptor substrate-1 and -2 (IRS-1 and IRS-2), two major downstream molecules of IGF-1R, are known to be important in the genesis of diabetes. |
| 733 | 14604996 | The Sp1-dependent VPF/VEGF transcription is regulated mainly by IRS-2. |
| 734 | 14604996 | Protein kinase C-zeta (PKC-zeta) plays a central role in VPF/VEGF expression and acts as a switching element. |
| 735 | 14604996 | Furthermore, we have also demonstrated that the phosphatidylinositol 3-kinase pathway, but not the Ras pathway, is a downstream event of IRS proteins for VPF/VEGF expression in AsPC-1 cells. |
| 736 | 14604996 | Interestingly, like renal cancer cells, in AsPC-1 cells PKC-zeta leads to direct Sp1-dependent VPF/VEGF transcription; in addition, it also promotes a negative feedback loop to IRS-2 that decreases the association of IRS-2/IGF-1R and IRS-2/p85. |
| 737 | 14604996 | Taken together, our results show that in AsPC-1 pancreatic carcinoma cells, Sp1-dependent VPF/VEGF transcription is controlled by IGF-1R signaling through IRS-2 proteins and modulated by a negative feedback loop of PKC-zeta to IRS-2. |
| 738 | 14604996 | Role of insulin receptor substrates and protein kinase C-zeta in vascular permeability factor/vascular endothelial growth factor expression in pancreatic cancer cells. |
| 739 | 14604996 | Previously we have shown that in AsPC-1 pancreatic adenocarcinoma cells, insulin-like growth factor receptor (IGF-IR) regulates VPF/VEGF expression. |
| 740 | 14604996 | Insulin receptor substrate-1 and -2 (IRS-1 and IRS-2), two major downstream molecules of IGF-1R, are known to be important in the genesis of diabetes. |
| 741 | 14604996 | The Sp1-dependent VPF/VEGF transcription is regulated mainly by IRS-2. |
| 742 | 14604996 | Protein kinase C-zeta (PKC-zeta) plays a central role in VPF/VEGF expression and acts as a switching element. |
| 743 | 14604996 | Furthermore, we have also demonstrated that the phosphatidylinositol 3-kinase pathway, but not the Ras pathway, is a downstream event of IRS proteins for VPF/VEGF expression in AsPC-1 cells. |
| 744 | 14604996 | Interestingly, like renal cancer cells, in AsPC-1 cells PKC-zeta leads to direct Sp1-dependent VPF/VEGF transcription; in addition, it also promotes a negative feedback loop to IRS-2 that decreases the association of IRS-2/IGF-1R and IRS-2/p85. |
| 745 | 14604996 | Taken together, our results show that in AsPC-1 pancreatic carcinoma cells, Sp1-dependent VPF/VEGF transcription is controlled by IGF-1R signaling through IRS-2 proteins and modulated by a negative feedback loop of PKC-zeta to IRS-2. |
| 746 | 14722023 | Insulin-like growth factor I receptors are more abundant than insulin receptors in human micro- and macrovascular endothelial cells. |
| 747 | 14722023 | Our aim was to characterize IGF-I receptor (IGF-IR) and insulin receptor (IR) in human micro- and macrovascular endothelial cells. |
| 748 | 14722023 | Insulin and the new, long-acting insulin analog glargine interacted with the IGF-IR with thousand- and hundred-fold less potency than IGF-I itself. |
| 749 | 14722023 | Phosphorylation of the IGF-IR beta-subunit was shown in HAEC for IGF-I (10(-8) M) and insulin (10(-6) M) and in HMVEC for IGF-I and glargine (10(-8) M, 10(-6) M). |
| 750 | 14722023 | IGF-I 10(-7) M stimulated incorporation of [(3)H]thymidine into DNA, and 10(-9)-10(-7) M also the incorporation of [(3)H]glucose in HMVEC, whereas glargine and insulin had no significant effects at 10(-9)-10(-7) M. |
| 751 | 14722023 | IGF-I and high concentrations of glargine and insulin activates the IGF-IR. |
| 752 | 14722023 | Glargine has a higher affinity than insulin for the IGF-IR but probably has no effect on DNA synthesis at concentrations reached in vivo. |
| 753 | 14722023 | Insulin-like growth factor I receptors are more abundant than insulin receptors in human micro- and macrovascular endothelial cells. |
| 754 | 14722023 | Our aim was to characterize IGF-I receptor (IGF-IR) and insulin receptor (IR) in human micro- and macrovascular endothelial cells. |
| 755 | 14722023 | Insulin and the new, long-acting insulin analog glargine interacted with the IGF-IR with thousand- and hundred-fold less potency than IGF-I itself. |
| 756 | 14722023 | Phosphorylation of the IGF-IR beta-subunit was shown in HAEC for IGF-I (10(-8) M) and insulin (10(-6) M) and in HMVEC for IGF-I and glargine (10(-8) M, 10(-6) M). |
| 757 | 14722023 | IGF-I 10(-7) M stimulated incorporation of [(3)H]thymidine into DNA, and 10(-9)-10(-7) M also the incorporation of [(3)H]glucose in HMVEC, whereas glargine and insulin had no significant effects at 10(-9)-10(-7) M. |
| 758 | 14722023 | IGF-I and high concentrations of glargine and insulin activates the IGF-IR. |
| 759 | 14722023 | Glargine has a higher affinity than insulin for the IGF-IR but probably has no effect on DNA synthesis at concentrations reached in vivo. |
| 760 | 14722023 | Insulin-like growth factor I receptors are more abundant than insulin receptors in human micro- and macrovascular endothelial cells. |
| 761 | 14722023 | Our aim was to characterize IGF-I receptor (IGF-IR) and insulin receptor (IR) in human micro- and macrovascular endothelial cells. |
| 762 | 14722023 | Insulin and the new, long-acting insulin analog glargine interacted with the IGF-IR with thousand- and hundred-fold less potency than IGF-I itself. |
| 763 | 14722023 | Phosphorylation of the IGF-IR beta-subunit was shown in HAEC for IGF-I (10(-8) M) and insulin (10(-6) M) and in HMVEC for IGF-I and glargine (10(-8) M, 10(-6) M). |
| 764 | 14722023 | IGF-I 10(-7) M stimulated incorporation of [(3)H]thymidine into DNA, and 10(-9)-10(-7) M also the incorporation of [(3)H]glucose in HMVEC, whereas glargine and insulin had no significant effects at 10(-9)-10(-7) M. |
| 765 | 14722023 | IGF-I and high concentrations of glargine and insulin activates the IGF-IR. |
| 766 | 14722023 | Glargine has a higher affinity than insulin for the IGF-IR but probably has no effect on DNA synthesis at concentrations reached in vivo. |
| 767 | 14722023 | Insulin-like growth factor I receptors are more abundant than insulin receptors in human micro- and macrovascular endothelial cells. |
| 768 | 14722023 | Our aim was to characterize IGF-I receptor (IGF-IR) and insulin receptor (IR) in human micro- and macrovascular endothelial cells. |
| 769 | 14722023 | Insulin and the new, long-acting insulin analog glargine interacted with the IGF-IR with thousand- and hundred-fold less potency than IGF-I itself. |
| 770 | 14722023 | Phosphorylation of the IGF-IR beta-subunit was shown in HAEC for IGF-I (10(-8) M) and insulin (10(-6) M) and in HMVEC for IGF-I and glargine (10(-8) M, 10(-6) M). |
| 771 | 14722023 | IGF-I 10(-7) M stimulated incorporation of [(3)H]thymidine into DNA, and 10(-9)-10(-7) M also the incorporation of [(3)H]glucose in HMVEC, whereas glargine and insulin had no significant effects at 10(-9)-10(-7) M. |
| 772 | 14722023 | IGF-I and high concentrations of glargine and insulin activates the IGF-IR. |
| 773 | 14722023 | Glargine has a higher affinity than insulin for the IGF-IR but probably has no effect on DNA synthesis at concentrations reached in vivo. |
| 774 | 14722023 | Insulin-like growth factor I receptors are more abundant than insulin receptors in human micro- and macrovascular endothelial cells. |
| 775 | 14722023 | Our aim was to characterize IGF-I receptor (IGF-IR) and insulin receptor (IR) in human micro- and macrovascular endothelial cells. |
| 776 | 14722023 | Insulin and the new, long-acting insulin analog glargine interacted with the IGF-IR with thousand- and hundred-fold less potency than IGF-I itself. |
| 777 | 14722023 | Phosphorylation of the IGF-IR beta-subunit was shown in HAEC for IGF-I (10(-8) M) and insulin (10(-6) M) and in HMVEC for IGF-I and glargine (10(-8) M, 10(-6) M). |
| 778 | 14722023 | IGF-I 10(-7) M stimulated incorporation of [(3)H]thymidine into DNA, and 10(-9)-10(-7) M also the incorporation of [(3)H]glucose in HMVEC, whereas glargine and insulin had no significant effects at 10(-9)-10(-7) M. |
| 779 | 14722023 | IGF-I and high concentrations of glargine and insulin activates the IGF-IR. |
| 780 | 14722023 | Glargine has a higher affinity than insulin for the IGF-IR but probably has no effect on DNA synthesis at concentrations reached in vivo. |
| 781 | 14737113 | PTEN inhibits cell proliferation and induces apoptosis by downregulating cell surface IGF-IR expression in prostate cancer cells. |
| 782 | 14737113 | PTEN appears to play a crucial role in modulating apoptosis by reducing the levels of PtdIns(3,4,5)P3, a phospholipid that activates AKT, a central regulator of apoptosis. |
| 783 | 14737113 | Interestingly, PTEN overexpression resulted in a 44-60% reduction in total insulin-like growth factor-I receptor (IGF-IR) protein levels and a 49-64% reduction in cell surface IGF-IR expression. [35S]methionine pulse experiments in PC3 cells overexpressing PTEN demonstrated that these cells synthesize significantly lower levels of the IGF-IR precursor, whereas PTEN overexpression had no effect on IGF-IR degradation. |
| 784 | 14737113 | Taken together, our results show that PTEN can regulate cell proliferation and apoptosis through inhibition of IGF-IR synthesis. |
| 785 | 14737113 | These results have important implications for understanding the roles of PTEN and the IGF-IR in prostate cancer cell tumorigenesis. |
| 786 | 14737113 | PTEN inhibits cell proliferation and induces apoptosis by downregulating cell surface IGF-IR expression in prostate cancer cells. |
| 787 | 14737113 | PTEN appears to play a crucial role in modulating apoptosis by reducing the levels of PtdIns(3,4,5)P3, a phospholipid that activates AKT, a central regulator of apoptosis. |
| 788 | 14737113 | Interestingly, PTEN overexpression resulted in a 44-60% reduction in total insulin-like growth factor-I receptor (IGF-IR) protein levels and a 49-64% reduction in cell surface IGF-IR expression. [35S]methionine pulse experiments in PC3 cells overexpressing PTEN demonstrated that these cells synthesize significantly lower levels of the IGF-IR precursor, whereas PTEN overexpression had no effect on IGF-IR degradation. |
| 789 | 14737113 | Taken together, our results show that PTEN can regulate cell proliferation and apoptosis through inhibition of IGF-IR synthesis. |
| 790 | 14737113 | These results have important implications for understanding the roles of PTEN and the IGF-IR in prostate cancer cell tumorigenesis. |
| 791 | 14737113 | PTEN inhibits cell proliferation and induces apoptosis by downregulating cell surface IGF-IR expression in prostate cancer cells. |
| 792 | 14737113 | PTEN appears to play a crucial role in modulating apoptosis by reducing the levels of PtdIns(3,4,5)P3, a phospholipid that activates AKT, a central regulator of apoptosis. |
| 793 | 14737113 | Interestingly, PTEN overexpression resulted in a 44-60% reduction in total insulin-like growth factor-I receptor (IGF-IR) protein levels and a 49-64% reduction in cell surface IGF-IR expression. [35S]methionine pulse experiments in PC3 cells overexpressing PTEN demonstrated that these cells synthesize significantly lower levels of the IGF-IR precursor, whereas PTEN overexpression had no effect on IGF-IR degradation. |
| 794 | 14737113 | Taken together, our results show that PTEN can regulate cell proliferation and apoptosis through inhibition of IGF-IR synthesis. |
| 795 | 14737113 | These results have important implications for understanding the roles of PTEN and the IGF-IR in prostate cancer cell tumorigenesis. |
| 796 | 14737113 | PTEN inhibits cell proliferation and induces apoptosis by downregulating cell surface IGF-IR expression in prostate cancer cells. |
| 797 | 14737113 | PTEN appears to play a crucial role in modulating apoptosis by reducing the levels of PtdIns(3,4,5)P3, a phospholipid that activates AKT, a central regulator of apoptosis. |
| 798 | 14737113 | Interestingly, PTEN overexpression resulted in a 44-60% reduction in total insulin-like growth factor-I receptor (IGF-IR) protein levels and a 49-64% reduction in cell surface IGF-IR expression. [35S]methionine pulse experiments in PC3 cells overexpressing PTEN demonstrated that these cells synthesize significantly lower levels of the IGF-IR precursor, whereas PTEN overexpression had no effect on IGF-IR degradation. |
| 799 | 14737113 | Taken together, our results show that PTEN can regulate cell proliferation and apoptosis through inhibition of IGF-IR synthesis. |
| 800 | 14737113 | These results have important implications for understanding the roles of PTEN and the IGF-IR in prostate cancer cell tumorigenesis. |
| 801 | 14970008 | Molecular characterization of predifferentiated cultured cells was performed by real-time PCR measurements of glucocorticoid receptor-alpha (GRalpha), insulin-like growth factor I receptor (IGF-IR), peroxisome proliferator-activated receptor-gamma (PPARgamma), enhancer-binding protein GATA-3, CCAAT/enhancer-binding protein-alpha undifferentiated protein (CUP/AP-2alpha), and endothelial cell-specific marker 2 (ECSM2). |
| 802 | 14970008 | The mRNA concentrations of GRalpha correlated with PDIFF (r = 0.29, P = 0.03), but the others did not (IGF-IR, r = 0.003, P = 1.0; PPARgamma, r = -0.1, P = 0.5; GATA-3, r = 0.02, P = 0.9; CUP/AP-2alpha, r = -0.2, P = 0.1; ECSM2, r = 0.04, P = 0.7). |
| 803 | 14970008 | Molecular characterization of predifferentiated cultured cells was performed by real-time PCR measurements of glucocorticoid receptor-alpha (GRalpha), insulin-like growth factor I receptor (IGF-IR), peroxisome proliferator-activated receptor-gamma (PPARgamma), enhancer-binding protein GATA-3, CCAAT/enhancer-binding protein-alpha undifferentiated protein (CUP/AP-2alpha), and endothelial cell-specific marker 2 (ECSM2). |
| 804 | 14970008 | The mRNA concentrations of GRalpha correlated with PDIFF (r = 0.29, P = 0.03), but the others did not (IGF-IR, r = 0.003, P = 1.0; PPARgamma, r = -0.1, P = 0.5; GATA-3, r = 0.02, P = 0.9; CUP/AP-2alpha, r = -0.2, P = 0.1; ECSM2, r = 0.04, P = 0.7). |
| 805 | 14997011 | Modulation of brain insulin-like growth factor I (IGF-I) binding sites and hypothalamic GHRH and somatostatin levels by exogenous growth hormone and IGF-I in juvenile rats. |
| 806 | 14997011 | The effect of exogenous growth hormone (GH) and insulin-like growth factor I (IGF-I) on brain IGF-I binding sites (IGF-IR), and on the levels of growth hormone-releasing hormone (GHRH) and somatostatin was studied in hypophysectomized and intact juvenile male rats. |
| 807 | 14997011 | There was a significant increase in IGF-IR binding capacity in the IGF-I-treated hypophysectomized rats compared to the saline-treated hypophysectomized animals (150.61 +/- 45.66 vs 41.32 +/- 12.42 fmol/mg, p < 0.05) but no significant difference in IGF-IR mRNA levels. |
| 808 | 14997011 | GHRH levels in the saline-treated hypophysectomized group were significantly lower than in the saline-treated intact rats (31.2 +/- 11.2 vs 140.6 +/- 48.1 pg/mg tissue, respectively, p < 0.01); no effect was induced by GH or IGF-I (37.5 +/- 26.8 and 53.8 +/- 22.5 pg/mg tissue, respectively). |
| 809 | 14997011 | However, in the intact rats, GH and IGF-I injection led to a decrease in GHRH content, which was significant in the GH-treated compared to the saline-treated animals (33.1 +/- 16.2 vs 140.6 +/- 48.1 pg/mg tissue, p < 0.01). |
| 810 | 14997011 | However, in the hypophysectomized animals, GH and IGF-I treatment induced a significant increase in somatostatin levels (1300 +/- 193.7 pg/mg tissue, p < 0.01, and 912.5 +/- 81.2 pg/mg tissue, p < 0.05, respectively). |
| 811 | 14997011 | Modulation of brain insulin-like growth factor I (IGF-I) binding sites and hypothalamic GHRH and somatostatin levels by exogenous growth hormone and IGF-I in juvenile rats. |
| 812 | 14997011 | The effect of exogenous growth hormone (GH) and insulin-like growth factor I (IGF-I) on brain IGF-I binding sites (IGF-IR), and on the levels of growth hormone-releasing hormone (GHRH) and somatostatin was studied in hypophysectomized and intact juvenile male rats. |
| 813 | 14997011 | There was a significant increase in IGF-IR binding capacity in the IGF-I-treated hypophysectomized rats compared to the saline-treated hypophysectomized animals (150.61 +/- 45.66 vs 41.32 +/- 12.42 fmol/mg, p < 0.05) but no significant difference in IGF-IR mRNA levels. |
| 814 | 14997011 | GHRH levels in the saline-treated hypophysectomized group were significantly lower than in the saline-treated intact rats (31.2 +/- 11.2 vs 140.6 +/- 48.1 pg/mg tissue, respectively, p < 0.01); no effect was induced by GH or IGF-I (37.5 +/- 26.8 and 53.8 +/- 22.5 pg/mg tissue, respectively). |
| 815 | 14997011 | However, in the intact rats, GH and IGF-I injection led to a decrease in GHRH content, which was significant in the GH-treated compared to the saline-treated animals (33.1 +/- 16.2 vs 140.6 +/- 48.1 pg/mg tissue, p < 0.01). |
| 816 | 14997011 | However, in the hypophysectomized animals, GH and IGF-I treatment induced a significant increase in somatostatin levels (1300 +/- 193.7 pg/mg tissue, p < 0.01, and 912.5 +/- 81.2 pg/mg tissue, p < 0.05, respectively). |
| 817 | 15037619 | TDAG51 mediates the effects of insulin-like growth factor I (IGF-I) on cell survival. |
| 818 | 15037619 | Insulin-like growth factor-I (IGF-I) receptors and insulin receptors belong to the same subfamily of receptor tyrosine kinases and share a similar set of intracellular signaling pathways, despite their distinct biological actions. |
| 819 | 15037619 | In the present study, we evaluated T cell death-associated gene 51 (TDAG51), which we previously identified by cDNA microarray analysis as a gene specifically induced by IGF-I. |
| 820 | 15037619 | We characterized the signaling pathways by which IGF-I induces TDAG51 gene expression and the functional role of TDAG51 in IGF-I signaling in NIH-3T3 (NWTb3) cells, which overexpress the human IGF-I receptor. |
| 821 | 15037619 | Treatment with IGF-I increased TDAG51 mRNA and protein levels in NWTb3 cells. |
| 822 | 15037619 | This effect of IGF-I was specifically mediated by the IGF-IR, because IGF-I did not induce TDAG51 expression in NIH-3T3 cells overexpressing a dominant-negative IGF-I receptor. |
| 823 | 15037619 | Through the use of specific inhibitors of various protein kinases, we found that IGF-I induced TDAG51 expression via the p38 MAPK pathway. |
| 824 | 15037619 | The ERK, JNK, and phosphatidylinositol 3-kinase pathways were not involved in IGF-I-induced regulation of TDAG51. |
| 825 | 15037619 | To assess the role of TDAG51 in IGF-I signaling, we used small interfering RNA (siRNA) expression vectors directed at two different target sites to reduce the level of TDAG51 protein. |
| 826 | 15037619 | Furthermore, TDAG51 siRNA expression abolished the ability of IGF-I to rescue cells from serum starvation-induced apoptosis. |
| 827 | 15037619 | These findings suggest that TDAG51 plays an important role in the anti-apoptotic effects of IGF-I. |
| 828 | 15181035 | Seventy-two PCOS patients and 42 healthy controls were genotyped for 15 variants in the genes encoding for paraoxonase (three variants), plasma cell differentiation antigen glycoprotein, human sorbin and SH3 domain containing 1, plasminogen activator inhibitor-1, peroxisome proliferator-activated receptor-gamma2, protein tyrosine phosphatase 1B (two variants), adiponectin (two variants), IGF1, IGF2, IGF1 receptor, and IGF2 receptor. |
| 829 | 15181035 | Compared with controls, PCOS patients were more frequently homozygous for the -108T variant in paraoxonase (36.6% vs. 9.5%; P = 0.002) and homozygous for G alleles of the ApaI variant in IGF2 (62.9% vs. 38.1%; P = 0.018). |
| 830 | 15181035 | Paraoxonase is a serum antioxidant enzyme and, because -108T alleles result in decreased paraoxonase expression, this increase in oxidative stress might result in insulin resistance. |
| 831 | 15181035 | In conclusion, the paraoxonase -108 C-->T variant and the ApaI polymorphism in the IGF2 gene are associated with PCOS and might contribute to increased oxidative stress, insulin resistance, and hyperandrogenism in this prevalent disorder. |
| 832 | 15378031 | The APS, SH2-B and LNK proteins are adapters that activate and modulate receptor tyrosine kinase and JAK/STAT signaling. |
| 833 | 15378031 | A newly developed bridging yeast tri-hybrid assay showed that APS dimerizes JAK2, insulin receptor and IGF1 receptor kinases using its SH2 and dimerization domains. |
| 834 | 15561943 | The dogma that IGF-I stimulates pancreatic islet growth has been challenged by combinational targeting of IGF or IGF-IR (IGF receptor) genes as well as beta-cell-specific IGF-IR gene deficiency, which caused no defect in islet cell growth. |
| 835 | 15561943 | To assess the physiological role of locally produced IGF-I, we have developed pancreatic-specific IGF-I gene deficiency (PID) by crossing Pdx1-Cre and IGF-I/loxP mice. |
| 836 | 15585589 | IGF-I downregulates resistin gene expression and protein secretion. |
| 837 | 15585589 | Resistin (Rstn) is known as an adipocyte-specific secretory factor that can cause insulin resistance and decrease adipocyte differentiation. |
| 838 | 15585589 | Conversely, based on various studies, insulin-like growth factors (IGFs) can improve insulin resistance and stimulate adipocyte adipogenesis. |
| 839 | 15585589 | This study was designed to examine the influence and the signaling of IGF-I on Rstn gene expression and protein secretion by 3T3-L1 adipocytes. |
| 840 | 15585589 | We found that IGF-I suppressed Rstn mRNA expression and protein release in dose- and time-dependent manners. |
| 841 | 15585589 | Treatment with cycloheximide, but not with actinomycin D, prevented IGF-I-suppressed Rstn mRNA expression, suggesting that IGF-I destabilizes Rstn mRNA and that IGF-I's effect requires new protein, but not mRNA, synthesis. |
| 842 | 15585589 | Pretreatment with IGF-I receptor (IGF-IR) antibody blocked IGF-I-altered IGF-IR activity and Rstn mRNA levels. |
| 843 | 15585589 | Neither PD-98059, SB-203580, nor LY-294002 changed the IGF-I-decreased levels of Rstn mRNA, but they inhibited IGF-I-stimulated activities of MEK1, p38 MAPK, and phosphoinositide 3-kinase, respectively. |
| 844 | 15585589 | These data demonstrate that IGF-I downregulates Rstn gene expression via IGF-IR-dependent and MEK1-, p38 MAPK-, and phosphoinositide 3-kinase-independent pathways and likely modifies the distribution of Rstn protein between the intracellular and extracellular compartments via a p38 MAPK-dependent pathway. |
| 845 | 15585589 | Decreases in Rstn production and secretion induced by IGF-I may be related to the mechanism by which IGF-I modulates body weight and diabetes in animals. |
| 846 | 15590636 | To determine the molecular mechanism by which this polymorphism may be linked to insulin resistance, we produced recombinant peptides comprising amino acid residues 925-1008 from IRS-1 that contain either a glycine or arginine at codon 972 and the two nearby tyrosine phosphorylation consensus sites (EY(941)MLM and DY(989)MTM), which are known binding sites for the p85alpha regulatory subunit of phosphatidylinositol 3-kinase. |
| 847 | 15590636 | The use of additional overlapping fragments localized this interaction to domains between residues 950-986 of IRS-1 and residues 966-1271 of the insulin receptor, containing the tyrosine kinase domain of the receptor. |
| 848 | 15590636 | In addition, the IRS-1-(925-1008) G972R peptide acted as a competitive inhibitor of insulin receptor and insulin-like growth factor-1 receptor autophosphorylation. |
| 849 | 15590636 | Taken together, these data indicate that the G972R naturally occurring polymorphism of IRS-1 not only reduces phosphorylation of the substrate but allows IRS-1 to act as an inhibitor of the insulin receptor kinase, producing global insulin resistance. |
| 850 | 15607526 | IGF-I receptors (IGF-IR) and insulin receptors (IR) in endothelial cells might respond to altered levels of IGF-I and insulin, resulting in altered endothelial function in diabetes. |
| 851 | 15752742 | Meg1/Grb10 overexpression causes postnatal growth retardation and insulin resistance via negative modulation of the IGF1R and IR cascades. |
| 852 | 15752742 | The Meg1/Grb10 protein has been implicated as an adapter protein in the signaling pathways from insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R) in vitro. |
| 853 | 15752742 | All of the Meg1/Grb10 transgenic mice showed growth retardation after weaning (3-4 weeks), which indicates that ectopic overexpression of Meg1/Grb10 inhibits postnatal growth that is mediated by IGF1 via IGF1R. |
| 854 | 15752742 | In addition, the mice became hyperinsulinemic owing to high levels of insulin resistance, which demonstrates that Meg1/Grb10 also modulates the insulin receptor cascade negatively in vivo. |
| 855 | 15752742 | These results suggest that Meg1/Grb10 inhibits the function of both insulin and IGF1 receptors in these cells, since a similar phenotype has been reported for Ir and Igf1r double knockout mice. |
| 856 | 15752742 | Taken together, these results indicate that Meg1/Grb10 interacts with both insulin and IGF1 receptors in vivo, and negatively regulates the IGF growth pathways via these receptors. |
| 857 | 15752742 | Meg1/Grb10 overexpression causes postnatal growth retardation and insulin resistance via negative modulation of the IGF1R and IR cascades. |
| 858 | 15752742 | The Meg1/Grb10 protein has been implicated as an adapter protein in the signaling pathways from insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R) in vitro. |
| 859 | 15752742 | All of the Meg1/Grb10 transgenic mice showed growth retardation after weaning (3-4 weeks), which indicates that ectopic overexpression of Meg1/Grb10 inhibits postnatal growth that is mediated by IGF1 via IGF1R. |
| 860 | 15752742 | In addition, the mice became hyperinsulinemic owing to high levels of insulin resistance, which demonstrates that Meg1/Grb10 also modulates the insulin receptor cascade negatively in vivo. |
| 861 | 15752742 | These results suggest that Meg1/Grb10 inhibits the function of both insulin and IGF1 receptors in these cells, since a similar phenotype has been reported for Ir and Igf1r double knockout mice. |
| 862 | 15752742 | Taken together, these results indicate that Meg1/Grb10 interacts with both insulin and IGF1 receptors in vivo, and negatively regulates the IGF growth pathways via these receptors. |
| 863 | 15752742 | Meg1/Grb10 overexpression causes postnatal growth retardation and insulin resistance via negative modulation of the IGF1R and IR cascades. |
| 864 | 15752742 | The Meg1/Grb10 protein has been implicated as an adapter protein in the signaling pathways from insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R) in vitro. |
| 865 | 15752742 | All of the Meg1/Grb10 transgenic mice showed growth retardation after weaning (3-4 weeks), which indicates that ectopic overexpression of Meg1/Grb10 inhibits postnatal growth that is mediated by IGF1 via IGF1R. |
| 866 | 15752742 | In addition, the mice became hyperinsulinemic owing to high levels of insulin resistance, which demonstrates that Meg1/Grb10 also modulates the insulin receptor cascade negatively in vivo. |
| 867 | 15752742 | These results suggest that Meg1/Grb10 inhibits the function of both insulin and IGF1 receptors in these cells, since a similar phenotype has been reported for Ir and Igf1r double knockout mice. |
| 868 | 15752742 | Taken together, these results indicate that Meg1/Grb10 interacts with both insulin and IGF1 receptors in vivo, and negatively regulates the IGF growth pathways via these receptors. |
| 869 | 15752742 | Meg1/Grb10 overexpression causes postnatal growth retardation and insulin resistance via negative modulation of the IGF1R and IR cascades. |
| 870 | 15752742 | The Meg1/Grb10 protein has been implicated as an adapter protein in the signaling pathways from insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R) in vitro. |
| 871 | 15752742 | All of the Meg1/Grb10 transgenic mice showed growth retardation after weaning (3-4 weeks), which indicates that ectopic overexpression of Meg1/Grb10 inhibits postnatal growth that is mediated by IGF1 via IGF1R. |
| 872 | 15752742 | In addition, the mice became hyperinsulinemic owing to high levels of insulin resistance, which demonstrates that Meg1/Grb10 also modulates the insulin receptor cascade negatively in vivo. |
| 873 | 15752742 | These results suggest that Meg1/Grb10 inhibits the function of both insulin and IGF1 receptors in these cells, since a similar phenotype has been reported for Ir and Igf1r double knockout mice. |
| 874 | 15752742 | Taken together, these results indicate that Meg1/Grb10 interacts with both insulin and IGF1 receptors in vivo, and negatively regulates the IGF growth pathways via these receptors. |
| 875 | 15812560 | Insulin-like growth factor-I receptor activity is essential for Kaposi's sarcoma growth and survival. |
| 876 | 15812560 | The role of insulin-like growth factors (IGFs) in the pathophysiology of different tumours led us to evaluate the role of IGF system in KS. |
| 877 | 15812560 | The IGF-I receptors (IGF-IR) were identified by immunohistochemistry in biopsies taken from patients with different AIDS/HIV-related KS stages and on KSIMM cells (an established KS-derived cell line). |
| 878 | 15812560 | Insulin-like growth factor-I is a growth factor for KSIMM cells with a maximum increase of 3H-thymidine incorporation of 130 +/- 27.6% (P < 0.05) similar to that induced by VEGF and with which it is additive (281 +/- 13%) (P < 0.05). |
| 879 | 15812560 | Moreover, specific blockade of the receptor (either by alpha IR3 antibody or by picropodophyllin, a recently described selective IGF-IR tyrosine phosphorylation inhibitor) induced KSIMM apoptosis, suggesting that IGF-IR agonists (IGF-I and -II) mediate antiapoptotic signals for these cells. |
| 880 | 15812560 | We were able to identify an autocrine loop essential for KSIMM cell survival in which IGF-II is the IGF-IR agonist secreted by the cells. |
| 881 | 15812560 | Insulin-like growth factor-I receptor activity is essential for Kaposi's sarcoma growth and survival. |
| 882 | 15812560 | The role of insulin-like growth factors (IGFs) in the pathophysiology of different tumours led us to evaluate the role of IGF system in KS. |
| 883 | 15812560 | The IGF-I receptors (IGF-IR) were identified by immunohistochemistry in biopsies taken from patients with different AIDS/HIV-related KS stages and on KSIMM cells (an established KS-derived cell line). |
| 884 | 15812560 | Insulin-like growth factor-I is a growth factor for KSIMM cells with a maximum increase of 3H-thymidine incorporation of 130 +/- 27.6% (P < 0.05) similar to that induced by VEGF and with which it is additive (281 +/- 13%) (P < 0.05). |
| 885 | 15812560 | Moreover, specific blockade of the receptor (either by alpha IR3 antibody or by picropodophyllin, a recently described selective IGF-IR tyrosine phosphorylation inhibitor) induced KSIMM apoptosis, suggesting that IGF-IR agonists (IGF-I and -II) mediate antiapoptotic signals for these cells. |
| 886 | 15812560 | We were able to identify an autocrine loop essential for KSIMM cell survival in which IGF-II is the IGF-IR agonist secreted by the cells. |
| 887 | 15812560 | Insulin-like growth factor-I receptor activity is essential for Kaposi's sarcoma growth and survival. |
| 888 | 15812560 | The role of insulin-like growth factors (IGFs) in the pathophysiology of different tumours led us to evaluate the role of IGF system in KS. |
| 889 | 15812560 | The IGF-I receptors (IGF-IR) were identified by immunohistochemistry in biopsies taken from patients with different AIDS/HIV-related KS stages and on KSIMM cells (an established KS-derived cell line). |
| 890 | 15812560 | Insulin-like growth factor-I is a growth factor for KSIMM cells with a maximum increase of 3H-thymidine incorporation of 130 +/- 27.6% (P < 0.05) similar to that induced by VEGF and with which it is additive (281 +/- 13%) (P < 0.05). |
| 891 | 15812560 | Moreover, specific blockade of the receptor (either by alpha IR3 antibody or by picropodophyllin, a recently described selective IGF-IR tyrosine phosphorylation inhibitor) induced KSIMM apoptosis, suggesting that IGF-IR agonists (IGF-I and -II) mediate antiapoptotic signals for these cells. |
| 892 | 15812560 | We were able to identify an autocrine loop essential for KSIMM cell survival in which IGF-II is the IGF-IR agonist secreted by the cells. |
| 893 | 16142439 | Nordihydroguaiaretic acid (NDGA) inhibits the IGF-1 and c-erbB2/HER2/neu receptors and suppresses growth in breast cancer cells. |
| 894 | 16142439 | We can now attribute certain of these anti-cancer properties in breast cancer cells to the ability of NDGA to directly inhibit the function of two receptor tyrosine kinases (RTKs), the insulin-like growth factor receptor (IGF-1R) and the c-erbB2/HER2/neu (HER2/neu) receptor. |
| 895 | 16142439 | In MCF-7 human breast cancer cells, low micromolar concentrations of NDGA inhibited activation of the IGF-1R, and downstream phosphorylation of both the Akt/PKB serine kinase and the pro-apoptotic protein BAD. |
| 896 | 16142439 | NDGA treatment (intraperitoneal injection 3 times per week) also decreased the activity of the IGF-1R and the HER2/neu receptor in MCNeuA cells implanted into mice. |
| 897 | 16142439 | Nordihydroguaiaretic acid (NDGA) inhibits the IGF-1 and c-erbB2/HER2/neu receptors and suppresses growth in breast cancer cells. |
| 898 | 16142439 | We can now attribute certain of these anti-cancer properties in breast cancer cells to the ability of NDGA to directly inhibit the function of two receptor tyrosine kinases (RTKs), the insulin-like growth factor receptor (IGF-1R) and the c-erbB2/HER2/neu (HER2/neu) receptor. |
| 899 | 16142439 | In MCF-7 human breast cancer cells, low micromolar concentrations of NDGA inhibited activation of the IGF-1R, and downstream phosphorylation of both the Akt/PKB serine kinase and the pro-apoptotic protein BAD. |
| 900 | 16142439 | NDGA treatment (intraperitoneal injection 3 times per week) also decreased the activity of the IGF-1R and the HER2/neu receptor in MCNeuA cells implanted into mice. |
| 901 | 16142439 | Nordihydroguaiaretic acid (NDGA) inhibits the IGF-1 and c-erbB2/HER2/neu receptors and suppresses growth in breast cancer cells. |
| 902 | 16142439 | We can now attribute certain of these anti-cancer properties in breast cancer cells to the ability of NDGA to directly inhibit the function of two receptor tyrosine kinases (RTKs), the insulin-like growth factor receptor (IGF-1R) and the c-erbB2/HER2/neu (HER2/neu) receptor. |
| 903 | 16142439 | In MCF-7 human breast cancer cells, low micromolar concentrations of NDGA inhibited activation of the IGF-1R, and downstream phosphorylation of both the Akt/PKB serine kinase and the pro-apoptotic protein BAD. |
| 904 | 16142439 | NDGA treatment (intraperitoneal injection 3 times per week) also decreased the activity of the IGF-1R and the HER2/neu receptor in MCNeuA cells implanted into mice. |
| 905 | 16287721 | Learning-specific increases in levels of downstream molecules such as IRS-1 and Akt were detected in the synaptic membrane accompanied by decreases in Akt phosphorylation. |
| 906 | 16287721 | Translocation of Shc protein to the synaptic membrane and activation of Erk1/2 were also observed after long-term memory formation. |
| 907 | 16287721 | This may be due to higher glucose levels in the DM brain, and to compensatory mechanisms from other signaling pathways such as the insulin-like growth factor-1 receptor (IGF-1R) system. |
| 908 | 16350721 | Several genes from these pathways have been tested include genes involved in steroid hormone biosynthesis and metabolism (StAR, CYP11, CYP17, CYP19 HSD17B1-3, HSD3B1-2), gonadotropin and gonadal hormones action (ACTR1, ACTR2A-B, FS, INHA, INHBA-B, INHC, SHBG, LHCGR, FSHR, MADH4, AR), obesity and energy regulation (MC4R, OB, OBR, POMC, UCP2-3), insulin secretion and action (IGF1, IGF1R, IGFBPI1-3, INS VNTR, IR, INSL, IRS1-2, PPARG) and many others. |
| 909 | 16350721 | Polymorphic alleles of both IRS-1 and IRS-2 (insulin receptor substrate 1 - 2), alone or in combination, may have a functional impact on the insulin-resistant component of PCOS. |
| 910 | 16350721 | There is no evidence to suggest that follistatin gene polymorphisms play a role in the pathogenesis of insulin resistance in PCOS women. |
| 911 | 16350721 | The results of this study demonstrate that there are significant alterations in the expression of ERalpha and ERbeta in PCOS that may be related to abnormal follicular development. |
| 912 | 16569742 | Clinical and functional characteristics of the human Arg59Ter insulin-like growth factor i receptor (IGF1R) mutation: implications for a gene dosage effect of the human IGF1R. |
| 913 | 16648580 | Diarylureas are small-molecule inhibitors of insulin-like growth factor I receptor signaling and breast cancer cell growth. |
| 914 | 16648580 | In breast and certain other cancers, receptor tyrosine kinases, including the insulin-like growth factor I receptor (IGF-IR), play an important role in promoting the oncogenic process. |
| 915 | 16648580 | Treatment of MCF-7 cells with PQ401 was associated with a decrease in IGF-I-mediated signaling through the Akt antiapoptotic pathway. |
| 916 | 16750336 | Insulin-like growth factor-1 receptor expression in the placentae of diabetic and normal pregnancies. |
| 917 | 16981720 | Involvement of insulin-like growth factor type 1 receptor and protein kinase Cdelta in bis(maltolato)oxovanadium(IV)-induced phosphorylation of protein kinase B in HepG2 cells. |
| 918 | 16981720 | In contrast, AG1295 and AG1478, specific inhibitors of PDGFR and EGFR, respectively, were unable to block the BMOV response. |
| 919 | 16981720 | Moreover, efficient reduction of the level of IGF-1R protein expression by antisense oligonucleotides (ASO) attenuated BMOV-induced PKB phosphorylation. |
| 920 | 16981720 | BMOV-induced PKB phosphorylation was associated with an increased level of tyrosine phosphorylation of the IRbeta subunit, IGF-1Rbeta subunit, IRS-1, and p85alpha subunit of PI3-kinase. |
| 921 | 16981720 | However, this response was independent of IR-PTK activity because in cells overexpressing a PTK-inactive form of IR, insulin response was attenuated while the effect of BMOV remained intact. |
| 922 | 16981720 | Taken together, these data suggest that IGF-1R and PKCdelta are required to stimulate PKB phosphorylation in response to BMOV in HepG2 cells and provide new insights into the molecular mechanism by which this compound exerts its insulinomimetic effects. |
| 923 | 16981720 | Involvement of insulin-like growth factor type 1 receptor and protein kinase Cdelta in bis(maltolato)oxovanadium(IV)-induced phosphorylation of protein kinase B in HepG2 cells. |
| 924 | 16981720 | In contrast, AG1295 and AG1478, specific inhibitors of PDGFR and EGFR, respectively, were unable to block the BMOV response. |
| 925 | 16981720 | Moreover, efficient reduction of the level of IGF-1R protein expression by antisense oligonucleotides (ASO) attenuated BMOV-induced PKB phosphorylation. |
| 926 | 16981720 | BMOV-induced PKB phosphorylation was associated with an increased level of tyrosine phosphorylation of the IRbeta subunit, IGF-1Rbeta subunit, IRS-1, and p85alpha subunit of PI3-kinase. |
| 927 | 16981720 | However, this response was independent of IR-PTK activity because in cells overexpressing a PTK-inactive form of IR, insulin response was attenuated while the effect of BMOV remained intact. |
| 928 | 16981720 | Taken together, these data suggest that IGF-1R and PKCdelta are required to stimulate PKB phosphorylation in response to BMOV in HepG2 cells and provide new insights into the molecular mechanism by which this compound exerts its insulinomimetic effects. |
| 929 | 17130507 | High-affinity nerve growth factor (NGF) receptor (NGFR-TrkA) expression in DRGs was significantly reduced at 4 months (P < 0.01). |
| 930 | 17130507 | Insulin receptor and IGF-I receptor (IGF-IR) expressions in DRGs and NGF content in sciatic nerve were significantly decreased in 7-month diabetic rats (P < 0.01, 0.05, and 0.005, respectively). |
| 931 | 17130507 | Osmopump delivery prevented the decline of NGFR-TrkA, insulin receptor (P < 0.05), and IGF-IR (P < 0.005) expressions in DRGs and improved NGF content (P < 0.05) in sciatic nerve. |
| 932 | 17130507 | High-affinity nerve growth factor (NGF) receptor (NGFR-TrkA) expression in DRGs was significantly reduced at 4 months (P < 0.01). |
| 933 | 17130507 | Insulin receptor and IGF-I receptor (IGF-IR) expressions in DRGs and NGF content in sciatic nerve were significantly decreased in 7-month diabetic rats (P < 0.01, 0.05, and 0.005, respectively). |
| 934 | 17130507 | Osmopump delivery prevented the decline of NGFR-TrkA, insulin receptor (P < 0.05), and IGF-IR (P < 0.005) expressions in DRGs and improved NGF content (P < 0.05) in sciatic nerve. |
| 935 | 17189427 | Essential role of insulin and insulin-like growth factor 1 receptor signaling in cardiac development and function. |
| 936 | 17189427 | Here we show that mice with combined deficiency of the insulin receptor and insulin-like growth factor 1 (IGF-1) receptor in cardiac and skeletal muscle develop early-onset dilated cardiomyopathy and die from heart failure within the first month of life despite having a normal glucose homeostasis. |
| 937 | 17189427 | Mice lacking the insulin receptor show impaired cardiac performance at 6 months, and mice lacking the insulin receptor plus one Igf1r allele have slightly increased mortality. |
| 938 | 17189427 | Morphological characterization and oligonucleotide array analysis of gene expression demonstrate that prior to development of these physiological defects, mice with combined deficiency of both insulin and IGF-1 receptors have a coordinated down-regulation of genes encoding components of the electron transport chain and mitochondrial fatty acid beta-oxidation pathways and altered expression of contractile proteins. |
| 939 | 17189427 | Thus, while neither the insulin receptor nor IGF-1 receptor in muscle is critical for glucose homeostasis during the first month of life, signaling from these receptors, particularly the insulin receptor, is required for normal cardiac metabolism and function. |
| 940 | 17189427 | Essential role of insulin and insulin-like growth factor 1 receptor signaling in cardiac development and function. |
| 941 | 17189427 | Here we show that mice with combined deficiency of the insulin receptor and insulin-like growth factor 1 (IGF-1) receptor in cardiac and skeletal muscle develop early-onset dilated cardiomyopathy and die from heart failure within the first month of life despite having a normal glucose homeostasis. |
| 942 | 17189427 | Mice lacking the insulin receptor show impaired cardiac performance at 6 months, and mice lacking the insulin receptor plus one Igf1r allele have slightly increased mortality. |
| 943 | 17189427 | Morphological characterization and oligonucleotide array analysis of gene expression demonstrate that prior to development of these physiological defects, mice with combined deficiency of both insulin and IGF-1 receptors have a coordinated down-regulation of genes encoding components of the electron transport chain and mitochondrial fatty acid beta-oxidation pathways and altered expression of contractile proteins. |
| 944 | 17189427 | Thus, while neither the insulin receptor nor IGF-1 receptor in muscle is critical for glucose homeostasis during the first month of life, signaling from these receptors, particularly the insulin receptor, is required for normal cardiac metabolism and function. |
| 945 | 17315038 | Mechanisms of disease: metabolic effects of growth hormone and insulin-like growth factor 1. |
| 946 | 17315038 | Insulin-like growth factor (IGF) 1 is a member of a family that is involved in growth, development, cell differentiation, and metabolism. |
| 947 | 17315038 | IGF1, IGF2 and insulin act primarily through tyrosine-kinase-linked receptors--the IGF1 receptor (IGF1R) and insulin receptor (IR). |
| 948 | 17315038 | The IGF1R binds IGF1 and IGF2 with high affinity and the IR binds insulin with high affinity; however, since both receptors share a high degree of structural and functional homology, the IGF1R can bind insulin and the IR can bind the IGFs with reduced affinity. |
| 949 | 17315038 | The IGF2 receptor is a scavenger receptor, and is, therefore, not involved in mediation of growth or metabolic effects of the IGF family and will not be discussed in the current article. |
| 950 | 17315038 | For example, excess growth hormone causes insulin resistance and hyperglycemia, whereas IGF1 has insulin-like effects that reduce blood glucose levels and has been used experimentally to treat both type 1 and type 2 diabetes. |
| 951 | 17315038 | Mechanisms of disease: metabolic effects of growth hormone and insulin-like growth factor 1. |
| 952 | 17315038 | Insulin-like growth factor (IGF) 1 is a member of a family that is involved in growth, development, cell differentiation, and metabolism. |
| 953 | 17315038 | IGF1, IGF2 and insulin act primarily through tyrosine-kinase-linked receptors--the IGF1 receptor (IGF1R) and insulin receptor (IR). |
| 954 | 17315038 | The IGF1R binds IGF1 and IGF2 with high affinity and the IR binds insulin with high affinity; however, since both receptors share a high degree of structural and functional homology, the IGF1R can bind insulin and the IR can bind the IGFs with reduced affinity. |
| 955 | 17315038 | The IGF2 receptor is a scavenger receptor, and is, therefore, not involved in mediation of growth or metabolic effects of the IGF family and will not be discussed in the current article. |
| 956 | 17315038 | For example, excess growth hormone causes insulin resistance and hyperglycemia, whereas IGF1 has insulin-like effects that reduce blood glucose levels and has been used experimentally to treat both type 1 and type 2 diabetes. |
| 957 | 17476475 | Defective IGF2 and IGF1R protein production in embryonic pancreas precedes beta cell mass anomaly in the Goto-Kakizaki rat model of type 2 diabetes. |
| 958 | 17487250 | Insulin-like growth factor type-1 receptor transactivation in vasoactive peptide and oxidant-induced signaling pathways in vascular smooth muscle cells. |
| 959 | 17487250 | However, a role for the insulin-like growth factor type-1 receptor (IGF-1R) transactivation in mediating the effects of angiotensin II (Ang II) and H2O2 in vascular smooth muscle cells from different artery types have also been recently recognized. |
| 960 | 17487250 | By using a series of pharmacological inhibitors of various growth factor receptor tyrosine kinases and a direct analysis of the phosphorylation status of the beta-subunit of IGF-1R, a requirement of this growth factor receptor in Ang II and H2O2 response has been demonstrated. |
| 961 | 17487250 | This review discusses some of the studies that highlight the importance of IGF-1R transactivation in mediating Ang II- and H2O2-induced mitogen-activated protein kinase and protein kinase B signaling pathways. |
| 962 | 17487250 | Insulin-like growth factor type-1 receptor transactivation in vasoactive peptide and oxidant-induced signaling pathways in vascular smooth muscle cells. |
| 963 | 17487250 | However, a role for the insulin-like growth factor type-1 receptor (IGF-1R) transactivation in mediating the effects of angiotensin II (Ang II) and H2O2 in vascular smooth muscle cells from different artery types have also been recently recognized. |
| 964 | 17487250 | By using a series of pharmacological inhibitors of various growth factor receptor tyrosine kinases and a direct analysis of the phosphorylation status of the beta-subunit of IGF-1R, a requirement of this growth factor receptor in Ang II and H2O2 response has been demonstrated. |
| 965 | 17487250 | This review discusses some of the studies that highlight the importance of IGF-1R transactivation in mediating Ang II- and H2O2-induced mitogen-activated protein kinase and protein kinase B signaling pathways. |
| 966 | 17487250 | Insulin-like growth factor type-1 receptor transactivation in vasoactive peptide and oxidant-induced signaling pathways in vascular smooth muscle cells. |
| 967 | 17487250 | However, a role for the insulin-like growth factor type-1 receptor (IGF-1R) transactivation in mediating the effects of angiotensin II (Ang II) and H2O2 in vascular smooth muscle cells from different artery types have also been recently recognized. |
| 968 | 17487250 | By using a series of pharmacological inhibitors of various growth factor receptor tyrosine kinases and a direct analysis of the phosphorylation status of the beta-subunit of IGF-1R, a requirement of this growth factor receptor in Ang II and H2O2 response has been demonstrated. |
| 969 | 17487250 | This review discusses some of the studies that highlight the importance of IGF-1R transactivation in mediating Ang II- and H2O2-induced mitogen-activated protein kinase and protein kinase B signaling pathways. |
| 970 | 17553792 | Disruption of the insulin-like growth factor type 1 receptor in osteoblasts enhances insulin signaling and action. |
| 971 | 17553792 | However, because insulin can cross-activate the insulin-like growth factor type 1 receptor (IGF-1R), which also functions in bone, it has been difficult to establish the direct (IGF-1-independent) actions of insulin in osteoblasts. |
| 972 | 17553792 | To overcome this problem, we examined insulin signaling and action in primary osteoblasts engineered for conditional disruption of the IGF-1 receptor (DeltaIGF-1R). |
| 973 | 17553792 | Disruption of IGF-1R mRNA (>90%) eliminated IGF-1R without affecting insulin receptor (IR) mRNA and protein expression and eliminated IGF-1R/IR hybrids. |
| 974 | 17553792 | In DeltaIGF-1R osteoblasts, insulin signaling was markedly increased as evidenced by increased phosphorylation of insulin receptor substrate 1/2 and enhanced ERK/Akt activation. |
| 975 | 17553792 | Microarray analysis of RNA samples from insulin-treated, DeltaIGF-1R osteoblasts revealed striking changes in several genes known to be downstream of ERK including Glut-1 and c-fos. |
| 976 | 17553792 | Treatment of osteoblasts with insulin induced Glut-1 mRNA, increased 2-[1,2-(3)H]-deoxy-d-glucose uptake, and enhanced proliferation. |
| 977 | 17553792 | Moreover, insulin treatment rescued the defective differentiation and mineralization of DeltaIGF-1R osteoblasts, suggesting that IR signaling can compensate, at least in part, for loss of IGF-1R signaling. |
| 978 | 17553792 | We conclude that insulin exerts direct anabolic actions in osteoblasts by activation of its cognate receptor and that the strength of insulin-generated signals is tempered through interactions with the IGF-1R. |
| 979 | 17553792 | Disruption of the insulin-like growth factor type 1 receptor in osteoblasts enhances insulin signaling and action. |
| 980 | 17553792 | However, because insulin can cross-activate the insulin-like growth factor type 1 receptor (IGF-1R), which also functions in bone, it has been difficult to establish the direct (IGF-1-independent) actions of insulin in osteoblasts. |
| 981 | 17553792 | To overcome this problem, we examined insulin signaling and action in primary osteoblasts engineered for conditional disruption of the IGF-1 receptor (DeltaIGF-1R). |
| 982 | 17553792 | Disruption of IGF-1R mRNA (>90%) eliminated IGF-1R without affecting insulin receptor (IR) mRNA and protein expression and eliminated IGF-1R/IR hybrids. |
| 983 | 17553792 | In DeltaIGF-1R osteoblasts, insulin signaling was markedly increased as evidenced by increased phosphorylation of insulin receptor substrate 1/2 and enhanced ERK/Akt activation. |
| 984 | 17553792 | Microarray analysis of RNA samples from insulin-treated, DeltaIGF-1R osteoblasts revealed striking changes in several genes known to be downstream of ERK including Glut-1 and c-fos. |
| 985 | 17553792 | Treatment of osteoblasts with insulin induced Glut-1 mRNA, increased 2-[1,2-(3)H]-deoxy-d-glucose uptake, and enhanced proliferation. |
| 986 | 17553792 | Moreover, insulin treatment rescued the defective differentiation and mineralization of DeltaIGF-1R osteoblasts, suggesting that IR signaling can compensate, at least in part, for loss of IGF-1R signaling. |
| 987 | 17553792 | We conclude that insulin exerts direct anabolic actions in osteoblasts by activation of its cognate receptor and that the strength of insulin-generated signals is tempered through interactions with the IGF-1R. |
| 988 | 17553792 | Disruption of the insulin-like growth factor type 1 receptor in osteoblasts enhances insulin signaling and action. |
| 989 | 17553792 | However, because insulin can cross-activate the insulin-like growth factor type 1 receptor (IGF-1R), which also functions in bone, it has been difficult to establish the direct (IGF-1-independent) actions of insulin in osteoblasts. |
| 990 | 17553792 | To overcome this problem, we examined insulin signaling and action in primary osteoblasts engineered for conditional disruption of the IGF-1 receptor (DeltaIGF-1R). |
| 991 | 17553792 | Disruption of IGF-1R mRNA (>90%) eliminated IGF-1R without affecting insulin receptor (IR) mRNA and protein expression and eliminated IGF-1R/IR hybrids. |
| 992 | 17553792 | In DeltaIGF-1R osteoblasts, insulin signaling was markedly increased as evidenced by increased phosphorylation of insulin receptor substrate 1/2 and enhanced ERK/Akt activation. |
| 993 | 17553792 | Microarray analysis of RNA samples from insulin-treated, DeltaIGF-1R osteoblasts revealed striking changes in several genes known to be downstream of ERK including Glut-1 and c-fos. |
| 994 | 17553792 | Treatment of osteoblasts with insulin induced Glut-1 mRNA, increased 2-[1,2-(3)H]-deoxy-d-glucose uptake, and enhanced proliferation. |
| 995 | 17553792 | Moreover, insulin treatment rescued the defective differentiation and mineralization of DeltaIGF-1R osteoblasts, suggesting that IR signaling can compensate, at least in part, for loss of IGF-1R signaling. |
| 996 | 17553792 | We conclude that insulin exerts direct anabolic actions in osteoblasts by activation of its cognate receptor and that the strength of insulin-generated signals is tempered through interactions with the IGF-1R. |
| 997 | 17553792 | Disruption of the insulin-like growth factor type 1 receptor in osteoblasts enhances insulin signaling and action. |
| 998 | 17553792 | However, because insulin can cross-activate the insulin-like growth factor type 1 receptor (IGF-1R), which also functions in bone, it has been difficult to establish the direct (IGF-1-independent) actions of insulin in osteoblasts. |
| 999 | 17553792 | To overcome this problem, we examined insulin signaling and action in primary osteoblasts engineered for conditional disruption of the IGF-1 receptor (DeltaIGF-1R). |
| 1000 | 17553792 | Disruption of IGF-1R mRNA (>90%) eliminated IGF-1R without affecting insulin receptor (IR) mRNA and protein expression and eliminated IGF-1R/IR hybrids. |
| 1001 | 17553792 | In DeltaIGF-1R osteoblasts, insulin signaling was markedly increased as evidenced by increased phosphorylation of insulin receptor substrate 1/2 and enhanced ERK/Akt activation. |
| 1002 | 17553792 | Microarray analysis of RNA samples from insulin-treated, DeltaIGF-1R osteoblasts revealed striking changes in several genes known to be downstream of ERK including Glut-1 and c-fos. |
| 1003 | 17553792 | Treatment of osteoblasts with insulin induced Glut-1 mRNA, increased 2-[1,2-(3)H]-deoxy-d-glucose uptake, and enhanced proliferation. |
| 1004 | 17553792 | Moreover, insulin treatment rescued the defective differentiation and mineralization of DeltaIGF-1R osteoblasts, suggesting that IR signaling can compensate, at least in part, for loss of IGF-1R signaling. |
| 1005 | 17553792 | We conclude that insulin exerts direct anabolic actions in osteoblasts by activation of its cognate receptor and that the strength of insulin-generated signals is tempered through interactions with the IGF-1R. |
| 1006 | 17562544 | Nordihydroguaiaretic acid (NDGA), an inhibitor of the HER2 and IGF-1 receptor tyrosine kinases, blocks the growth of HER2-overexpressing human breast cancer cells. |
| 1007 | 17562544 | We have reported that nordihydroguaiaretic acid (NDGA) inhibits the tyrosine kinase activities of the IGF-1 receptor (IGF-1R) and the HER2 receptor in breast cancer cells. |
| 1008 | 17562544 | NDGA inhibited both IGF-1R and HER2 kinase activities in these breast cancer cells. |
| 1009 | 17562544 | In contrast, Gefitinib, an epidermal growth factor receptor inhibitor but not an IGF-1R inhibitor, was more effective in MCF-7/HER2-18 cells than in the parental MCF-7 cells and IGF binding protein-3 (IGFBP-3) was more effective against MCF-7 cells compared to MCF-7/HER2-18. |
| 1010 | 17562544 | Nordihydroguaiaretic acid (NDGA), an inhibitor of the HER2 and IGF-1 receptor tyrosine kinases, blocks the growth of HER2-overexpressing human breast cancer cells. |
| 1011 | 17562544 | We have reported that nordihydroguaiaretic acid (NDGA) inhibits the tyrosine kinase activities of the IGF-1 receptor (IGF-1R) and the HER2 receptor in breast cancer cells. |
| 1012 | 17562544 | NDGA inhibited both IGF-1R and HER2 kinase activities in these breast cancer cells. |
| 1013 | 17562544 | In contrast, Gefitinib, an epidermal growth factor receptor inhibitor but not an IGF-1R inhibitor, was more effective in MCF-7/HER2-18 cells than in the parental MCF-7 cells and IGF binding protein-3 (IGFBP-3) was more effective against MCF-7 cells compared to MCF-7/HER2-18. |
| 1014 | 17562544 | Nordihydroguaiaretic acid (NDGA), an inhibitor of the HER2 and IGF-1 receptor tyrosine kinases, blocks the growth of HER2-overexpressing human breast cancer cells. |
| 1015 | 17562544 | We have reported that nordihydroguaiaretic acid (NDGA) inhibits the tyrosine kinase activities of the IGF-1 receptor (IGF-1R) and the HER2 receptor in breast cancer cells. |
| 1016 | 17562544 | NDGA inhibited both IGF-1R and HER2 kinase activities in these breast cancer cells. |
| 1017 | 17562544 | In contrast, Gefitinib, an epidermal growth factor receptor inhibitor but not an IGF-1R inhibitor, was more effective in MCF-7/HER2-18 cells than in the parental MCF-7 cells and IGF binding protein-3 (IGFBP-3) was more effective against MCF-7 cells compared to MCF-7/HER2-18. |
| 1018 | 17596523 | Diabetic nephropathy (DN) is associated with increased oxidative stress, overexpression and activation of growth factor receptors, including those for transforming growth factor-beta1 (TGF-beta-RII), platelet-derived growth factor (PDGF-R), and insulin-like growth factor (IGF1-R). |
| 1019 | 17596523 | The early phase of diabetes was found to be associated with an increase in glomerular expression of IGF1-R, PDGF-R, and TGF-beta-RII and activation of IRS1, Erk 1/2, and Smad 2/3. |
| 1020 | 17596523 | Diabetic nephropathy (DN) is associated with increased oxidative stress, overexpression and activation of growth factor receptors, including those for transforming growth factor-beta1 (TGF-beta-RII), platelet-derived growth factor (PDGF-R), and insulin-like growth factor (IGF1-R). |
| 1021 | 17596523 | The early phase of diabetes was found to be associated with an increase in glomerular expression of IGF1-R, PDGF-R, and TGF-beta-RII and activation of IRS1, Erk 1/2, and Smad 2/3. |
| 1022 | 17686258 | [The relationship of blood glucose and the expression of insulin-like growth factor-1 receptor mRNA in diabetic cardiomyopathy: a preliminary study with rats]. |
| 1023 | 17709881 | Both IGF-I and its receptor (IGF-IR) are specifically expressed in various cell types of the endocrine pancreas. |
| 1024 | 17709881 | For instance, combined inactivation of insulin receptor and IGF-IR or IGF-I and IGF-II genes in early embryos results in no defect on islet cell development; islet beta-cell-specific inactivation of IGF-IR gene causes no change in beta-cell mass; liver- and pancreatic-specific IGF-I gene deficiency (LID and PID mice) suggests that IGF-I exerts an inhibitory effect on islet cell growth albeit indirectly through controlling growth hormone release or expression of Reg family genes. |
| 1025 | 17709881 | Rather, it is probably a negative regulator through controlling growth hormone and insulin release, hyperglycemia, or Reg gene expression. |
| 1026 | 17709881 | Both IGF-I and its receptor (IGF-IR) are specifically expressed in various cell types of the endocrine pancreas. |
| 1027 | 17709881 | For instance, combined inactivation of insulin receptor and IGF-IR or IGF-I and IGF-II genes in early embryos results in no defect on islet cell development; islet beta-cell-specific inactivation of IGF-IR gene causes no change in beta-cell mass; liver- and pancreatic-specific IGF-I gene deficiency (LID and PID mice) suggests that IGF-I exerts an inhibitory effect on islet cell growth albeit indirectly through controlling growth hormone release or expression of Reg family genes. |
| 1028 | 17709881 | Rather, it is probably a negative regulator through controlling growth hormone and insulin release, hyperglycemia, or Reg gene expression. |
| 1029 | 18393172 | Mitogenic effect of the insulin analogue glargine in malignant cells in comparison with insulin and IGF-I. |
| 1030 | 18393172 | The aim of the study was to investigate if the insulin analogue glargine, with an increased affinity for the IGF-I receptor (IGF-IR), affects the cell growth to a larger extent than human insulin in malignant cells expressing IGF-IRs. |
| 1031 | 18393172 | The gene expression of insulin receptor (IR) varied between 4.3-7.5 x 10(-3) and the expression of IGF-IR between 7.7-147.7 x 10(-3) in relation to GAPDH (glyceraldehyde-3-phosphate dehydrogenase). |
| 1032 | 18393172 | Insulin receptor and IGF-IR protein varied between 2.0-4.1 ng/mg protein and 2.0-40.4 ng/mg protein, respectively. |
| 1033 | 18393172 | The IGF-IR was phosphorylated by IGF-I at a concentration of 10(-10)-10(-9) M. |
| 1034 | 18393172 | SaOS-2 cells were more sensitive to IGF-I than to insulin and glargine. |
| 1035 | 18393172 | MCF-7 cells were more sensitive to des(1-3)IGF-I than to IGF-I. |
| 1036 | 18393172 | Mitogenic effect of the insulin analogue glargine in malignant cells in comparison with insulin and IGF-I. |
| 1037 | 18393172 | The aim of the study was to investigate if the insulin analogue glargine, with an increased affinity for the IGF-I receptor (IGF-IR), affects the cell growth to a larger extent than human insulin in malignant cells expressing IGF-IRs. |
| 1038 | 18393172 | The gene expression of insulin receptor (IR) varied between 4.3-7.5 x 10(-3) and the expression of IGF-IR between 7.7-147.7 x 10(-3) in relation to GAPDH (glyceraldehyde-3-phosphate dehydrogenase). |
| 1039 | 18393172 | Insulin receptor and IGF-IR protein varied between 2.0-4.1 ng/mg protein and 2.0-40.4 ng/mg protein, respectively. |
| 1040 | 18393172 | The IGF-IR was phosphorylated by IGF-I at a concentration of 10(-10)-10(-9) M. |
| 1041 | 18393172 | SaOS-2 cells were more sensitive to IGF-I than to insulin and glargine. |
| 1042 | 18393172 | MCF-7 cells were more sensitive to des(1-3)IGF-I than to IGF-I. |
| 1043 | 18393172 | Mitogenic effect of the insulin analogue glargine in malignant cells in comparison with insulin and IGF-I. |
| 1044 | 18393172 | The aim of the study was to investigate if the insulin analogue glargine, with an increased affinity for the IGF-I receptor (IGF-IR), affects the cell growth to a larger extent than human insulin in malignant cells expressing IGF-IRs. |
| 1045 | 18393172 | The gene expression of insulin receptor (IR) varied between 4.3-7.5 x 10(-3) and the expression of IGF-IR between 7.7-147.7 x 10(-3) in relation to GAPDH (glyceraldehyde-3-phosphate dehydrogenase). |
| 1046 | 18393172 | Insulin receptor and IGF-IR protein varied between 2.0-4.1 ng/mg protein and 2.0-40.4 ng/mg protein, respectively. |
| 1047 | 18393172 | The IGF-IR was phosphorylated by IGF-I at a concentration of 10(-10)-10(-9) M. |
| 1048 | 18393172 | SaOS-2 cells were more sensitive to IGF-I than to insulin and glargine. |
| 1049 | 18393172 | MCF-7 cells were more sensitive to des(1-3)IGF-I than to IGF-I. |
| 1050 | 18393172 | Mitogenic effect of the insulin analogue glargine in malignant cells in comparison with insulin and IGF-I. |
| 1051 | 18393172 | The aim of the study was to investigate if the insulin analogue glargine, with an increased affinity for the IGF-I receptor (IGF-IR), affects the cell growth to a larger extent than human insulin in malignant cells expressing IGF-IRs. |
| 1052 | 18393172 | The gene expression of insulin receptor (IR) varied between 4.3-7.5 x 10(-3) and the expression of IGF-IR between 7.7-147.7 x 10(-3) in relation to GAPDH (glyceraldehyde-3-phosphate dehydrogenase). |
| 1053 | 18393172 | Insulin receptor and IGF-IR protein varied between 2.0-4.1 ng/mg protein and 2.0-40.4 ng/mg protein, respectively. |
| 1054 | 18393172 | The IGF-IR was phosphorylated by IGF-I at a concentration of 10(-10)-10(-9) M. |
| 1055 | 18393172 | SaOS-2 cells were more sensitive to IGF-I than to insulin and glargine. |
| 1056 | 18393172 | MCF-7 cells were more sensitive to des(1-3)IGF-I than to IGF-I. |
| 1057 | 18566589 | Small-molecule inhibition and activation-loop trans-phosphorylation of the IGF1 receptor. |
| 1058 | 18566589 | The insulin-like growth factor-1 receptor (IGF1R) is a receptor tyrosine kinase (RTK) that has a critical role in mitogenic signalling during embryogenesis and an antiapoptotic role in the survival and progression of many human tumours. |
| 1059 | 18566589 | Small-molecule inhibition and activation-loop trans-phosphorylation of the IGF1 receptor. |
| 1060 | 18566589 | The insulin-like growth factor-1 receptor (IGF1R) is a receptor tyrosine kinase (RTK) that has a critical role in mitogenic signalling during embryogenesis and an antiapoptotic role in the survival and progression of many human tumours. |
| 1061 | 18676006 | Immunolocalization of insulin-like growth factors and their receptors in the diabetic mouse oviduct and uterine tissues during the preimplantation period. |
| 1062 | 18676006 | The aim of the present study was to analyze the immunolocalization of insulin-like growth factor (IGF)-1 and IGF-2 and their receptors in the oviduct and uterus of control and diabetic mice. |
| 1063 | 18676006 | Localization of IGF-1, IGF-2, IGF-1R and IGF-2R was determined by immunohistochemistry and a semi-quantitative scoring of immunolabelling was performed using a standardized 5-point system. |
| 1064 | 18676006 | The immunohistochemical scorings for both IGF-1 and IGF-1R were significantly decreased in the oviducts of diabetic mice at 96 h post-hCG treatment. |
| 1065 | 18676006 | The scores for IGF-2 were significantly increased in the oviducts of diabetic mice at 48 and 72 h post-hCG treatment, and for IGF-2R at 72 h post-hCG treatment. |
| 1066 | 18676006 | Immunolocalization of insulin-like growth factors and their receptors in the diabetic mouse oviduct and uterine tissues during the preimplantation period. |
| 1067 | 18676006 | The aim of the present study was to analyze the immunolocalization of insulin-like growth factor (IGF)-1 and IGF-2 and their receptors in the oviduct and uterus of control and diabetic mice. |
| 1068 | 18676006 | Localization of IGF-1, IGF-2, IGF-1R and IGF-2R was determined by immunohistochemistry and a semi-quantitative scoring of immunolabelling was performed using a standardized 5-point system. |
| 1069 | 18676006 | The immunohistochemical scorings for both IGF-1 and IGF-1R were significantly decreased in the oviducts of diabetic mice at 96 h post-hCG treatment. |
| 1070 | 18676006 | The scores for IGF-2 were significantly increased in the oviducts of diabetic mice at 48 and 72 h post-hCG treatment, and for IGF-2R at 72 h post-hCG treatment. |
| 1071 | 18924581 | The effect of 40% food restriction (FR) and replenishment on the growth hormone (GH) and insulin-like growth factor-I (IGF-I) axis in the epiphyseal growth plate (EGP) was examined in a mouse model. |
| 1072 | 18924581 | Changes in RNA and protein levels were evaluated with real time PCR and immunohistochemistry, respectively, and serum levels of IGF-I and leptin were measured with radioimmunoassay. |
| 1073 | 18924581 | The protein levels of IGF-I receptor (IGF-IR) and GH receptor (GHR), which were reduced during FR, increased during catch-up growth without an apparent change in the level of their RNA. |
| 1074 | 18924581 | Serum IGF-I and leptin levels were reduced during FR and increased during catch-up growth. |
| 1075 | 18924581 | Following 40% FR, there was a significant decrease in the level of GHR and IGF-IR in the EGP which may explain the reduced effect of GH treatment in malnourished animals and children. |
| 1076 | 18924581 | The effect of 40% food restriction (FR) and replenishment on the growth hormone (GH) and insulin-like growth factor-I (IGF-I) axis in the epiphyseal growth plate (EGP) was examined in a mouse model. |
| 1077 | 18924581 | Changes in RNA and protein levels were evaluated with real time PCR and immunohistochemistry, respectively, and serum levels of IGF-I and leptin were measured with radioimmunoassay. |
| 1078 | 18924581 | The protein levels of IGF-I receptor (IGF-IR) and GH receptor (GHR), which were reduced during FR, increased during catch-up growth without an apparent change in the level of their RNA. |
| 1079 | 18924581 | Serum IGF-I and leptin levels were reduced during FR and increased during catch-up growth. |
| 1080 | 18924581 | Following 40% FR, there was a significant decrease in the level of GHR and IGF-IR in the EGP which may explain the reduced effect of GH treatment in malnourished animals and children. |
| 1081 | 19001411 | The phosphotyrosine interactome of the insulin receptor family and its substrates IRS-1 and IRS-2. |
| 1082 | 19001411 | We targeted and compared insulin receptor substrates 1 and 2 (IRS-1 and IRS-2) as central distributors of the insulin signal, the insulin receptor, the insulin-like growth factor 1 receptor, and the insulin receptor-related receptor. |
| 1083 | 19001411 | Our results retrieve known interactions and substantially broaden the spectrum of potential interaction partners of IRS-1 and IRS-2. |
| 1084 | 19001411 | However, several proteins involved in signaling and metabolism interact differentially with IRS-1 and IRS-2 and thus provide leads into their different physiological roles. |
| 1085 | 19001411 | Differences in interactions at the receptor level are reflected in multisite recruitment of SHP2 by the insulin-like growth factor 1 receptor and limited but exclusive interactions with the IRR. |
| 1086 | 19001411 | The phosphotyrosine interactome of the insulin receptor family and its substrates IRS-1 and IRS-2. |
| 1087 | 19001411 | We targeted and compared insulin receptor substrates 1 and 2 (IRS-1 and IRS-2) as central distributors of the insulin signal, the insulin receptor, the insulin-like growth factor 1 receptor, and the insulin receptor-related receptor. |
| 1088 | 19001411 | Our results retrieve known interactions and substantially broaden the spectrum of potential interaction partners of IRS-1 and IRS-2. |
| 1089 | 19001411 | However, several proteins involved in signaling and metabolism interact differentially with IRS-1 and IRS-2 and thus provide leads into their different physiological roles. |
| 1090 | 19001411 | Differences in interactions at the receptor level are reflected in multisite recruitment of SHP2 by the insulin-like growth factor 1 receptor and limited but exclusive interactions with the IRR. |
| 1091 | 19008912 | Insulin regulates SOCS2 expression and the mitogenic effect of IGF-1 in mesangial cells. |
| 1092 | 19008912 | Using DNA microarray analysis of glomerular RNA from control and diabetic rats we found that the expression levels of insulin-like growth factor 1 receptor (IGF-1R) were increased while those of suppressor of cytokine signaling 2 (SOCS2) and STAT5 were decreased. |
| 1093 | 19008912 | Overexpression of SOCS2 in rat mesangial cells inhibited IGF-1-induced activation of extracellular signal-regulated kinase, which subsequently reduced type IV collagen and DNA synthesis, an effect due to interaction of SOCS2 with IGF-1R. |
| 1094 | 19008912 | Inhibition of SOCS2 overexpression by small interfering RNA suppressed IGF-1R-mediated actions by preventing phosphorylation of tyrosine 317 in the p66Shc adaptor protein; however, overexpression of either SOCS1 or SOCS3 did not affect IGF-1R signaling. |
| 1095 | 19008912 | Insulin directly increased STAT5 and SOCS2 expression in mesangial cells. |
| 1096 | 19008912 | This study shows that insulin can inhibit the mitogenic action of IGF-1 in mesangial cells by regulating STAT5/SOCS2 expression. |
| 1097 | 19008912 | Insulin deficiency may contribute to the mesangial expansion found in diabetes through reduced STAT5/SOCS2 expression. |
| 1098 | 19008912 | Insulin regulates SOCS2 expression and the mitogenic effect of IGF-1 in mesangial cells. |
| 1099 | 19008912 | Using DNA microarray analysis of glomerular RNA from control and diabetic rats we found that the expression levels of insulin-like growth factor 1 receptor (IGF-1R) were increased while those of suppressor of cytokine signaling 2 (SOCS2) and STAT5 were decreased. |
| 1100 | 19008912 | Overexpression of SOCS2 in rat mesangial cells inhibited IGF-1-induced activation of extracellular signal-regulated kinase, which subsequently reduced type IV collagen and DNA synthesis, an effect due to interaction of SOCS2 with IGF-1R. |
| 1101 | 19008912 | Inhibition of SOCS2 overexpression by small interfering RNA suppressed IGF-1R-mediated actions by preventing phosphorylation of tyrosine 317 in the p66Shc adaptor protein; however, overexpression of either SOCS1 or SOCS3 did not affect IGF-1R signaling. |
| 1102 | 19008912 | Insulin directly increased STAT5 and SOCS2 expression in mesangial cells. |
| 1103 | 19008912 | This study shows that insulin can inhibit the mitogenic action of IGF-1 in mesangial cells by regulating STAT5/SOCS2 expression. |
| 1104 | 19008912 | Insulin deficiency may contribute to the mesangial expansion found in diabetes through reduced STAT5/SOCS2 expression. |
| 1105 | 19008912 | Insulin regulates SOCS2 expression and the mitogenic effect of IGF-1 in mesangial cells. |
| 1106 | 19008912 | Using DNA microarray analysis of glomerular RNA from control and diabetic rats we found that the expression levels of insulin-like growth factor 1 receptor (IGF-1R) were increased while those of suppressor of cytokine signaling 2 (SOCS2) and STAT5 were decreased. |
| 1107 | 19008912 | Overexpression of SOCS2 in rat mesangial cells inhibited IGF-1-induced activation of extracellular signal-regulated kinase, which subsequently reduced type IV collagen and DNA synthesis, an effect due to interaction of SOCS2 with IGF-1R. |
| 1108 | 19008912 | Inhibition of SOCS2 overexpression by small interfering RNA suppressed IGF-1R-mediated actions by preventing phosphorylation of tyrosine 317 in the p66Shc adaptor protein; however, overexpression of either SOCS1 or SOCS3 did not affect IGF-1R signaling. |
| 1109 | 19008912 | Insulin directly increased STAT5 and SOCS2 expression in mesangial cells. |
| 1110 | 19008912 | This study shows that insulin can inhibit the mitogenic action of IGF-1 in mesangial cells by regulating STAT5/SOCS2 expression. |
| 1111 | 19008912 | Insulin deficiency may contribute to the mesangial expansion found in diabetes through reduced STAT5/SOCS2 expression. |
| 1112 | 19122171 | Insulin-like growth factor-1 receptor expression masks the antiinflammatory and glucose uptake capacity of insulin in vascular smooth muscle cells. |
| 1113 | 19138973 | The activation of the insulin-like growth factor (IGF)/IGF-IR axis plays a critical role in this carcinogenesis. (-)-Epigallocatechin gallate (EGCG), the major constituent of green tea, seems to have both antiobesity and antidiabetic effects. |
| 1114 | 19138973 | At sacrifice, drinking water with EGCG caused a significant decrease in the number of total aberrant crypt foci, large aberrant crypt foci, and beta-catenin accumulated crypts in these mice, all of which are premalignant lesions of the colon. |
| 1115 | 19138973 | The colonic mucosa of db/db mice expressed high levels of the IGF-IR, phosphorylated form of IGF-IR (p-IGF-IR), p-GSK-3beta, beta-catenin, cyclooxygenase-2, and cyclin D1 proteins, and EGCG in drinking water caused a marked decrease in the expression of these proteins. |
| 1116 | 19138973 | Treating these mice with EGCG also caused an increase in the serum level of IGFBP-3 while conversely decreasing the serum levels of IGF-I, insulin, triglyceride, cholesterol, and leptin. |
| 1117 | 19138973 | The activation of the insulin-like growth factor (IGF)/IGF-IR axis plays a critical role in this carcinogenesis. (-)-Epigallocatechin gallate (EGCG), the major constituent of green tea, seems to have both antiobesity and antidiabetic effects. |
| 1118 | 19138973 | At sacrifice, drinking water with EGCG caused a significant decrease in the number of total aberrant crypt foci, large aberrant crypt foci, and beta-catenin accumulated crypts in these mice, all of which are premalignant lesions of the colon. |
| 1119 | 19138973 | The colonic mucosa of db/db mice expressed high levels of the IGF-IR, phosphorylated form of IGF-IR (p-IGF-IR), p-GSK-3beta, beta-catenin, cyclooxygenase-2, and cyclin D1 proteins, and EGCG in drinking water caused a marked decrease in the expression of these proteins. |
| 1120 | 19138973 | Treating these mice with EGCG also caused an increase in the serum level of IGFBP-3 while conversely decreasing the serum levels of IGF-I, insulin, triglyceride, cholesterol, and leptin. |
| 1121 | 19387875 | Increased renal Akt/mTOR and MAPK signaling in type I diabetes in the absence of IGF type 1 receptor activation. |
| 1122 | 19387875 | We investigated renal GH receptor (GHR) and IGF-type 1 receptor (IGF1R) signaling in an animal model of type I DM. |
| 1123 | 19387875 | Kidney tissue was examined for GHR and IGF1R key signaling molecules. |
| 1124 | 19387875 | GHR levels were unchanged and IGF-I mRNA levels were decreased in the diabetic group (D). |
| 1125 | 19387875 | Basal and GH stimulated phosphorylated (p-) JAK2 and STAT5 levels were similar in controls (C) and D. |
| 1126 | 19387875 | On the other hand while IGF1R phosphorylation was unchanged, Akt/mTOR and MAPK signaling were hyperactivate in DM, suggesting their involvement. |
| 1127 | 19387875 | The increase in baseline activated Akt, mTOR, rpS6, and MAPK cannot be explained by activation of the IGF1R, but may be triggered by other growth factors and nutrients. |
| 1128 | 19387875 | Increased renal Akt/mTOR and MAPK signaling in type I diabetes in the absence of IGF type 1 receptor activation. |
| 1129 | 19387875 | We investigated renal GH receptor (GHR) and IGF-type 1 receptor (IGF1R) signaling in an animal model of type I DM. |
| 1130 | 19387875 | Kidney tissue was examined for GHR and IGF1R key signaling molecules. |
| 1131 | 19387875 | GHR levels were unchanged and IGF-I mRNA levels were decreased in the diabetic group (D). |
| 1132 | 19387875 | Basal and GH stimulated phosphorylated (p-) JAK2 and STAT5 levels were similar in controls (C) and D. |
| 1133 | 19387875 | On the other hand while IGF1R phosphorylation was unchanged, Akt/mTOR and MAPK signaling were hyperactivate in DM, suggesting their involvement. |
| 1134 | 19387875 | The increase in baseline activated Akt, mTOR, rpS6, and MAPK cannot be explained by activation of the IGF1R, but may be triggered by other growth factors and nutrients. |
| 1135 | 19387875 | Increased renal Akt/mTOR and MAPK signaling in type I diabetes in the absence of IGF type 1 receptor activation. |
| 1136 | 19387875 | We investigated renal GH receptor (GHR) and IGF-type 1 receptor (IGF1R) signaling in an animal model of type I DM. |
| 1137 | 19387875 | Kidney tissue was examined for GHR and IGF1R key signaling molecules. |
| 1138 | 19387875 | GHR levels were unchanged and IGF-I mRNA levels were decreased in the diabetic group (D). |
| 1139 | 19387875 | Basal and GH stimulated phosphorylated (p-) JAK2 and STAT5 levels were similar in controls (C) and D. |
| 1140 | 19387875 | On the other hand while IGF1R phosphorylation was unchanged, Akt/mTOR and MAPK signaling were hyperactivate in DM, suggesting their involvement. |
| 1141 | 19387875 | The increase in baseline activated Akt, mTOR, rpS6, and MAPK cannot be explained by activation of the IGF1R, but may be triggered by other growth factors and nutrients. |
| 1142 | 19387875 | Increased renal Akt/mTOR and MAPK signaling in type I diabetes in the absence of IGF type 1 receptor activation. |
| 1143 | 19387875 | We investigated renal GH receptor (GHR) and IGF-type 1 receptor (IGF1R) signaling in an animal model of type I DM. |
| 1144 | 19387875 | Kidney tissue was examined for GHR and IGF1R key signaling molecules. |
| 1145 | 19387875 | GHR levels were unchanged and IGF-I mRNA levels were decreased in the diabetic group (D). |
| 1146 | 19387875 | Basal and GH stimulated phosphorylated (p-) JAK2 and STAT5 levels were similar in controls (C) and D. |
| 1147 | 19387875 | On the other hand while IGF1R phosphorylation was unchanged, Akt/mTOR and MAPK signaling were hyperactivate in DM, suggesting their involvement. |
| 1148 | 19387875 | The increase in baseline activated Akt, mTOR, rpS6, and MAPK cannot be explained by activation of the IGF1R, but may be triggered by other growth factors and nutrients. |
| 1149 | 19406106 | Insulin-like growth factor-1 receptor activation prevents high glucose-induced mitochondrial dysfunction, cytochrome-c release and apoptosis. |
| 1150 | 19406106 | Addition of IGF-1 blocked the high glucose effect in a manner dependent on expression of IGF-1 receptor (IGF-1R) since silencing IGF-1R with small interference RNA could diminish the IGF-1' anti-apoptosis effect. |
| 1151 | 19406106 | Our findings show that enhanced IGF-1 signaling inhibits glucose-induced apoptosis in HUVECs by reducing mitochondrial dysfunction, and maintaining the mitochondrial retention of cytochrome-c. |
| 1152 | 19406106 | Insulin-like growth factor-1 receptor activation prevents high glucose-induced mitochondrial dysfunction, cytochrome-c release and apoptosis. |
| 1153 | 19406106 | Addition of IGF-1 blocked the high glucose effect in a manner dependent on expression of IGF-1 receptor (IGF-1R) since silencing IGF-1R with small interference RNA could diminish the IGF-1' anti-apoptosis effect. |
| 1154 | 19406106 | Our findings show that enhanced IGF-1 signaling inhibits glucose-induced apoptosis in HUVECs by reducing mitochondrial dysfunction, and maintaining the mitochondrial retention of cytochrome-c. |
| 1155 | 19467150 | In maternal diabetes, components of this system including insulin, IGF1, IGF2 and various IGF-binding proteins are deregulated in the maternal or fetal circulation, or in the placenta. |
| 1156 | 19467150 | The placenta expresses considerable amounts of insulin and IGF1 receptors at distinct locations on both placental surfaces. |
| 1157 | 19467150 | This makes the insulin and the IGF1 receptor accessible to fetal and/or maternal insulin, IGF1 and IGF2. |
| 1158 | 19467150 | Unlike the receptor for IGF1, the insulin receptor undergoes a gestational change in expression site from the trophoblast at the beginning of pregnancy to the endothelium at term. |
| 1159 | 19472218 | Phospholipid transfer protein reduces phosphorylation of tau in human neuronal cells. |
| 1160 | 19472218 | In this study we provide evidence that phospholipid transfer protein (PLTP), one of the main lipid transfer proteins in the brain, significantly reduces levels of phosphorylated tau and increases levels of the inactive form of glycogen synthase kinase-3beta (GSK3 beta) in HCN2 cells. |
| 1161 | 19472218 | Furthermore, inhibition of phosphatidylinositol-3 kinase (PI3K) reversed the PLTP-induced increase in levels of GSK3 beta phosphorylated at serine 9 (pGSK3 beta(Ser9)) and partially reversed the PLTP-induced reduction in tau phosphorylation. |
| 1162 | 19472218 | We provide evidence that the PLTP-induced changes are not due to activation of Disabled-1 (Dab1), insofar as PLTP reduced levels of total and phosphorylated Dab1 in HCN2 cells. |
| 1163 | 19472218 | We have also shown that inhibition of tyrosine kinase activity of insulin receptor (IR) and/or insulin-like growth factor 1 (IGF1) receptor (IGFR) reverses the PLTP-induced increase in levels of phosphorylated Akt (pAkt(Thr308) and pAkt(Ser473)), suggesting that PLTP-mediated activation of the PI3K/Akt pathway is dependent on IR/IGFR receptor tyrosine kinase activity. |
| 1164 | 19477944 | Unraveling insulin-like growth factor binding protein-3 actions in human disease. |
| 1165 | 19477944 | Interestingly, apart from the ability to inhibit or enhance IGF actions, IGFBP-3 also exhibits very clear, distinct biological effects independent of the IGF/IGF-I receptor axis. |
| 1166 | 19477944 | This review reinforces the concept in support of the IGF/IGF-IR axis-independent actions of IGFBP-3 and delineates potential underlying mechanisms involved and subsequent biological significance, focusing in particular on functional binding partners and the clinical significance of IGFBP-3 in the assessment of cancer risk. |
| 1167 | 19519303 | The role of IGF-1 receptor and insulin receptor signaling for the pathogenesis of Alzheimer's disease: from model organisms to human disease. |
| 1168 | 19519303 | Alternatively, the mechanism might be directly related to insulin and insulin-like growth factor(IGF)-1 signaling, leading to the proposal that AD is a "brain-type diabetes". |
| 1169 | 19519303 | Furthermore, postmortem analyses of brains from patients with AD revealed a markedly downregulated expression of insulin receptor (IR), IGF-1 receptor (IGF-1R), insulin receptor substrate (IRS)-1 and IRS-2, and these changes progress with severity of neurodegeneration. |
| 1170 | 19519303 | Recently, Cohen and coworkers have show that knocking down DAF-2 in C. elegans, the homolog of the mammalian IR/IGF-1R, reduces beta-amyloid(Abeta)(1-42) toxicity. |
| 1171 | 19519303 | Cell based experiments suggest a specific role for the IGF 1/IRS-2 signaling pathway in regulating alpha-/beta-secretase activity. |
| 1172 | 19519303 | Moreover circulating IGF-1 might influence Abeta clearance from the brain by promoting Abeta transport over the blood brain barrier. |
| 1173 | 19519303 | Interestingly, brain specific deletion of IRS-2 increases life span, suggesting that long term neuronal IGF-1R signaling might be harmful. |
| 1174 | 19519303 | Taken together, the data from humans and different model organisms indicate a role of IR/IGF-1R signaling in Abeta metabolism, and clearance as well as longevity. |
| 1175 | 19519303 | Since more studies are needed to elucidate the impact of insulin and/or IGF-1 treatment in AD, the time to propose these hormones as a potential treatment option for AD has not come yet. |
| 1176 | 19519303 | The role of IGF-1 receptor and insulin receptor signaling for the pathogenesis of Alzheimer's disease: from model organisms to human disease. |
| 1177 | 19519303 | Alternatively, the mechanism might be directly related to insulin and insulin-like growth factor(IGF)-1 signaling, leading to the proposal that AD is a "brain-type diabetes". |
| 1178 | 19519303 | Furthermore, postmortem analyses of brains from patients with AD revealed a markedly downregulated expression of insulin receptor (IR), IGF-1 receptor (IGF-1R), insulin receptor substrate (IRS)-1 and IRS-2, and these changes progress with severity of neurodegeneration. |
| 1179 | 19519303 | Recently, Cohen and coworkers have show that knocking down DAF-2 in C. elegans, the homolog of the mammalian IR/IGF-1R, reduces beta-amyloid(Abeta)(1-42) toxicity. |
| 1180 | 19519303 | Cell based experiments suggest a specific role for the IGF 1/IRS-2 signaling pathway in regulating alpha-/beta-secretase activity. |
| 1181 | 19519303 | Moreover circulating IGF-1 might influence Abeta clearance from the brain by promoting Abeta transport over the blood brain barrier. |
| 1182 | 19519303 | Interestingly, brain specific deletion of IRS-2 increases life span, suggesting that long term neuronal IGF-1R signaling might be harmful. |
| 1183 | 19519303 | Taken together, the data from humans and different model organisms indicate a role of IR/IGF-1R signaling in Abeta metabolism, and clearance as well as longevity. |
| 1184 | 19519303 | Since more studies are needed to elucidate the impact of insulin and/or IGF-1 treatment in AD, the time to propose these hormones as a potential treatment option for AD has not come yet. |
| 1185 | 19519303 | The role of IGF-1 receptor and insulin receptor signaling for the pathogenesis of Alzheimer's disease: from model organisms to human disease. |
| 1186 | 19519303 | Alternatively, the mechanism might be directly related to insulin and insulin-like growth factor(IGF)-1 signaling, leading to the proposal that AD is a "brain-type diabetes". |
| 1187 | 19519303 | Furthermore, postmortem analyses of brains from patients with AD revealed a markedly downregulated expression of insulin receptor (IR), IGF-1 receptor (IGF-1R), insulin receptor substrate (IRS)-1 and IRS-2, and these changes progress with severity of neurodegeneration. |
| 1188 | 19519303 | Recently, Cohen and coworkers have show that knocking down DAF-2 in C. elegans, the homolog of the mammalian IR/IGF-1R, reduces beta-amyloid(Abeta)(1-42) toxicity. |
| 1189 | 19519303 | Cell based experiments suggest a specific role for the IGF 1/IRS-2 signaling pathway in regulating alpha-/beta-secretase activity. |
| 1190 | 19519303 | Moreover circulating IGF-1 might influence Abeta clearance from the brain by promoting Abeta transport over the blood brain barrier. |
| 1191 | 19519303 | Interestingly, brain specific deletion of IRS-2 increases life span, suggesting that long term neuronal IGF-1R signaling might be harmful. |
| 1192 | 19519303 | Taken together, the data from humans and different model organisms indicate a role of IR/IGF-1R signaling in Abeta metabolism, and clearance as well as longevity. |
| 1193 | 19519303 | Since more studies are needed to elucidate the impact of insulin and/or IGF-1 treatment in AD, the time to propose these hormones as a potential treatment option for AD has not come yet. |
| 1194 | 19519303 | The role of IGF-1 receptor and insulin receptor signaling for the pathogenesis of Alzheimer's disease: from model organisms to human disease. |
| 1195 | 19519303 | Alternatively, the mechanism might be directly related to insulin and insulin-like growth factor(IGF)-1 signaling, leading to the proposal that AD is a "brain-type diabetes". |
| 1196 | 19519303 | Furthermore, postmortem analyses of brains from patients with AD revealed a markedly downregulated expression of insulin receptor (IR), IGF-1 receptor (IGF-1R), insulin receptor substrate (IRS)-1 and IRS-2, and these changes progress with severity of neurodegeneration. |
| 1197 | 19519303 | Recently, Cohen and coworkers have show that knocking down DAF-2 in C. elegans, the homolog of the mammalian IR/IGF-1R, reduces beta-amyloid(Abeta)(1-42) toxicity. |
| 1198 | 19519303 | Cell based experiments suggest a specific role for the IGF 1/IRS-2 signaling pathway in regulating alpha-/beta-secretase activity. |
| 1199 | 19519303 | Moreover circulating IGF-1 might influence Abeta clearance from the brain by promoting Abeta transport over the blood brain barrier. |
| 1200 | 19519303 | Interestingly, brain specific deletion of IRS-2 increases life span, suggesting that long term neuronal IGF-1R signaling might be harmful. |
| 1201 | 19519303 | Taken together, the data from humans and different model organisms indicate a role of IR/IGF-1R signaling in Abeta metabolism, and clearance as well as longevity. |
| 1202 | 19519303 | Since more studies are needed to elucidate the impact of insulin and/or IGF-1 treatment in AD, the time to propose these hormones as a potential treatment option for AD has not come yet. |
| 1203 | 19589910 | Human aortic smooth muscle cells are insulin resistant at the receptor level but sensitive to IGF1 and IGF2. |
| 1204 | 19589910 | For comparison, the effects of IGF1 and IGF2 were also studied. |
| 1205 | 19589910 | In HASMC, both mRNA and protein expression of IGF1 receptors (IGF1R) were fivefold higher compared to insulin receptor (IR). |
| 1206 | 19589910 | IGF1 stimulated IR substrate-1 and AKT at 10(-8) mol/l and extracellular signal-regulated kinases 1 and 2 at 10(-9)-10(-8) mol/l respectively. |
| 1207 | 19589910 | IGF1 and 2 at a concentration of 10(-8)-10(-7) mol/l significantly stimulated (3)H-thymidine incorporation, whereas insulin did not. (14)C-Glucose accumulation was stimulated by IGF1 or IGF2 10(-8)-10(-7) mol/l, and also by insulin 10(-7) mol/l. |
| 1208 | 19589910 | Our results suggest that IGF1R and hybrid IR/IGF1R are activated by physiological concentrations of IGF1 and 2 in HASMC and this propagates downstream signaling and biological effects, while insulin has no effect on its receptor or downstream signaling probably due to a preponderance of IGF1R and incorporation of IR into hybrid IR/IGF1R. |
| 1209 | 19617901 | Physical and functional interaction between polyoma virus middle T antigen and insulin and IGF-I receptors is required for oncogene activation and tumour initiation. |
| 1210 | 19617901 | The insulin-like growth factor I receptor (IGF-IR) and the insulin receptor (IR) are known to be implicated in the development of many cancers. |
| 1211 | 19617901 | Insulin and IGF-I increase association of the IR and IGF-IR with PyVmT, enhance tyrosine phosphorylation of PyVmT and augment the recruitment of Src and PLCgamma(1) to PyVmT. |
| 1212 | 19617901 | This is accompanied by robust and sustained phosphorylation of Akt and ERK1/2, which are implicated in both PyVmT and IGF-IR/IR signalling. |
| 1213 | 19617901 | Physical and functional interaction between polyoma virus middle T antigen and insulin and IGF-I receptors is required for oncogene activation and tumour initiation. |
| 1214 | 19617901 | The insulin-like growth factor I receptor (IGF-IR) and the insulin receptor (IR) are known to be implicated in the development of many cancers. |
| 1215 | 19617901 | Insulin and IGF-I increase association of the IR and IGF-IR with PyVmT, enhance tyrosine phosphorylation of PyVmT and augment the recruitment of Src and PLCgamma(1) to PyVmT. |
| 1216 | 19617901 | This is accompanied by robust and sustained phosphorylation of Akt and ERK1/2, which are implicated in both PyVmT and IGF-IR/IR signalling. |
| 1217 | 19617901 | Physical and functional interaction between polyoma virus middle T antigen and insulin and IGF-I receptors is required for oncogene activation and tumour initiation. |
| 1218 | 19617901 | The insulin-like growth factor I receptor (IGF-IR) and the insulin receptor (IR) are known to be implicated in the development of many cancers. |
| 1219 | 19617901 | Insulin and IGF-I increase association of the IR and IGF-IR with PyVmT, enhance tyrosine phosphorylation of PyVmT and augment the recruitment of Src and PLCgamma(1) to PyVmT. |
| 1220 | 19617901 | This is accompanied by robust and sustained phosphorylation of Akt and ERK1/2, which are implicated in both PyVmT and IGF-IR/IR signalling. |
| 1221 | 19628413 | With 11 mmol/L glucose, cellular proliferation, alkaline phosphatase (ALP) activity, the number of nodules formed, and calcium deposition in mineralized nodules were increased significantly; intracellular reactive oxygen species (ROS) and apoptosis were slightly reduced, although these reductions were not statistically significant. |
| 1222 | 19628413 | Moreover, we assessed the gene expression levels of Runx2, IGF-1, and IGF-1R. |
| 1223 | 19628413 | Eleven micromole per liter glucose stimulated Runx2 and IGF-1 expression; 44 mmol/L glucose inhibited Runx2, IGF-1, and IGF-1R expression. |
| 1224 | 19628413 | Metformin stimulated the expression of Runx2 and IGF-1 in three glucose groups, but it did not affect IGF-1R. |
| 1225 | 19628413 | Metformin not only significantly decreased intracellular ROS and apoptosis, but also had a direct osteogenic effect on osteoblasts at all glucose concentrations, which could be partially mediated via promotion of Runx2 and IGF-1 expression. |
| 1226 | 19628413 | With 11 mmol/L glucose, cellular proliferation, alkaline phosphatase (ALP) activity, the number of nodules formed, and calcium deposition in mineralized nodules were increased significantly; intracellular reactive oxygen species (ROS) and apoptosis were slightly reduced, although these reductions were not statistically significant. |
| 1227 | 19628413 | Moreover, we assessed the gene expression levels of Runx2, IGF-1, and IGF-1R. |
| 1228 | 19628413 | Eleven micromole per liter glucose stimulated Runx2 and IGF-1 expression; 44 mmol/L glucose inhibited Runx2, IGF-1, and IGF-1R expression. |
| 1229 | 19628413 | Metformin stimulated the expression of Runx2 and IGF-1 in three glucose groups, but it did not affect IGF-1R. |
| 1230 | 19628413 | Metformin not only significantly decreased intracellular ROS and apoptosis, but also had a direct osteogenic effect on osteoblasts at all glucose concentrations, which could be partially mediated via promotion of Runx2 and IGF-1 expression. |
| 1231 | 19680556 | We re-sequenced all exons, intron-exon boundaries and selected conserved non-coding sequences of candidate genes involved in aging-related processes, including dietary restriction (PPARG, PPARGC1A, SIRT1, SIRT3, UCP2, UCP3), metabolism (IGF1R, APOB, SCD), autophagy (BECN1, FRAP1), stem cell activation (NOTCH1, DLL1), tumor suppression (TP53, CDKN2A, ING1), DNA methylation (TRDMT1, DNMT3A, DNMT3B) Progeria syndromes (LMNA, ZMPSTE24, KL) and stress response (CRYAB, HSPB2). |
| 1232 | 19718675 | Cardiac mitochondrial-dependent apoptotic pathways, such as Bad, cytosolic cytochrome c, activated caspase 9 and 3, and calcineurin-nuclear factor activation transcription 3 (NFAT3) hypertrophic pathway in DM were increased compared to Control and attenuated in DI group after 8 weeks whereas those were not found after 4 weeks. |
| 1233 | 19718675 | Insulin-like growth factor-I receptor (IGFIR), phosphatidylinositol 3'-kinase (PI3K), and the protein kinase B (Akt) were significantly decreased in DM relative to Control and DI after 8 weeks whereas those were not found after 4 weeks. |
| 1234 | 19718675 | Insulin replacement not only prevents activation of the cardiac mitochondrial-dependent apoptotic pathway and calcineurin-related NFAT3 hypertrophic pathway in diabetes but it also enhances the cardiac insulin/IGFIR-PI3K-Akt survival pathway, all of which are attenuated with insulin therapeutic duration-dependent manners. |
| 1235 | 19718675 | Cardiac mitochondrial-dependent apoptotic pathways, such as Bad, cytosolic cytochrome c, activated caspase 9 and 3, and calcineurin-nuclear factor activation transcription 3 (NFAT3) hypertrophic pathway in DM were increased compared to Control and attenuated in DI group after 8 weeks whereas those were not found after 4 weeks. |
| 1236 | 19718675 | Insulin-like growth factor-I receptor (IGFIR), phosphatidylinositol 3'-kinase (PI3K), and the protein kinase B (Akt) were significantly decreased in DM relative to Control and DI after 8 weeks whereas those were not found after 4 weeks. |
| 1237 | 19718675 | Insulin replacement not only prevents activation of the cardiac mitochondrial-dependent apoptotic pathway and calcineurin-related NFAT3 hypertrophic pathway in diabetes but it also enhances the cardiac insulin/IGFIR-PI3K-Akt survival pathway, all of which are attenuated with insulin therapeutic duration-dependent manners. |
| 1238 | 19946718 | Cell-type-specific roles of IGF-1R and EGFR in mediating Zn2+-induced ERK1/2 and PKB phosphorylation. |
| 1239 | 19946718 | Zn(2+) exerts insulin-mimetic and antidiabetic effects in rodent models of insulin resistance, and activates extracellular-signal-regulated kinases 1 and 2 (ERK1/2) and protein kinase B (PKB), key components of the insulin signaling pathway. |
| 1240 | 19946718 | Zn(2+)-induced signaling has been shown to be associated with an increase in the tyrosine phosphorylation of insulin receptor (IR), as well as of insulin-like growth factor 1 receptor (IGF-1R) and epidermal growth factor receptor (EGFR) in several cell types. |
| 1241 | 19946718 | Therefore, using a series of pharmacological inhibitors and genetically engineered cells, we have investigated the roles of various R-PTKs in Zn(2+)-induced ERK1/2 and PKB phosphorylation. |
| 1242 | 19946718 | Pretreatment of Chinese hamster ovary (CHO) cells overexpressing a human IR (CHO-HIR cells) with AG1024, an inhibitor for IR protein tyrosine kinase (PTK) and IGF-1R-PTK, blocked Zn(2+)-induced ERK1/2 and PKB phosphorylation, but AG1478, an inhibitor for EGFR, was without effect in CHO cells. |
| 1243 | 19946718 | On the other hand, both of these inhibitors were able to attenuate Zn(2+)-induced phosphorylation of ERK1/2 and PKB in A10 vascular smooth muscle cells. |
| 1244 | 19946718 | Furthermore, both Zn(2+) and insulin-like growth factor 1 failed to stimulate ERK1/2 and PKB phosphorylation in IGF-1R knockout cells. |
| 1245 | 19946718 | Taken together, these data suggest that distinct R-PTKs mediate Zn(2+)-evoked ERK1/2 and PKB phosphorylation in a cell-specific manner. |
| 1246 | 19946718 | Cell-type-specific roles of IGF-1R and EGFR in mediating Zn2+-induced ERK1/2 and PKB phosphorylation. |
| 1247 | 19946718 | Zn(2+) exerts insulin-mimetic and antidiabetic effects in rodent models of insulin resistance, and activates extracellular-signal-regulated kinases 1 and 2 (ERK1/2) and protein kinase B (PKB), key components of the insulin signaling pathway. |
| 1248 | 19946718 | Zn(2+)-induced signaling has been shown to be associated with an increase in the tyrosine phosphorylation of insulin receptor (IR), as well as of insulin-like growth factor 1 receptor (IGF-1R) and epidermal growth factor receptor (EGFR) in several cell types. |
| 1249 | 19946718 | Therefore, using a series of pharmacological inhibitors and genetically engineered cells, we have investigated the roles of various R-PTKs in Zn(2+)-induced ERK1/2 and PKB phosphorylation. |
| 1250 | 19946718 | Pretreatment of Chinese hamster ovary (CHO) cells overexpressing a human IR (CHO-HIR cells) with AG1024, an inhibitor for IR protein tyrosine kinase (PTK) and IGF-1R-PTK, blocked Zn(2+)-induced ERK1/2 and PKB phosphorylation, but AG1478, an inhibitor for EGFR, was without effect in CHO cells. |
| 1251 | 19946718 | On the other hand, both of these inhibitors were able to attenuate Zn(2+)-induced phosphorylation of ERK1/2 and PKB in A10 vascular smooth muscle cells. |
| 1252 | 19946718 | Furthermore, both Zn(2+) and insulin-like growth factor 1 failed to stimulate ERK1/2 and PKB phosphorylation in IGF-1R knockout cells. |
| 1253 | 19946718 | Taken together, these data suggest that distinct R-PTKs mediate Zn(2+)-evoked ERK1/2 and PKB phosphorylation in a cell-specific manner. |
| 1254 | 19946718 | Cell-type-specific roles of IGF-1R and EGFR in mediating Zn2+-induced ERK1/2 and PKB phosphorylation. |
| 1255 | 19946718 | Zn(2+) exerts insulin-mimetic and antidiabetic effects in rodent models of insulin resistance, and activates extracellular-signal-regulated kinases 1 and 2 (ERK1/2) and protein kinase B (PKB), key components of the insulin signaling pathway. |
| 1256 | 19946718 | Zn(2+)-induced signaling has been shown to be associated with an increase in the tyrosine phosphorylation of insulin receptor (IR), as well as of insulin-like growth factor 1 receptor (IGF-1R) and epidermal growth factor receptor (EGFR) in several cell types. |
| 1257 | 19946718 | Therefore, using a series of pharmacological inhibitors and genetically engineered cells, we have investigated the roles of various R-PTKs in Zn(2+)-induced ERK1/2 and PKB phosphorylation. |
| 1258 | 19946718 | Pretreatment of Chinese hamster ovary (CHO) cells overexpressing a human IR (CHO-HIR cells) with AG1024, an inhibitor for IR protein tyrosine kinase (PTK) and IGF-1R-PTK, blocked Zn(2+)-induced ERK1/2 and PKB phosphorylation, but AG1478, an inhibitor for EGFR, was without effect in CHO cells. |
| 1259 | 19946718 | On the other hand, both of these inhibitors were able to attenuate Zn(2+)-induced phosphorylation of ERK1/2 and PKB in A10 vascular smooth muscle cells. |
| 1260 | 19946718 | Furthermore, both Zn(2+) and insulin-like growth factor 1 failed to stimulate ERK1/2 and PKB phosphorylation in IGF-1R knockout cells. |
| 1261 | 19946718 | Taken together, these data suggest that distinct R-PTKs mediate Zn(2+)-evoked ERK1/2 and PKB phosphorylation in a cell-specific manner. |
| 1262 | 20029537 | Role of insulin-like growth factor 1 receptor and c-Src in endothelin-1- and angiotensin II-induced PKB phosphorylation, and hypertrophic and proliferative responses in vascular smooth muscle cells. |
| 1263 | 20029537 | Endothelin-1 (ET-1) and angiotensin II (Ang II) are vasoactive peptides believed to contribute to the pathogenesis of vascular abnormalities such as hypertension, atherosclerosis, hypertrophy, and restenosis. |
| 1264 | 20029537 | We have demonstrated that insulin-like growth factor type 1 receptor (IGF-1R) plays a role in transducing the effect of H2O2, leading to protein kinase B (PKB) phosphorylation. |
| 1265 | 20029537 | Since vasoactive peptides elicit their responses through generation of reactive oxygen species, including H2O2, we investigated whether IGF-1R transactivation plays a similar role in ET-1- and Ang II-induced PKB phosphorylation and hypertrophic responses in vascular smooth muscle cells (VSMC). |
| 1266 | 20029537 | AG1024, a specific inhibitor of IGF-1R protein tyrosine kinase (PTK), attenuated both ET-1- and Ang II-induced PKB phosphorylation in a dose-dependent manner. |
| 1267 | 20029537 | ET-1 and Ang II treatment also induced the phosphorylation of tyrosine residues in the autophosphorylation sites of IGF-1R, which were blocked by AG1024. |
| 1268 | 20029537 | In addition, both ET-1 and Ang II evoked tyrosine phosphorylation of c-Src, a nonreceptor PTK, whereas pharmacological inhibition of c-Src PTK activity by PP2, a specific inhibitor of Src-family tyrosine kinase, significantly reduced PKB phosphorylation as well as tyrosine phosphorylation of IGF-1R induced by the 2 vasoactive peptides. |
| 1269 | 20029537 | Furthermore, protein and DNA synthesis enhanced by ET-1 and Ang II were attenuated by AG1024 and PP2. |
| 1270 | 20029537 | In conclusion, these data suggest that IGF-1R PTK and c-Src PTK play a critical role in mediating PKB phosphorylation as well as hypertrophic and proliferative responses induced by ET-1 and Ang II in A10 VSMC. |
| 1271 | 20029537 | Role of insulin-like growth factor 1 receptor and c-Src in endothelin-1- and angiotensin II-induced PKB phosphorylation, and hypertrophic and proliferative responses in vascular smooth muscle cells. |
| 1272 | 20029537 | Endothelin-1 (ET-1) and angiotensin II (Ang II) are vasoactive peptides believed to contribute to the pathogenesis of vascular abnormalities such as hypertension, atherosclerosis, hypertrophy, and restenosis. |
| 1273 | 20029537 | We have demonstrated that insulin-like growth factor type 1 receptor (IGF-1R) plays a role in transducing the effect of H2O2, leading to protein kinase B (PKB) phosphorylation. |
| 1274 | 20029537 | Since vasoactive peptides elicit their responses through generation of reactive oxygen species, including H2O2, we investigated whether IGF-1R transactivation plays a similar role in ET-1- and Ang II-induced PKB phosphorylation and hypertrophic responses in vascular smooth muscle cells (VSMC). |
| 1275 | 20029537 | AG1024, a specific inhibitor of IGF-1R protein tyrosine kinase (PTK), attenuated both ET-1- and Ang II-induced PKB phosphorylation in a dose-dependent manner. |
| 1276 | 20029537 | ET-1 and Ang II treatment also induced the phosphorylation of tyrosine residues in the autophosphorylation sites of IGF-1R, which were blocked by AG1024. |
| 1277 | 20029537 | In addition, both ET-1 and Ang II evoked tyrosine phosphorylation of c-Src, a nonreceptor PTK, whereas pharmacological inhibition of c-Src PTK activity by PP2, a specific inhibitor of Src-family tyrosine kinase, significantly reduced PKB phosphorylation as well as tyrosine phosphorylation of IGF-1R induced by the 2 vasoactive peptides. |
| 1278 | 20029537 | Furthermore, protein and DNA synthesis enhanced by ET-1 and Ang II were attenuated by AG1024 and PP2. |
| 1279 | 20029537 | In conclusion, these data suggest that IGF-1R PTK and c-Src PTK play a critical role in mediating PKB phosphorylation as well as hypertrophic and proliferative responses induced by ET-1 and Ang II in A10 VSMC. |
| 1280 | 20029537 | Role of insulin-like growth factor 1 receptor and c-Src in endothelin-1- and angiotensin II-induced PKB phosphorylation, and hypertrophic and proliferative responses in vascular smooth muscle cells. |
| 1281 | 20029537 | Endothelin-1 (ET-1) and angiotensin II (Ang II) are vasoactive peptides believed to contribute to the pathogenesis of vascular abnormalities such as hypertension, atherosclerosis, hypertrophy, and restenosis. |
| 1282 | 20029537 | We have demonstrated that insulin-like growth factor type 1 receptor (IGF-1R) plays a role in transducing the effect of H2O2, leading to protein kinase B (PKB) phosphorylation. |
| 1283 | 20029537 | Since vasoactive peptides elicit their responses through generation of reactive oxygen species, including H2O2, we investigated whether IGF-1R transactivation plays a similar role in ET-1- and Ang II-induced PKB phosphorylation and hypertrophic responses in vascular smooth muscle cells (VSMC). |
| 1284 | 20029537 | AG1024, a specific inhibitor of IGF-1R protein tyrosine kinase (PTK), attenuated both ET-1- and Ang II-induced PKB phosphorylation in a dose-dependent manner. |
| 1285 | 20029537 | ET-1 and Ang II treatment also induced the phosphorylation of tyrosine residues in the autophosphorylation sites of IGF-1R, which were blocked by AG1024. |
| 1286 | 20029537 | In addition, both ET-1 and Ang II evoked tyrosine phosphorylation of c-Src, a nonreceptor PTK, whereas pharmacological inhibition of c-Src PTK activity by PP2, a specific inhibitor of Src-family tyrosine kinase, significantly reduced PKB phosphorylation as well as tyrosine phosphorylation of IGF-1R induced by the 2 vasoactive peptides. |
| 1287 | 20029537 | Furthermore, protein and DNA synthesis enhanced by ET-1 and Ang II were attenuated by AG1024 and PP2. |
| 1288 | 20029537 | In conclusion, these data suggest that IGF-1R PTK and c-Src PTK play a critical role in mediating PKB phosphorylation as well as hypertrophic and proliferative responses induced by ET-1 and Ang II in A10 VSMC. |
| 1289 | 20029537 | Role of insulin-like growth factor 1 receptor and c-Src in endothelin-1- and angiotensin II-induced PKB phosphorylation, and hypertrophic and proliferative responses in vascular smooth muscle cells. |
| 1290 | 20029537 | Endothelin-1 (ET-1) and angiotensin II (Ang II) are vasoactive peptides believed to contribute to the pathogenesis of vascular abnormalities such as hypertension, atherosclerosis, hypertrophy, and restenosis. |
| 1291 | 20029537 | We have demonstrated that insulin-like growth factor type 1 receptor (IGF-1R) plays a role in transducing the effect of H2O2, leading to protein kinase B (PKB) phosphorylation. |
| 1292 | 20029537 | Since vasoactive peptides elicit their responses through generation of reactive oxygen species, including H2O2, we investigated whether IGF-1R transactivation plays a similar role in ET-1- and Ang II-induced PKB phosphorylation and hypertrophic responses in vascular smooth muscle cells (VSMC). |
| 1293 | 20029537 | AG1024, a specific inhibitor of IGF-1R protein tyrosine kinase (PTK), attenuated both ET-1- and Ang II-induced PKB phosphorylation in a dose-dependent manner. |
| 1294 | 20029537 | ET-1 and Ang II treatment also induced the phosphorylation of tyrosine residues in the autophosphorylation sites of IGF-1R, which were blocked by AG1024. |
| 1295 | 20029537 | In addition, both ET-1 and Ang II evoked tyrosine phosphorylation of c-Src, a nonreceptor PTK, whereas pharmacological inhibition of c-Src PTK activity by PP2, a specific inhibitor of Src-family tyrosine kinase, significantly reduced PKB phosphorylation as well as tyrosine phosphorylation of IGF-1R induced by the 2 vasoactive peptides. |
| 1296 | 20029537 | Furthermore, protein and DNA synthesis enhanced by ET-1 and Ang II were attenuated by AG1024 and PP2. |
| 1297 | 20029537 | In conclusion, these data suggest that IGF-1R PTK and c-Src PTK play a critical role in mediating PKB phosphorylation as well as hypertrophic and proliferative responses induced by ET-1 and Ang II in A10 VSMC. |
| 1298 | 20029537 | Role of insulin-like growth factor 1 receptor and c-Src in endothelin-1- and angiotensin II-induced PKB phosphorylation, and hypertrophic and proliferative responses in vascular smooth muscle cells. |
| 1299 | 20029537 | Endothelin-1 (ET-1) and angiotensin II (Ang II) are vasoactive peptides believed to contribute to the pathogenesis of vascular abnormalities such as hypertension, atherosclerosis, hypertrophy, and restenosis. |
| 1300 | 20029537 | We have demonstrated that insulin-like growth factor type 1 receptor (IGF-1R) plays a role in transducing the effect of H2O2, leading to protein kinase B (PKB) phosphorylation. |
| 1301 | 20029537 | Since vasoactive peptides elicit their responses through generation of reactive oxygen species, including H2O2, we investigated whether IGF-1R transactivation plays a similar role in ET-1- and Ang II-induced PKB phosphorylation and hypertrophic responses in vascular smooth muscle cells (VSMC). |
| 1302 | 20029537 | AG1024, a specific inhibitor of IGF-1R protein tyrosine kinase (PTK), attenuated both ET-1- and Ang II-induced PKB phosphorylation in a dose-dependent manner. |
| 1303 | 20029537 | ET-1 and Ang II treatment also induced the phosphorylation of tyrosine residues in the autophosphorylation sites of IGF-1R, which were blocked by AG1024. |
| 1304 | 20029537 | In addition, both ET-1 and Ang II evoked tyrosine phosphorylation of c-Src, a nonreceptor PTK, whereas pharmacological inhibition of c-Src PTK activity by PP2, a specific inhibitor of Src-family tyrosine kinase, significantly reduced PKB phosphorylation as well as tyrosine phosphorylation of IGF-1R induced by the 2 vasoactive peptides. |
| 1305 | 20029537 | Furthermore, protein and DNA synthesis enhanced by ET-1 and Ang II were attenuated by AG1024 and PP2. |
| 1306 | 20029537 | In conclusion, these data suggest that IGF-1R PTK and c-Src PTK play a critical role in mediating PKB phosphorylation as well as hypertrophic and proliferative responses induced by ET-1 and Ang II in A10 VSMC. |
| 1307 | 20029537 | Role of insulin-like growth factor 1 receptor and c-Src in endothelin-1- and angiotensin II-induced PKB phosphorylation, and hypertrophic and proliferative responses in vascular smooth muscle cells. |
| 1308 | 20029537 | Endothelin-1 (ET-1) and angiotensin II (Ang II) are vasoactive peptides believed to contribute to the pathogenesis of vascular abnormalities such as hypertension, atherosclerosis, hypertrophy, and restenosis. |
| 1309 | 20029537 | We have demonstrated that insulin-like growth factor type 1 receptor (IGF-1R) plays a role in transducing the effect of H2O2, leading to protein kinase B (PKB) phosphorylation. |
| 1310 | 20029537 | Since vasoactive peptides elicit their responses through generation of reactive oxygen species, including H2O2, we investigated whether IGF-1R transactivation plays a similar role in ET-1- and Ang II-induced PKB phosphorylation and hypertrophic responses in vascular smooth muscle cells (VSMC). |
| 1311 | 20029537 | AG1024, a specific inhibitor of IGF-1R protein tyrosine kinase (PTK), attenuated both ET-1- and Ang II-induced PKB phosphorylation in a dose-dependent manner. |
| 1312 | 20029537 | ET-1 and Ang II treatment also induced the phosphorylation of tyrosine residues in the autophosphorylation sites of IGF-1R, which were blocked by AG1024. |
| 1313 | 20029537 | In addition, both ET-1 and Ang II evoked tyrosine phosphorylation of c-Src, a nonreceptor PTK, whereas pharmacological inhibition of c-Src PTK activity by PP2, a specific inhibitor of Src-family tyrosine kinase, significantly reduced PKB phosphorylation as well as tyrosine phosphorylation of IGF-1R induced by the 2 vasoactive peptides. |
| 1314 | 20029537 | Furthermore, protein and DNA synthesis enhanced by ET-1 and Ang II were attenuated by AG1024 and PP2. |
| 1315 | 20029537 | In conclusion, these data suggest that IGF-1R PTK and c-Src PTK play a critical role in mediating PKB phosphorylation as well as hypertrophic and proliferative responses induced by ET-1 and Ang II in A10 VSMC. |
| 1316 | 20029537 | Role of insulin-like growth factor 1 receptor and c-Src in endothelin-1- and angiotensin II-induced PKB phosphorylation, and hypertrophic and proliferative responses in vascular smooth muscle cells. |
| 1317 | 20029537 | Endothelin-1 (ET-1) and angiotensin II (Ang II) are vasoactive peptides believed to contribute to the pathogenesis of vascular abnormalities such as hypertension, atherosclerosis, hypertrophy, and restenosis. |
| 1318 | 20029537 | We have demonstrated that insulin-like growth factor type 1 receptor (IGF-1R) plays a role in transducing the effect of H2O2, leading to protein kinase B (PKB) phosphorylation. |
| 1319 | 20029537 | Since vasoactive peptides elicit their responses through generation of reactive oxygen species, including H2O2, we investigated whether IGF-1R transactivation plays a similar role in ET-1- and Ang II-induced PKB phosphorylation and hypertrophic responses in vascular smooth muscle cells (VSMC). |
| 1320 | 20029537 | AG1024, a specific inhibitor of IGF-1R protein tyrosine kinase (PTK), attenuated both ET-1- and Ang II-induced PKB phosphorylation in a dose-dependent manner. |
| 1321 | 20029537 | ET-1 and Ang II treatment also induced the phosphorylation of tyrosine residues in the autophosphorylation sites of IGF-1R, which were blocked by AG1024. |
| 1322 | 20029537 | In addition, both ET-1 and Ang II evoked tyrosine phosphorylation of c-Src, a nonreceptor PTK, whereas pharmacological inhibition of c-Src PTK activity by PP2, a specific inhibitor of Src-family tyrosine kinase, significantly reduced PKB phosphorylation as well as tyrosine phosphorylation of IGF-1R induced by the 2 vasoactive peptides. |
| 1323 | 20029537 | Furthermore, protein and DNA synthesis enhanced by ET-1 and Ang II were attenuated by AG1024 and PP2. |
| 1324 | 20029537 | In conclusion, these data suggest that IGF-1R PTK and c-Src PTK play a critical role in mediating PKB phosphorylation as well as hypertrophic and proliferative responses induced by ET-1 and Ang II in A10 VSMC. |
| 1325 | 20068149 | MKR mice harbor a transgene encoding a dominant-negative, kinase-dead human insulin-like growth factor-I receptor (IGF-IR) that is expressed exclusively in skeletal muscle, where it acts to inactivate endogenous insulin receptor (IR) and IGF-IR. |
| 1326 | 20068149 | Although lean female MKR mice are insulin resistant and glucose intolerant, displaying accelerated mammary gland development and enhanced phosphorylation of IR/IGF-IR and Akt in mammary tissue, in the context of three different mouse models of breast cancer, these metabolic abnormalities were found to accelerate the development of hyperplastic precancerous lesions. |
| 1327 | 20068149 | Normal or malignant mammary tissue isolated from these mice exhibited increased phosphorylation of IR/IGF-IR and Akt, whereas extracellular signal-regulated kinase 1/2 phosphorylation was largely unaffected. |
| 1328 | 20068149 | MKR mice harbor a transgene encoding a dominant-negative, kinase-dead human insulin-like growth factor-I receptor (IGF-IR) that is expressed exclusively in skeletal muscle, where it acts to inactivate endogenous insulin receptor (IR) and IGF-IR. |
| 1329 | 20068149 | Although lean female MKR mice are insulin resistant and glucose intolerant, displaying accelerated mammary gland development and enhanced phosphorylation of IR/IGF-IR and Akt in mammary tissue, in the context of three different mouse models of breast cancer, these metabolic abnormalities were found to accelerate the development of hyperplastic precancerous lesions. |
| 1330 | 20068149 | Normal or malignant mammary tissue isolated from these mice exhibited increased phosphorylation of IR/IGF-IR and Akt, whereas extracellular signal-regulated kinase 1/2 phosphorylation was largely unaffected. |
| 1331 | 20068149 | MKR mice harbor a transgene encoding a dominant-negative, kinase-dead human insulin-like growth factor-I receptor (IGF-IR) that is expressed exclusively in skeletal muscle, where it acts to inactivate endogenous insulin receptor (IR) and IGF-IR. |
| 1332 | 20068149 | Although lean female MKR mice are insulin resistant and glucose intolerant, displaying accelerated mammary gland development and enhanced phosphorylation of IR/IGF-IR and Akt in mammary tissue, in the context of three different mouse models of breast cancer, these metabolic abnormalities were found to accelerate the development of hyperplastic precancerous lesions. |
| 1333 | 20068149 | Normal or malignant mammary tissue isolated from these mice exhibited increased phosphorylation of IR/IGF-IR and Akt, whereas extracellular signal-regulated kinase 1/2 phosphorylation was largely unaffected. |
| 1334 | 20179633 | Role of genetic variation in insulin-like growth factor 1 receptor on insulin resistance and arterial hypertension. |
| 1335 | 20360006 | Insulin and insulin-like growth factor-1 receptors act as ligand-specific amplitude modulators of a common pathway regulating gene transcription. |
| 1336 | 20360006 | Insulin and insulin-like growth factor-1 (IGF-1) act on highly homologous receptors, yet in vivo elicit distinct effects on metabolism and growth. |
| 1337 | 20360006 | To investigate how the insulin and IGF-1 receptors exert specificity in their biological responses, we assessed their role in the regulation of gene expression using three experimental paradigms: 1) preadipocytes before and after differentiation into adipocytes that express both receptors, but at different ratios; 2) insulin receptor (IR) or IGF1R knock-out preadipocytes that only express the complimentary receptor; and 3) IR/IGF1R double knock-out (DKO) cells reconstituted with the IR, IGF1R, or both. |
| 1338 | 20360006 | In wild-type preadipocytes, which express predominantly IGF1R, microarray analysis revealed approximately 500 IGF-1 regulated genes (p < 0.05). |
| 1339 | 20360006 | After differentiation, when IR levels increase and IGF1R decrease, insulin became the dominant regulator of each of these genes. |
| 1340 | 20360006 | Measurement of the 50 most highly regulated genes by quantitative PCR did not reveal a single gene regulated uniquely via the IR or IGF1R using cells expressing exclusively IGF-1 or insulin receptors. |
| 1341 | 20360006 | Insulin and IGF-1 dose responses from 1 to 100 nm in WT, IRKO, IGFRKO, and DKO cells re-expressing IR, IGF1R, or both showed that insulin and IGF-1 produced effects in proportion to the concentration of ligand and the specific receptor on which they act. |
| 1342 | 20360006 | Thus, IR and IGF1R act as identical portals to the regulation of gene expression, with differences between insulin and IGF-1 effects due to a modulation of the amplitude of the signal created by the specific ligand-receptor interaction. |
| 1343 | 20360006 | Insulin and insulin-like growth factor-1 receptors act as ligand-specific amplitude modulators of a common pathway regulating gene transcription. |
| 1344 | 20360006 | Insulin and insulin-like growth factor-1 (IGF-1) act on highly homologous receptors, yet in vivo elicit distinct effects on metabolism and growth. |
| 1345 | 20360006 | To investigate how the insulin and IGF-1 receptors exert specificity in their biological responses, we assessed their role in the regulation of gene expression using three experimental paradigms: 1) preadipocytes before and after differentiation into adipocytes that express both receptors, but at different ratios; 2) insulin receptor (IR) or IGF1R knock-out preadipocytes that only express the complimentary receptor; and 3) IR/IGF1R double knock-out (DKO) cells reconstituted with the IR, IGF1R, or both. |
| 1346 | 20360006 | In wild-type preadipocytes, which express predominantly IGF1R, microarray analysis revealed approximately 500 IGF-1 regulated genes (p < 0.05). |
| 1347 | 20360006 | After differentiation, when IR levels increase and IGF1R decrease, insulin became the dominant regulator of each of these genes. |
| 1348 | 20360006 | Measurement of the 50 most highly regulated genes by quantitative PCR did not reveal a single gene regulated uniquely via the IR or IGF1R using cells expressing exclusively IGF-1 or insulin receptors. |
| 1349 | 20360006 | Insulin and IGF-1 dose responses from 1 to 100 nm in WT, IRKO, IGFRKO, and DKO cells re-expressing IR, IGF1R, or both showed that insulin and IGF-1 produced effects in proportion to the concentration of ligand and the specific receptor on which they act. |
| 1350 | 20360006 | Thus, IR and IGF1R act as identical portals to the regulation of gene expression, with differences between insulin and IGF-1 effects due to a modulation of the amplitude of the signal created by the specific ligand-receptor interaction. |
| 1351 | 20360006 | Insulin and insulin-like growth factor-1 receptors act as ligand-specific amplitude modulators of a common pathway regulating gene transcription. |
| 1352 | 20360006 | Insulin and insulin-like growth factor-1 (IGF-1) act on highly homologous receptors, yet in vivo elicit distinct effects on metabolism and growth. |
| 1353 | 20360006 | To investigate how the insulin and IGF-1 receptors exert specificity in their biological responses, we assessed their role in the regulation of gene expression using three experimental paradigms: 1) preadipocytes before and after differentiation into adipocytes that express both receptors, but at different ratios; 2) insulin receptor (IR) or IGF1R knock-out preadipocytes that only express the complimentary receptor; and 3) IR/IGF1R double knock-out (DKO) cells reconstituted with the IR, IGF1R, or both. |
| 1354 | 20360006 | In wild-type preadipocytes, which express predominantly IGF1R, microarray analysis revealed approximately 500 IGF-1 regulated genes (p < 0.05). |
| 1355 | 20360006 | After differentiation, when IR levels increase and IGF1R decrease, insulin became the dominant regulator of each of these genes. |
| 1356 | 20360006 | Measurement of the 50 most highly regulated genes by quantitative PCR did not reveal a single gene regulated uniquely via the IR or IGF1R using cells expressing exclusively IGF-1 or insulin receptors. |
| 1357 | 20360006 | Insulin and IGF-1 dose responses from 1 to 100 nm in WT, IRKO, IGFRKO, and DKO cells re-expressing IR, IGF1R, or both showed that insulin and IGF-1 produced effects in proportion to the concentration of ligand and the specific receptor on which they act. |
| 1358 | 20360006 | Thus, IR and IGF1R act as identical portals to the regulation of gene expression, with differences between insulin and IGF-1 effects due to a modulation of the amplitude of the signal created by the specific ligand-receptor interaction. |
| 1359 | 20360006 | Insulin and insulin-like growth factor-1 receptors act as ligand-specific amplitude modulators of a common pathway regulating gene transcription. |
| 1360 | 20360006 | Insulin and insulin-like growth factor-1 (IGF-1) act on highly homologous receptors, yet in vivo elicit distinct effects on metabolism and growth. |
| 1361 | 20360006 | To investigate how the insulin and IGF-1 receptors exert specificity in their biological responses, we assessed their role in the regulation of gene expression using three experimental paradigms: 1) preadipocytes before and after differentiation into adipocytes that express both receptors, but at different ratios; 2) insulin receptor (IR) or IGF1R knock-out preadipocytes that only express the complimentary receptor; and 3) IR/IGF1R double knock-out (DKO) cells reconstituted with the IR, IGF1R, or both. |
| 1362 | 20360006 | In wild-type preadipocytes, which express predominantly IGF1R, microarray analysis revealed approximately 500 IGF-1 regulated genes (p < 0.05). |
| 1363 | 20360006 | After differentiation, when IR levels increase and IGF1R decrease, insulin became the dominant regulator of each of these genes. |
| 1364 | 20360006 | Measurement of the 50 most highly regulated genes by quantitative PCR did not reveal a single gene regulated uniquely via the IR or IGF1R using cells expressing exclusively IGF-1 or insulin receptors. |
| 1365 | 20360006 | Insulin and IGF-1 dose responses from 1 to 100 nm in WT, IRKO, IGFRKO, and DKO cells re-expressing IR, IGF1R, or both showed that insulin and IGF-1 produced effects in proportion to the concentration of ligand and the specific receptor on which they act. |
| 1366 | 20360006 | Thus, IR and IGF1R act as identical portals to the regulation of gene expression, with differences between insulin and IGF-1 effects due to a modulation of the amplitude of the signal created by the specific ligand-receptor interaction. |
| 1367 | 20360006 | Insulin and insulin-like growth factor-1 receptors act as ligand-specific amplitude modulators of a common pathway regulating gene transcription. |
| 1368 | 20360006 | Insulin and insulin-like growth factor-1 (IGF-1) act on highly homologous receptors, yet in vivo elicit distinct effects on metabolism and growth. |
| 1369 | 20360006 | To investigate how the insulin and IGF-1 receptors exert specificity in their biological responses, we assessed their role in the regulation of gene expression using three experimental paradigms: 1) preadipocytes before and after differentiation into adipocytes that express both receptors, but at different ratios; 2) insulin receptor (IR) or IGF1R knock-out preadipocytes that only express the complimentary receptor; and 3) IR/IGF1R double knock-out (DKO) cells reconstituted with the IR, IGF1R, or both. |
| 1370 | 20360006 | In wild-type preadipocytes, which express predominantly IGF1R, microarray analysis revealed approximately 500 IGF-1 regulated genes (p < 0.05). |
| 1371 | 20360006 | After differentiation, when IR levels increase and IGF1R decrease, insulin became the dominant regulator of each of these genes. |
| 1372 | 20360006 | Measurement of the 50 most highly regulated genes by quantitative PCR did not reveal a single gene regulated uniquely via the IR or IGF1R using cells expressing exclusively IGF-1 or insulin receptors. |
| 1373 | 20360006 | Insulin and IGF-1 dose responses from 1 to 100 nm in WT, IRKO, IGFRKO, and DKO cells re-expressing IR, IGF1R, or both showed that insulin and IGF-1 produced effects in proportion to the concentration of ligand and the specific receptor on which they act. |
| 1374 | 20360006 | Thus, IR and IGF1R act as identical portals to the regulation of gene expression, with differences between insulin and IGF-1 effects due to a modulation of the amplitude of the signal created by the specific ligand-receptor interaction. |
| 1375 | 20360006 | Insulin and insulin-like growth factor-1 receptors act as ligand-specific amplitude modulators of a common pathway regulating gene transcription. |
| 1376 | 20360006 | Insulin and insulin-like growth factor-1 (IGF-1) act on highly homologous receptors, yet in vivo elicit distinct effects on metabolism and growth. |
| 1377 | 20360006 | To investigate how the insulin and IGF-1 receptors exert specificity in their biological responses, we assessed their role in the regulation of gene expression using three experimental paradigms: 1) preadipocytes before and after differentiation into adipocytes that express both receptors, but at different ratios; 2) insulin receptor (IR) or IGF1R knock-out preadipocytes that only express the complimentary receptor; and 3) IR/IGF1R double knock-out (DKO) cells reconstituted with the IR, IGF1R, or both. |
| 1378 | 20360006 | In wild-type preadipocytes, which express predominantly IGF1R, microarray analysis revealed approximately 500 IGF-1 regulated genes (p < 0.05). |
| 1379 | 20360006 | After differentiation, when IR levels increase and IGF1R decrease, insulin became the dominant regulator of each of these genes. |
| 1380 | 20360006 | Measurement of the 50 most highly regulated genes by quantitative PCR did not reveal a single gene regulated uniquely via the IR or IGF1R using cells expressing exclusively IGF-1 or insulin receptors. |
| 1381 | 20360006 | Insulin and IGF-1 dose responses from 1 to 100 nm in WT, IRKO, IGFRKO, and DKO cells re-expressing IR, IGF1R, or both showed that insulin and IGF-1 produced effects in proportion to the concentration of ligand and the specific receptor on which they act. |
| 1382 | 20360006 | Thus, IR and IGF1R act as identical portals to the regulation of gene expression, with differences between insulin and IGF-1 effects due to a modulation of the amplitude of the signal created by the specific ligand-receptor interaction. |
| 1383 | 20392809 | Insulin-like growth factor-I regulation of immune function: a potential therapeutic target in autoimmune diseases? |
| 1384 | 20392809 | This topically limited review explores the relationship between the immune system and insulin-like growth factors (IGF-I and IGF-II) and the proteins through which they act, including IGF-I receptor (IGF-IR) and the IGF-I binding proteins. |
| 1385 | 20392809 | Many of the consequences ascribed to IGF-IR activation result from its association with several accessory proteins that are either identical or closely related to those involved in insulin receptor signaling. |
| 1386 | 20392809 | Relatively recent awareness that IGF-I and IGF-IR regulate immune function has cast this pathway in an unexpected light; it may represent an important switch governing the quality and amplitude of immune responses. |
| 1387 | 20392809 | IGF-I/IGF-IR signaling may also participate in the pathogenesis of autoimmune diseases, although its relationship with these processes seems complex and relatively unexplored. |
| 1388 | 20392809 | On the one hand, IGF-I seems to protect experimental animals from developing insulin-deficient diabetes mellitus. |
| 1389 | 20392809 | Potential involvement of IGF-I and IGF-IR in the pathogenesis of autoimmune diseases suggests that this pathway might constitute an attractive therapeutic target. |
| 1390 | 20392809 | Insulin-like growth factor-I regulation of immune function: a potential therapeutic target in autoimmune diseases? |
| 1391 | 20392809 | This topically limited review explores the relationship between the immune system and insulin-like growth factors (IGF-I and IGF-II) and the proteins through which they act, including IGF-I receptor (IGF-IR) and the IGF-I binding proteins. |
| 1392 | 20392809 | Many of the consequences ascribed to IGF-IR activation result from its association with several accessory proteins that are either identical or closely related to those involved in insulin receptor signaling. |
| 1393 | 20392809 | Relatively recent awareness that IGF-I and IGF-IR regulate immune function has cast this pathway in an unexpected light; it may represent an important switch governing the quality and amplitude of immune responses. |
| 1394 | 20392809 | IGF-I/IGF-IR signaling may also participate in the pathogenesis of autoimmune diseases, although its relationship with these processes seems complex and relatively unexplored. |
| 1395 | 20392809 | On the one hand, IGF-I seems to protect experimental animals from developing insulin-deficient diabetes mellitus. |
| 1396 | 20392809 | Potential involvement of IGF-I and IGF-IR in the pathogenesis of autoimmune diseases suggests that this pathway might constitute an attractive therapeutic target. |
| 1397 | 20392809 | Insulin-like growth factor-I regulation of immune function: a potential therapeutic target in autoimmune diseases? |
| 1398 | 20392809 | This topically limited review explores the relationship between the immune system and insulin-like growth factors (IGF-I and IGF-II) and the proteins through which they act, including IGF-I receptor (IGF-IR) and the IGF-I binding proteins. |
| 1399 | 20392809 | Many of the consequences ascribed to IGF-IR activation result from its association with several accessory proteins that are either identical or closely related to those involved in insulin receptor signaling. |
| 1400 | 20392809 | Relatively recent awareness that IGF-I and IGF-IR regulate immune function has cast this pathway in an unexpected light; it may represent an important switch governing the quality and amplitude of immune responses. |
| 1401 | 20392809 | IGF-I/IGF-IR signaling may also participate in the pathogenesis of autoimmune diseases, although its relationship with these processes seems complex and relatively unexplored. |
| 1402 | 20392809 | On the one hand, IGF-I seems to protect experimental animals from developing insulin-deficient diabetes mellitus. |
| 1403 | 20392809 | Potential involvement of IGF-I and IGF-IR in the pathogenesis of autoimmune diseases suggests that this pathway might constitute an attractive therapeutic target. |
| 1404 | 20392809 | Insulin-like growth factor-I regulation of immune function: a potential therapeutic target in autoimmune diseases? |
| 1405 | 20392809 | This topically limited review explores the relationship between the immune system and insulin-like growth factors (IGF-I and IGF-II) and the proteins through which they act, including IGF-I receptor (IGF-IR) and the IGF-I binding proteins. |
| 1406 | 20392809 | Many of the consequences ascribed to IGF-IR activation result from its association with several accessory proteins that are either identical or closely related to those involved in insulin receptor signaling. |
| 1407 | 20392809 | Relatively recent awareness that IGF-I and IGF-IR regulate immune function has cast this pathway in an unexpected light; it may represent an important switch governing the quality and amplitude of immune responses. |
| 1408 | 20392809 | IGF-I/IGF-IR signaling may also participate in the pathogenesis of autoimmune diseases, although its relationship with these processes seems complex and relatively unexplored. |
| 1409 | 20392809 | On the one hand, IGF-I seems to protect experimental animals from developing insulin-deficient diabetes mellitus. |
| 1410 | 20392809 | Potential involvement of IGF-I and IGF-IR in the pathogenesis of autoimmune diseases suggests that this pathway might constitute an attractive therapeutic target. |
| 1411 | 20392809 | Insulin-like growth factor-I regulation of immune function: a potential therapeutic target in autoimmune diseases? |
| 1412 | 20392809 | This topically limited review explores the relationship between the immune system and insulin-like growth factors (IGF-I and IGF-II) and the proteins through which they act, including IGF-I receptor (IGF-IR) and the IGF-I binding proteins. |
| 1413 | 20392809 | Many of the consequences ascribed to IGF-IR activation result from its association with several accessory proteins that are either identical or closely related to those involved in insulin receptor signaling. |
| 1414 | 20392809 | Relatively recent awareness that IGF-I and IGF-IR regulate immune function has cast this pathway in an unexpected light; it may represent an important switch governing the quality and amplitude of immune responses. |
| 1415 | 20392809 | IGF-I/IGF-IR signaling may also participate in the pathogenesis of autoimmune diseases, although its relationship with these processes seems complex and relatively unexplored. |
| 1416 | 20392809 | On the one hand, IGF-I seems to protect experimental animals from developing insulin-deficient diabetes mellitus. |
| 1417 | 20392809 | Potential involvement of IGF-I and IGF-IR in the pathogenesis of autoimmune diseases suggests that this pathway might constitute an attractive therapeutic target. |
| 1418 | 20457905 | Insulin receptor functionally enhances multistage tumor progression and conveys intrinsic resistance to IGF-1R targeted therapy. |
| 1419 | 20457905 | The type 1 insulin-like growth factor receptor (IGF-1R) tyrosine kinase is an important mediator of the protumorigenic effects of IGF-I/II, and inhibitors of IGF-1R signaling are currently being tested in clinical cancer trials aiming to assess the utility of this receptor as a therapeutic target. |
| 1420 | 20457905 | Despite mounting evidence that the highly homologous insulin receptor (IR) can also convey protumorigenic signals, its direct role in cancer progression has not been genetically defined in vivo, and it remains unclear whether such a role for IR signaling could compromise the efficacy of selective IGF-1R targeting strategies. |
| 1421 | 20457905 | A transgenic mouse model of pancreatic neuroendocrine carcinogenesis engages the IGF signaling pathway, as revealed by its dependence on IGF-II and by accelerated malignant progression upon IGF-1R overexpression. |
| 1422 | 20457905 | Insulin receptor functionally enhances multistage tumor progression and conveys intrinsic resistance to IGF-1R targeted therapy. |
| 1423 | 20457905 | The type 1 insulin-like growth factor receptor (IGF-1R) tyrosine kinase is an important mediator of the protumorigenic effects of IGF-I/II, and inhibitors of IGF-1R signaling are currently being tested in clinical cancer trials aiming to assess the utility of this receptor as a therapeutic target. |
| 1424 | 20457905 | Despite mounting evidence that the highly homologous insulin receptor (IR) can also convey protumorigenic signals, its direct role in cancer progression has not been genetically defined in vivo, and it remains unclear whether such a role for IR signaling could compromise the efficacy of selective IGF-1R targeting strategies. |
| 1425 | 20457905 | A transgenic mouse model of pancreatic neuroendocrine carcinogenesis engages the IGF signaling pathway, as revealed by its dependence on IGF-II and by accelerated malignant progression upon IGF-1R overexpression. |
| 1426 | 20457905 | Insulin receptor functionally enhances multistage tumor progression and conveys intrinsic resistance to IGF-1R targeted therapy. |
| 1427 | 20457905 | The type 1 insulin-like growth factor receptor (IGF-1R) tyrosine kinase is an important mediator of the protumorigenic effects of IGF-I/II, and inhibitors of IGF-1R signaling are currently being tested in clinical cancer trials aiming to assess the utility of this receptor as a therapeutic target. |
| 1428 | 20457905 | Despite mounting evidence that the highly homologous insulin receptor (IR) can also convey protumorigenic signals, its direct role in cancer progression has not been genetically defined in vivo, and it remains unclear whether such a role for IR signaling could compromise the efficacy of selective IGF-1R targeting strategies. |
| 1429 | 20457905 | A transgenic mouse model of pancreatic neuroendocrine carcinogenesis engages the IGF signaling pathway, as revealed by its dependence on IGF-II and by accelerated malignant progression upon IGF-1R overexpression. |
| 1430 | 20457905 | Insulin receptor functionally enhances multistage tumor progression and conveys intrinsic resistance to IGF-1R targeted therapy. |
| 1431 | 20457905 | The type 1 insulin-like growth factor receptor (IGF-1R) tyrosine kinase is an important mediator of the protumorigenic effects of IGF-I/II, and inhibitors of IGF-1R signaling are currently being tested in clinical cancer trials aiming to assess the utility of this receptor as a therapeutic target. |
| 1432 | 20457905 | Despite mounting evidence that the highly homologous insulin receptor (IR) can also convey protumorigenic signals, its direct role in cancer progression has not been genetically defined in vivo, and it remains unclear whether such a role for IR signaling could compromise the efficacy of selective IGF-1R targeting strategies. |
| 1433 | 20457905 | A transgenic mouse model of pancreatic neuroendocrine carcinogenesis engages the IGF signaling pathway, as revealed by its dependence on IGF-II and by accelerated malignant progression upon IGF-1R overexpression. |
| 1434 | 20506299 | PTP1B deficiency enhances liver growth during suckling by increasing the expression of insulin-like growth factor-I. |
| 1435 | 20506299 | Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of insulin and tyrosine kinase growth factor signaling. |
| 1436 | 20506299 | We have recently demonstrated that PTP1B deficiency increases GLUT2/insulin receptor (IR) A complexes and glucose uptake in suckling, but not adult, primary hepatocytes. |
| 1437 | 20506299 | Conversely, the activity of glucose 6-phosphate dehydrogenase (G6PD), the rate limiting enzyme of the pentose phosphate cycle (PPC) which provides substrates for DNA synthesis, was enhanced in the liver of PTP1B(-/-) animals. |
| 1438 | 20506299 | At the molecular level, STAT 5B phosphorylation, IGF-I mRNA, and protein levels as well as IGF-IR tyrosine phosphorylation were increased in the livers of PTP1B-deficient neonates. |
| 1439 | 20506299 | The effects of PTP1B deficiency on G6PD activity, STAT 5B/IGF-I/IGF-IR axis, PCNA expression and liver growth during suckling were maintained by transferring PTP1B(-/-) embryos (PTP1B(-/-T)) to a wild-type female. |
| 1440 | 20506299 | PTP1B deficiency enhances liver growth during suckling by increasing the expression of insulin-like growth factor-I. |
| 1441 | 20506299 | Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of insulin and tyrosine kinase growth factor signaling. |
| 1442 | 20506299 | We have recently demonstrated that PTP1B deficiency increases GLUT2/insulin receptor (IR) A complexes and glucose uptake in suckling, but not adult, primary hepatocytes. |
| 1443 | 20506299 | Conversely, the activity of glucose 6-phosphate dehydrogenase (G6PD), the rate limiting enzyme of the pentose phosphate cycle (PPC) which provides substrates for DNA synthesis, was enhanced in the liver of PTP1B(-/-) animals. |
| 1444 | 20506299 | At the molecular level, STAT 5B phosphorylation, IGF-I mRNA, and protein levels as well as IGF-IR tyrosine phosphorylation were increased in the livers of PTP1B-deficient neonates. |
| 1445 | 20506299 | The effects of PTP1B deficiency on G6PD activity, STAT 5B/IGF-I/IGF-IR axis, PCNA expression and liver growth during suckling were maintained by transferring PTP1B(-/-) embryos (PTP1B(-/-T)) to a wild-type female. |
| 1446 | 20554184 | Quantitative real-time PCR was used to investigate CE effects on the expression of genes coding for adipokines, glucose transporter (GLUT) family, and insulin-signaling components in mouse 3T3-L1 adipocytes. |
| 1447 | 20554184 | CE decreased the expression of further genes encoding insulin-signaling pathway proteins including GSK3B, IGF1R, IGF2R, and PIK3R1. |
| 1448 | 20555420 | Involvement of insulin-like growth factor 1 receptor transactivation in endothelin-1-induced signaling in vascular smooth muscle cells. |
| 1449 | 20555420 | However, recent studies have implicated insulin-like growth factor 1 receptor transactivation in this process. |
| 1450 | 20555420 | In this review, we will examine the contribution of both insulin-like growth factor 1 receptor and c-Src in mediating ET-1-induced signaling responses in vascular smooth muscle cells. |
| 1451 | 20555420 | Involvement of insulin-like growth factor 1 receptor transactivation in endothelin-1-induced signaling in vascular smooth muscle cells. |
| 1452 | 20555420 | However, recent studies have implicated insulin-like growth factor 1 receptor transactivation in this process. |
| 1453 | 20555420 | In this review, we will examine the contribution of both insulin-like growth factor 1 receptor and c-Src in mediating ET-1-induced signaling responses in vascular smooth muscle cells. |
| 1454 | 20555420 | Involvement of insulin-like growth factor 1 receptor transactivation in endothelin-1-induced signaling in vascular smooth muscle cells. |
| 1455 | 20555420 | However, recent studies have implicated insulin-like growth factor 1 receptor transactivation in this process. |
| 1456 | 20555420 | In this review, we will examine the contribution of both insulin-like growth factor 1 receptor and c-Src in mediating ET-1-induced signaling responses in vascular smooth muscle cells. |
| 1457 | 20555424 | Regulation of IRS-2 signaling by IGF-1 receptor in the diabetic rat heart. |
| 1458 | 20555424 | Since insulin/insulin-like growth factor 1 receptor (IGF-1R) can activate vascular endothelial growth factor to promote vascular growth, reduced IGF-1R signaling in the type I diabetic heart could be detrimental, leading to reduced, collateral blood vessel growth. |
| 1459 | 20555424 | Diabetes increased TNF-alpha, interleukin-6 (IL-6), and IL-1alpha levels in the heart. |
| 1460 | 20555424 | JNK and p42/p44 activity was significantly increased in the diabetic heart, while IGF-1R phosphorylation, IRS-2 tyrosine phosphorylation, and Akt activities were reduced. |
| 1461 | 20555424 | These results suggest that diabetes activates multiple inflammatory markers in the heart, which then signal a decrease in the activities of key players in the insulin-signaling cascade, namely IGF-1R, IRS-2, and Akt, to regulate apoptosis. |
| 1462 | 20555424 | Regulation of IRS-2 signaling by IGF-1 receptor in the diabetic rat heart. |
| 1463 | 20555424 | Since insulin/insulin-like growth factor 1 receptor (IGF-1R) can activate vascular endothelial growth factor to promote vascular growth, reduced IGF-1R signaling in the type I diabetic heart could be detrimental, leading to reduced, collateral blood vessel growth. |
| 1464 | 20555424 | Diabetes increased TNF-alpha, interleukin-6 (IL-6), and IL-1alpha levels in the heart. |
| 1465 | 20555424 | JNK and p42/p44 activity was significantly increased in the diabetic heart, while IGF-1R phosphorylation, IRS-2 tyrosine phosphorylation, and Akt activities were reduced. |
| 1466 | 20555424 | These results suggest that diabetes activates multiple inflammatory markers in the heart, which then signal a decrease in the activities of key players in the insulin-signaling cascade, namely IGF-1R, IRS-2, and Akt, to regulate apoptosis. |
| 1467 | 20555424 | Regulation of IRS-2 signaling by IGF-1 receptor in the diabetic rat heart. |
| 1468 | 20555424 | Since insulin/insulin-like growth factor 1 receptor (IGF-1R) can activate vascular endothelial growth factor to promote vascular growth, reduced IGF-1R signaling in the type I diabetic heart could be detrimental, leading to reduced, collateral blood vessel growth. |
| 1469 | 20555424 | Diabetes increased TNF-alpha, interleukin-6 (IL-6), and IL-1alpha levels in the heart. |
| 1470 | 20555424 | JNK and p42/p44 activity was significantly increased in the diabetic heart, while IGF-1R phosphorylation, IRS-2 tyrosine phosphorylation, and Akt activities were reduced. |
| 1471 | 20555424 | These results suggest that diabetes activates multiple inflammatory markers in the heart, which then signal a decrease in the activities of key players in the insulin-signaling cascade, namely IGF-1R, IRS-2, and Akt, to regulate apoptosis. |
| 1472 | 20621572 | The mechanism of increased tumor activity of insulin analogues is explained by the fact that they act through insulin receptors (IR) and insulin-like growth factor-1 (IGF-1R), stimulating cell growth and inhibiting apoptosis. |
| 1473 | 20621572 | There are two major mechanisms: an increase in the binding time of insulin to IR and increased activation of IGF-1R. |
| 1474 | 20621572 | Therefore, to evaluate the safety of an analogue, the slower dissociation rate from its insulin receptor must be excluded, as well as the increased affinity for the IGF-1 receptor. |
| 1475 | 20621572 | The mechanism of increased tumor activity of insulin analogues is explained by the fact that they act through insulin receptors (IR) and insulin-like growth factor-1 (IGF-1R), stimulating cell growth and inhibiting apoptosis. |
| 1476 | 20621572 | There are two major mechanisms: an increase in the binding time of insulin to IR and increased activation of IGF-1R. |
| 1477 | 20621572 | Therefore, to evaluate the safety of an analogue, the slower dissociation rate from its insulin receptor must be excluded, as well as the increased affinity for the IGF-1 receptor. |
| 1478 | 20633551 | High levels of glucose induce apoptosis in cardiomyocyte via epigenetic regulation of the insulin-like growth factor receptor. |
| 1479 | 20633551 | We investigate whether HG-induced repression of insulin-like growth factor 1 receptor (IGF-1R) mediated by epigenetic modifications is one potential mechanism. |
| 1480 | 20633551 | We found that HG resulted in decreased IGF-1 receptor (IGF-1R) mRNA levels, and IGF-1R protein when compared with H9C2 rat cardiomyocyte cells incubated in normal glucose. |
| 1481 | 20633551 | The effects of HG on reduced expression of IGF-1R and increased apoptosis were blocked by silencing p53 with small interference RNA but not by non-targeting scrambled siRNA. |
| 1482 | 20633551 | Moreover, HG negatively regulated IGF-1R promoter activity as determined by ChIP analysis, which was dependent on p53 since siRNA-p53 attenuated the effects of HG on IGF-1R promoter activity. |
| 1483 | 20633551 | HG also increased the association of p53 with histone deacetylase 1 (HDAC1), and decreased the association of acetylated histone-4 with the IGF-1R promoter. |
| 1484 | 20633551 | Furthermore, HDAC inhibitor relieved the repression of IGF-1R following HG state. |
| 1485 | 20633551 | These results suggest that HG-induced repression of IGF-1R is mediated by the association of p53 with the IGF-1R promoter, and by the subsequent enhanced recruitment of chromatin-modifying proteins, such as HDAC1, to the IGF-1R promoter-p53 complex. |
| 1486 | 20633551 | In conclusion, our data demonstrate that HG decreases expression of IGF-1R and decreases the association of acetylated histone-4 with the IGF-1R promoter. |
| 1487 | 20633551 | High levels of glucose induce apoptosis in cardiomyocyte via epigenetic regulation of the insulin-like growth factor receptor. |
| 1488 | 20633551 | We investigate whether HG-induced repression of insulin-like growth factor 1 receptor (IGF-1R) mediated by epigenetic modifications is one potential mechanism. |
| 1489 | 20633551 | We found that HG resulted in decreased IGF-1 receptor (IGF-1R) mRNA levels, and IGF-1R protein when compared with H9C2 rat cardiomyocyte cells incubated in normal glucose. |
| 1490 | 20633551 | The effects of HG on reduced expression of IGF-1R and increased apoptosis were blocked by silencing p53 with small interference RNA but not by non-targeting scrambled siRNA. |
| 1491 | 20633551 | Moreover, HG negatively regulated IGF-1R promoter activity as determined by ChIP analysis, which was dependent on p53 since siRNA-p53 attenuated the effects of HG on IGF-1R promoter activity. |
| 1492 | 20633551 | HG also increased the association of p53 with histone deacetylase 1 (HDAC1), and decreased the association of acetylated histone-4 with the IGF-1R promoter. |
| 1493 | 20633551 | Furthermore, HDAC inhibitor relieved the repression of IGF-1R following HG state. |
| 1494 | 20633551 | These results suggest that HG-induced repression of IGF-1R is mediated by the association of p53 with the IGF-1R promoter, and by the subsequent enhanced recruitment of chromatin-modifying proteins, such as HDAC1, to the IGF-1R promoter-p53 complex. |
| 1495 | 20633551 | In conclusion, our data demonstrate that HG decreases expression of IGF-1R and decreases the association of acetylated histone-4 with the IGF-1R promoter. |
| 1496 | 20633551 | High levels of glucose induce apoptosis in cardiomyocyte via epigenetic regulation of the insulin-like growth factor receptor. |
| 1497 | 20633551 | We investigate whether HG-induced repression of insulin-like growth factor 1 receptor (IGF-1R) mediated by epigenetic modifications is one potential mechanism. |
| 1498 | 20633551 | We found that HG resulted in decreased IGF-1 receptor (IGF-1R) mRNA levels, and IGF-1R protein when compared with H9C2 rat cardiomyocyte cells incubated in normal glucose. |
| 1499 | 20633551 | The effects of HG on reduced expression of IGF-1R and increased apoptosis were blocked by silencing p53 with small interference RNA but not by non-targeting scrambled siRNA. |
| 1500 | 20633551 | Moreover, HG negatively regulated IGF-1R promoter activity as determined by ChIP analysis, which was dependent on p53 since siRNA-p53 attenuated the effects of HG on IGF-1R promoter activity. |
| 1501 | 20633551 | HG also increased the association of p53 with histone deacetylase 1 (HDAC1), and decreased the association of acetylated histone-4 with the IGF-1R promoter. |
| 1502 | 20633551 | Furthermore, HDAC inhibitor relieved the repression of IGF-1R following HG state. |
| 1503 | 20633551 | These results suggest that HG-induced repression of IGF-1R is mediated by the association of p53 with the IGF-1R promoter, and by the subsequent enhanced recruitment of chromatin-modifying proteins, such as HDAC1, to the IGF-1R promoter-p53 complex. |
| 1504 | 20633551 | In conclusion, our data demonstrate that HG decreases expression of IGF-1R and decreases the association of acetylated histone-4 with the IGF-1R promoter. |
| 1505 | 20633551 | High levels of glucose induce apoptosis in cardiomyocyte via epigenetic regulation of the insulin-like growth factor receptor. |
| 1506 | 20633551 | We investigate whether HG-induced repression of insulin-like growth factor 1 receptor (IGF-1R) mediated by epigenetic modifications is one potential mechanism. |
| 1507 | 20633551 | We found that HG resulted in decreased IGF-1 receptor (IGF-1R) mRNA levels, and IGF-1R protein when compared with H9C2 rat cardiomyocyte cells incubated in normal glucose. |
| 1508 | 20633551 | The effects of HG on reduced expression of IGF-1R and increased apoptosis were blocked by silencing p53 with small interference RNA but not by non-targeting scrambled siRNA. |
| 1509 | 20633551 | Moreover, HG negatively regulated IGF-1R promoter activity as determined by ChIP analysis, which was dependent on p53 since siRNA-p53 attenuated the effects of HG on IGF-1R promoter activity. |
| 1510 | 20633551 | HG also increased the association of p53 with histone deacetylase 1 (HDAC1), and decreased the association of acetylated histone-4 with the IGF-1R promoter. |
| 1511 | 20633551 | Furthermore, HDAC inhibitor relieved the repression of IGF-1R following HG state. |
| 1512 | 20633551 | These results suggest that HG-induced repression of IGF-1R is mediated by the association of p53 with the IGF-1R promoter, and by the subsequent enhanced recruitment of chromatin-modifying proteins, such as HDAC1, to the IGF-1R promoter-p53 complex. |
| 1513 | 20633551 | In conclusion, our data demonstrate that HG decreases expression of IGF-1R and decreases the association of acetylated histone-4 with the IGF-1R promoter. |
| 1514 | 20633551 | High levels of glucose induce apoptosis in cardiomyocyte via epigenetic regulation of the insulin-like growth factor receptor. |
| 1515 | 20633551 | We investigate whether HG-induced repression of insulin-like growth factor 1 receptor (IGF-1R) mediated by epigenetic modifications is one potential mechanism. |
| 1516 | 20633551 | We found that HG resulted in decreased IGF-1 receptor (IGF-1R) mRNA levels, and IGF-1R protein when compared with H9C2 rat cardiomyocyte cells incubated in normal glucose. |
| 1517 | 20633551 | The effects of HG on reduced expression of IGF-1R and increased apoptosis were blocked by silencing p53 with small interference RNA but not by non-targeting scrambled siRNA. |
| 1518 | 20633551 | Moreover, HG negatively regulated IGF-1R promoter activity as determined by ChIP analysis, which was dependent on p53 since siRNA-p53 attenuated the effects of HG on IGF-1R promoter activity. |
| 1519 | 20633551 | HG also increased the association of p53 with histone deacetylase 1 (HDAC1), and decreased the association of acetylated histone-4 with the IGF-1R promoter. |
| 1520 | 20633551 | Furthermore, HDAC inhibitor relieved the repression of IGF-1R following HG state. |
| 1521 | 20633551 | These results suggest that HG-induced repression of IGF-1R is mediated by the association of p53 with the IGF-1R promoter, and by the subsequent enhanced recruitment of chromatin-modifying proteins, such as HDAC1, to the IGF-1R promoter-p53 complex. |
| 1522 | 20633551 | In conclusion, our data demonstrate that HG decreases expression of IGF-1R and decreases the association of acetylated histone-4 with the IGF-1R promoter. |
| 1523 | 20633551 | High levels of glucose induce apoptosis in cardiomyocyte via epigenetic regulation of the insulin-like growth factor receptor. |
| 1524 | 20633551 | We investigate whether HG-induced repression of insulin-like growth factor 1 receptor (IGF-1R) mediated by epigenetic modifications is one potential mechanism. |
| 1525 | 20633551 | We found that HG resulted in decreased IGF-1 receptor (IGF-1R) mRNA levels, and IGF-1R protein when compared with H9C2 rat cardiomyocyte cells incubated in normal glucose. |
| 1526 | 20633551 | The effects of HG on reduced expression of IGF-1R and increased apoptosis were blocked by silencing p53 with small interference RNA but not by non-targeting scrambled siRNA. |
| 1527 | 20633551 | Moreover, HG negatively regulated IGF-1R promoter activity as determined by ChIP analysis, which was dependent on p53 since siRNA-p53 attenuated the effects of HG on IGF-1R promoter activity. |
| 1528 | 20633551 | HG also increased the association of p53 with histone deacetylase 1 (HDAC1), and decreased the association of acetylated histone-4 with the IGF-1R promoter. |
| 1529 | 20633551 | Furthermore, HDAC inhibitor relieved the repression of IGF-1R following HG state. |
| 1530 | 20633551 | These results suggest that HG-induced repression of IGF-1R is mediated by the association of p53 with the IGF-1R promoter, and by the subsequent enhanced recruitment of chromatin-modifying proteins, such as HDAC1, to the IGF-1R promoter-p53 complex. |
| 1531 | 20633551 | In conclusion, our data demonstrate that HG decreases expression of IGF-1R and decreases the association of acetylated histone-4 with the IGF-1R promoter. |
| 1532 | 20633551 | High levels of glucose induce apoptosis in cardiomyocyte via epigenetic regulation of the insulin-like growth factor receptor. |
| 1533 | 20633551 | We investigate whether HG-induced repression of insulin-like growth factor 1 receptor (IGF-1R) mediated by epigenetic modifications is one potential mechanism. |
| 1534 | 20633551 | We found that HG resulted in decreased IGF-1 receptor (IGF-1R) mRNA levels, and IGF-1R protein when compared with H9C2 rat cardiomyocyte cells incubated in normal glucose. |
| 1535 | 20633551 | The effects of HG on reduced expression of IGF-1R and increased apoptosis were blocked by silencing p53 with small interference RNA but not by non-targeting scrambled siRNA. |
| 1536 | 20633551 | Moreover, HG negatively regulated IGF-1R promoter activity as determined by ChIP analysis, which was dependent on p53 since siRNA-p53 attenuated the effects of HG on IGF-1R promoter activity. |
| 1537 | 20633551 | HG also increased the association of p53 with histone deacetylase 1 (HDAC1), and decreased the association of acetylated histone-4 with the IGF-1R promoter. |
| 1538 | 20633551 | Furthermore, HDAC inhibitor relieved the repression of IGF-1R following HG state. |
| 1539 | 20633551 | These results suggest that HG-induced repression of IGF-1R is mediated by the association of p53 with the IGF-1R promoter, and by the subsequent enhanced recruitment of chromatin-modifying proteins, such as HDAC1, to the IGF-1R promoter-p53 complex. |
| 1540 | 20633551 | In conclusion, our data demonstrate that HG decreases expression of IGF-1R and decreases the association of acetylated histone-4 with the IGF-1R promoter. |
| 1541 | 20633551 | High levels of glucose induce apoptosis in cardiomyocyte via epigenetic regulation of the insulin-like growth factor receptor. |
| 1542 | 20633551 | We investigate whether HG-induced repression of insulin-like growth factor 1 receptor (IGF-1R) mediated by epigenetic modifications is one potential mechanism. |
| 1543 | 20633551 | We found that HG resulted in decreased IGF-1 receptor (IGF-1R) mRNA levels, and IGF-1R protein when compared with H9C2 rat cardiomyocyte cells incubated in normal glucose. |
| 1544 | 20633551 | The effects of HG on reduced expression of IGF-1R and increased apoptosis were blocked by silencing p53 with small interference RNA but not by non-targeting scrambled siRNA. |
| 1545 | 20633551 | Moreover, HG negatively regulated IGF-1R promoter activity as determined by ChIP analysis, which was dependent on p53 since siRNA-p53 attenuated the effects of HG on IGF-1R promoter activity. |
| 1546 | 20633551 | HG also increased the association of p53 with histone deacetylase 1 (HDAC1), and decreased the association of acetylated histone-4 with the IGF-1R promoter. |
| 1547 | 20633551 | Furthermore, HDAC inhibitor relieved the repression of IGF-1R following HG state. |
| 1548 | 20633551 | These results suggest that HG-induced repression of IGF-1R is mediated by the association of p53 with the IGF-1R promoter, and by the subsequent enhanced recruitment of chromatin-modifying proteins, such as HDAC1, to the IGF-1R promoter-p53 complex. |
| 1549 | 20633551 | In conclusion, our data demonstrate that HG decreases expression of IGF-1R and decreases the association of acetylated histone-4 with the IGF-1R promoter. |
| 1550 | 20663687 | The proliferating role of insulin and insulin-like growth factors in cancer. |
| 1551 | 20663687 | Hyperinsulinemia leads to increased expression of insulin-like growth factor (IGF)-I expression. |
| 1552 | 20663687 | In fact, increased insulin, IGF-I and IGF-II levels are associated with tumor growth in vitro, in animal models, and in epidemiological studies in humans. |
| 1553 | 20663687 | In this paper, we discuss the roles of insulin, IGF-I and IGF-II, their interaction with the insulin receptor (IR) and IGF-I receptor (IGF-IR), and their signaling pathways and regulation as these pertain to tumor growth. |
| 1554 | 20810672 | In lung tissue, metformin did not activate AMPK but inhibited phosphorylation of insulin-like growth factor-I receptor/insulin receptor (IGF-1R/IR), Akt, extracellular signal-regulated kinase (ERK), and mTOR. |
| 1555 | 20810672 | This suggested that metformin indirectly inhibited mTOR in lung tissue by decreasing activation of insulin-like growth factor-I receptor/insulin receptor and Akt upstream of mTOR. |
| 1556 | 20947509 | Genetic analysis of type-1 insulin-like growth factor receptor signaling through insulin receptor substrate-1 and -2 in pancreatic beta cells. |
| 1557 | 20947509 | Inactivation of insulin receptor (InsR), IGF1 receptor (Igf1r), or Irs1 in β cells impairs insulin secretion. |
| 1558 | 20947509 | To examine genetically the involvement of Irs1 and Irs2 in Igf1r signaling, we generated double mutant mice lacking Igf1r specifically in pancreatic β cells in an Irs1- or Irs2-null background. |
| 1559 | 20947509 | We show that Igf1r/Irs1 double mutants do not differ phenotypically from Irs1 single mutants and exhibit hyperinsulinemia, while maintaining normal β cell mass and glucose tolerance. |
| 1560 | 20947509 | In contrast, lack of Igf1r function in β cells aggravates the consequences of Irs2 ablation in double mutants and results in lethal diabetes by 6 weeks of age. |
| 1561 | 20947509 | This additivity of phenotypic manifestations indicates that Irs2 serves a pathway that is largely independent of Igf1r signaling. |
| 1562 | 20947509 | Consistent with the view that the latter is the InsR pathway, we show that combined β cell-specific knock-out of both Insr and Igf1r results in a phenocopy of double mutants lacking Igf1r and Irs2. |
| 1563 | 20947509 | We conclude that Igf1r signals primarily through Irs1 and affects insulin secretion, whereas β cell proliferation is mainly regulated by InsR using Irs2 as a downstream signaling effector. |
| 1564 | 20947509 | Genetic analysis of type-1 insulin-like growth factor receptor signaling through insulin receptor substrate-1 and -2 in pancreatic beta cells. |
| 1565 | 20947509 | Inactivation of insulin receptor (InsR), IGF1 receptor (Igf1r), or Irs1 in β cells impairs insulin secretion. |
| 1566 | 20947509 | To examine genetically the involvement of Irs1 and Irs2 in Igf1r signaling, we generated double mutant mice lacking Igf1r specifically in pancreatic β cells in an Irs1- or Irs2-null background. |
| 1567 | 20947509 | We show that Igf1r/Irs1 double mutants do not differ phenotypically from Irs1 single mutants and exhibit hyperinsulinemia, while maintaining normal β cell mass and glucose tolerance. |
| 1568 | 20947509 | In contrast, lack of Igf1r function in β cells aggravates the consequences of Irs2 ablation in double mutants and results in lethal diabetes by 6 weeks of age. |
| 1569 | 20947509 | This additivity of phenotypic manifestations indicates that Irs2 serves a pathway that is largely independent of Igf1r signaling. |
| 1570 | 20947509 | Consistent with the view that the latter is the InsR pathway, we show that combined β cell-specific knock-out of both Insr and Igf1r results in a phenocopy of double mutants lacking Igf1r and Irs2. |
| 1571 | 20947509 | We conclude that Igf1r signals primarily through Irs1 and affects insulin secretion, whereas β cell proliferation is mainly regulated by InsR using Irs2 as a downstream signaling effector. |
| 1572 | 20947509 | Genetic analysis of type-1 insulin-like growth factor receptor signaling through insulin receptor substrate-1 and -2 in pancreatic beta cells. |
| 1573 | 20947509 | Inactivation of insulin receptor (InsR), IGF1 receptor (Igf1r), or Irs1 in β cells impairs insulin secretion. |
| 1574 | 20947509 | To examine genetically the involvement of Irs1 and Irs2 in Igf1r signaling, we generated double mutant mice lacking Igf1r specifically in pancreatic β cells in an Irs1- or Irs2-null background. |
| 1575 | 20947509 | We show that Igf1r/Irs1 double mutants do not differ phenotypically from Irs1 single mutants and exhibit hyperinsulinemia, while maintaining normal β cell mass and glucose tolerance. |
| 1576 | 20947509 | In contrast, lack of Igf1r function in β cells aggravates the consequences of Irs2 ablation in double mutants and results in lethal diabetes by 6 weeks of age. |
| 1577 | 20947509 | This additivity of phenotypic manifestations indicates that Irs2 serves a pathway that is largely independent of Igf1r signaling. |
| 1578 | 20947509 | Consistent with the view that the latter is the InsR pathway, we show that combined β cell-specific knock-out of both Insr and Igf1r results in a phenocopy of double mutants lacking Igf1r and Irs2. |
| 1579 | 20947509 | We conclude that Igf1r signals primarily through Irs1 and affects insulin secretion, whereas β cell proliferation is mainly regulated by InsR using Irs2 as a downstream signaling effector. |
| 1580 | 20947509 | Genetic analysis of type-1 insulin-like growth factor receptor signaling through insulin receptor substrate-1 and -2 in pancreatic beta cells. |
| 1581 | 20947509 | Inactivation of insulin receptor (InsR), IGF1 receptor (Igf1r), or Irs1 in β cells impairs insulin secretion. |
| 1582 | 20947509 | To examine genetically the involvement of Irs1 and Irs2 in Igf1r signaling, we generated double mutant mice lacking Igf1r specifically in pancreatic β cells in an Irs1- or Irs2-null background. |
| 1583 | 20947509 | We show that Igf1r/Irs1 double mutants do not differ phenotypically from Irs1 single mutants and exhibit hyperinsulinemia, while maintaining normal β cell mass and glucose tolerance. |
| 1584 | 20947509 | In contrast, lack of Igf1r function in β cells aggravates the consequences of Irs2 ablation in double mutants and results in lethal diabetes by 6 weeks of age. |
| 1585 | 20947509 | This additivity of phenotypic manifestations indicates that Irs2 serves a pathway that is largely independent of Igf1r signaling. |
| 1586 | 20947509 | Consistent with the view that the latter is the InsR pathway, we show that combined β cell-specific knock-out of both Insr and Igf1r results in a phenocopy of double mutants lacking Igf1r and Irs2. |
| 1587 | 20947509 | We conclude that Igf1r signals primarily through Irs1 and affects insulin secretion, whereas β cell proliferation is mainly regulated by InsR using Irs2 as a downstream signaling effector. |
| 1588 | 20947509 | Genetic analysis of type-1 insulin-like growth factor receptor signaling through insulin receptor substrate-1 and -2 in pancreatic beta cells. |
| 1589 | 20947509 | Inactivation of insulin receptor (InsR), IGF1 receptor (Igf1r), or Irs1 in β cells impairs insulin secretion. |
| 1590 | 20947509 | To examine genetically the involvement of Irs1 and Irs2 in Igf1r signaling, we generated double mutant mice lacking Igf1r specifically in pancreatic β cells in an Irs1- or Irs2-null background. |
| 1591 | 20947509 | We show that Igf1r/Irs1 double mutants do not differ phenotypically from Irs1 single mutants and exhibit hyperinsulinemia, while maintaining normal β cell mass and glucose tolerance. |
| 1592 | 20947509 | In contrast, lack of Igf1r function in β cells aggravates the consequences of Irs2 ablation in double mutants and results in lethal diabetes by 6 weeks of age. |
| 1593 | 20947509 | This additivity of phenotypic manifestations indicates that Irs2 serves a pathway that is largely independent of Igf1r signaling. |
| 1594 | 20947509 | Consistent with the view that the latter is the InsR pathway, we show that combined β cell-specific knock-out of both Insr and Igf1r results in a phenocopy of double mutants lacking Igf1r and Irs2. |
| 1595 | 20947509 | We conclude that Igf1r signals primarily through Irs1 and affects insulin secretion, whereas β cell proliferation is mainly regulated by InsR using Irs2 as a downstream signaling effector. |
| 1596 | 20947509 | Genetic analysis of type-1 insulin-like growth factor receptor signaling through insulin receptor substrate-1 and -2 in pancreatic beta cells. |
| 1597 | 20947509 | Inactivation of insulin receptor (InsR), IGF1 receptor (Igf1r), or Irs1 in β cells impairs insulin secretion. |
| 1598 | 20947509 | To examine genetically the involvement of Irs1 and Irs2 in Igf1r signaling, we generated double mutant mice lacking Igf1r specifically in pancreatic β cells in an Irs1- or Irs2-null background. |
| 1599 | 20947509 | We show that Igf1r/Irs1 double mutants do not differ phenotypically from Irs1 single mutants and exhibit hyperinsulinemia, while maintaining normal β cell mass and glucose tolerance. |
| 1600 | 20947509 | In contrast, lack of Igf1r function in β cells aggravates the consequences of Irs2 ablation in double mutants and results in lethal diabetes by 6 weeks of age. |
| 1601 | 20947509 | This additivity of phenotypic manifestations indicates that Irs2 serves a pathway that is largely independent of Igf1r signaling. |
| 1602 | 20947509 | Consistent with the view that the latter is the InsR pathway, we show that combined β cell-specific knock-out of both Insr and Igf1r results in a phenocopy of double mutants lacking Igf1r and Irs2. |
| 1603 | 20947509 | We conclude that Igf1r signals primarily through Irs1 and affects insulin secretion, whereas β cell proliferation is mainly regulated by InsR using Irs2 as a downstream signaling effector. |
| 1604 | 20947509 | Genetic analysis of type-1 insulin-like growth factor receptor signaling through insulin receptor substrate-1 and -2 in pancreatic beta cells. |
| 1605 | 20947509 | Inactivation of insulin receptor (InsR), IGF1 receptor (Igf1r), or Irs1 in β cells impairs insulin secretion. |
| 1606 | 20947509 | To examine genetically the involvement of Irs1 and Irs2 in Igf1r signaling, we generated double mutant mice lacking Igf1r specifically in pancreatic β cells in an Irs1- or Irs2-null background. |
| 1607 | 20947509 | We show that Igf1r/Irs1 double mutants do not differ phenotypically from Irs1 single mutants and exhibit hyperinsulinemia, while maintaining normal β cell mass and glucose tolerance. |
| 1608 | 20947509 | In contrast, lack of Igf1r function in β cells aggravates the consequences of Irs2 ablation in double mutants and results in lethal diabetes by 6 weeks of age. |
| 1609 | 20947509 | This additivity of phenotypic manifestations indicates that Irs2 serves a pathway that is largely independent of Igf1r signaling. |
| 1610 | 20947509 | Consistent with the view that the latter is the InsR pathway, we show that combined β cell-specific knock-out of both Insr and Igf1r results in a phenocopy of double mutants lacking Igf1r and Irs2. |
| 1611 | 20947509 | We conclude that Igf1r signals primarily through Irs1 and affects insulin secretion, whereas β cell proliferation is mainly regulated by InsR using Irs2 as a downstream signaling effector. |
| 1612 | 20948845 | Although the mortality attributable to cancer in type 2 diabetes is overshadowed by that due to cardiovascular disease, emerging data from epidemiologic studies suggest that insulin therapy may confer added risk for cancer, perhaps mediated by signaling through the IGF-1 (insulin-like growth factor-1) receptor. |
| 1613 | 21031338 | It could be shown that the applied anabolic combination significantly influenced the expression of the steroid receptor ERα, the keratinization factor CK8, the proinflammatory interleukins IL-1α and IL-1β, the growth factors FGF7, EGF, EGFR, IGF-1R, TGFα and LTF, the oncogen c-jun and other factors like actinβ and ubiquitin 3. |
| 1614 | 21139139 | A kinase-independent role for unoccupied insulin and IGF-1 receptors in the control of apoptosis. |
| 1615 | 21139139 | Insulin and insulin-like growth factor 1 (IGF-1) act as antiapoptotic hormones. |
| 1616 | 21139139 | We found that, unexpectedly, double-knockout (DKO) cells that lacked both insulin and IGF-1 receptors (IR and IGF1R, respectively) were resistant to apoptosis induced through either the intrinsic or the extrinsic pathway. |
| 1617 | 21139139 | This resistance to apoptosis was associated with decreased abundance of the proapoptotic protein Bax and increases in abundance of the antiapoptotic proteins Bcl-2, Bcl-xL, XIAP, and Flip. |
| 1618 | 21139139 | Insulin and IGF-1 binding stimulates receptor tyrosine kinase activity and blocks apoptosis, whereas unliganded IR and IGF1R, acting through a mechanism independent of their catalytic activity, exert a permissive effect on cell death. |
| 1619 | 21139139 | A kinase-independent role for unoccupied insulin and IGF-1 receptors in the control of apoptosis. |
| 1620 | 21139139 | Insulin and insulin-like growth factor 1 (IGF-1) act as antiapoptotic hormones. |
| 1621 | 21139139 | We found that, unexpectedly, double-knockout (DKO) cells that lacked both insulin and IGF-1 receptors (IR and IGF1R, respectively) were resistant to apoptosis induced through either the intrinsic or the extrinsic pathway. |
| 1622 | 21139139 | This resistance to apoptosis was associated with decreased abundance of the proapoptotic protein Bax and increases in abundance of the antiapoptotic proteins Bcl-2, Bcl-xL, XIAP, and Flip. |
| 1623 | 21139139 | Insulin and IGF-1 binding stimulates receptor tyrosine kinase activity and blocks apoptosis, whereas unliganded IR and IGF1R, acting through a mechanism independent of their catalytic activity, exert a permissive effect on cell death. |
| 1624 | 21239445 | IGF-I induces skeletal muscle hypertrophy by stimulating protein synthesis and suppressing the protein degradation pathway; the downstream signaling pathways Akt-mammalian target of rapamycin (mTOR)-p70-kDA-S6-kinase (p70S6K), and Forkhead box O1 (FoxO1) play essential roles in this regulation. |
| 1625 | 21239445 | While treatment with H(2)O(2) significantly enhanced IGF-I-induced phosphorylation of the IGF-I receptor (IGF-IR), IGF-IR phosphorylation was markedly attenuated when cells were treated with antioxidants. |
| 1626 | 21239445 | Furthermore, the phosphorylation of FoxO1 by IGF-I decreased concomitantly with the restoration of the expression of its target genes, Atrogin-1 and muscle RING finger 1, which are related to muscle atrophy. |
| 1627 | 21239445 | Nox4 knockdown, which is reportedly to produce ROS in insulin signaling, attenuated IGF-I-induced IGF-IR phosphorylation, indicating that Nox4 is involved in the regulation of IGF-I signaling. |
| 1628 | 21239445 | IGF-I induces skeletal muscle hypertrophy by stimulating protein synthesis and suppressing the protein degradation pathway; the downstream signaling pathways Akt-mammalian target of rapamycin (mTOR)-p70-kDA-S6-kinase (p70S6K), and Forkhead box O1 (FoxO1) play essential roles in this regulation. |
| 1629 | 21239445 | While treatment with H(2)O(2) significantly enhanced IGF-I-induced phosphorylation of the IGF-I receptor (IGF-IR), IGF-IR phosphorylation was markedly attenuated when cells were treated with antioxidants. |
| 1630 | 21239445 | Furthermore, the phosphorylation of FoxO1 by IGF-I decreased concomitantly with the restoration of the expression of its target genes, Atrogin-1 and muscle RING finger 1, which are related to muscle atrophy. |
| 1631 | 21239445 | Nox4 knockdown, which is reportedly to produce ROS in insulin signaling, attenuated IGF-I-induced IGF-IR phosphorylation, indicating that Nox4 is involved in the regulation of IGF-I signaling. |
| 1632 | 21330367 | Insulin-like growth factor 1-mediated hyperthermia involves anterior hypothalamic insulin receptors. |
| 1633 | 21330367 | The objective is to investigate the role of insulin-like growth factor 1 (IGF-1) in the regulation of core body temperature. |
| 1634 | 21330367 | Sequencing cDNA libraries from individual warm-sensitive neurons from the preoptic area (POA) of the hypothalamus, a region involved in the central control of thermoregulation, identified neurons that express both IGF-1 receptor (IGF-1R) and insulin receptor transcripts. |
| 1635 | 21330367 | IGF-1 injection into the POA caused dose-dependent hyperthermia that could be blocked by pretreatment with the IGF-1R tyrosine kinase inhibitor, PQ401. |
| 1636 | 21330367 | Transgenic mice that lack neuronal insulin receptor expression in the brain (NIRKO mice) were unable to mount the full hyperthermic response to IGF-1, suggesting that the IGF-1 mediated hyperthermia is partly dependent on expression of functional neuronal insulin receptors. |
| 1637 | 21330367 | These data indicate a novel thermoregulatory role for both IGF-1R and neuronal insulin receptors in IGF-1 activation of BAT and hyperthermia. |
| 1638 | 21330367 | Insulin-like growth factor 1-mediated hyperthermia involves anterior hypothalamic insulin receptors. |
| 1639 | 21330367 | The objective is to investigate the role of insulin-like growth factor 1 (IGF-1) in the regulation of core body temperature. |
| 1640 | 21330367 | Sequencing cDNA libraries from individual warm-sensitive neurons from the preoptic area (POA) of the hypothalamus, a region involved in the central control of thermoregulation, identified neurons that express both IGF-1 receptor (IGF-1R) and insulin receptor transcripts. |
| 1641 | 21330367 | IGF-1 injection into the POA caused dose-dependent hyperthermia that could be blocked by pretreatment with the IGF-1R tyrosine kinase inhibitor, PQ401. |
| 1642 | 21330367 | Transgenic mice that lack neuronal insulin receptor expression in the brain (NIRKO mice) were unable to mount the full hyperthermic response to IGF-1, suggesting that the IGF-1 mediated hyperthermia is partly dependent on expression of functional neuronal insulin receptors. |
| 1643 | 21330367 | These data indicate a novel thermoregulatory role for both IGF-1R and neuronal insulin receptors in IGF-1 activation of BAT and hyperthermia. |
| 1644 | 21330367 | Insulin-like growth factor 1-mediated hyperthermia involves anterior hypothalamic insulin receptors. |
| 1645 | 21330367 | The objective is to investigate the role of insulin-like growth factor 1 (IGF-1) in the regulation of core body temperature. |
| 1646 | 21330367 | Sequencing cDNA libraries from individual warm-sensitive neurons from the preoptic area (POA) of the hypothalamus, a region involved in the central control of thermoregulation, identified neurons that express both IGF-1 receptor (IGF-1R) and insulin receptor transcripts. |
| 1647 | 21330367 | IGF-1 injection into the POA caused dose-dependent hyperthermia that could be blocked by pretreatment with the IGF-1R tyrosine kinase inhibitor, PQ401. |
| 1648 | 21330367 | Transgenic mice that lack neuronal insulin receptor expression in the brain (NIRKO mice) were unable to mount the full hyperthermic response to IGF-1, suggesting that the IGF-1 mediated hyperthermia is partly dependent on expression of functional neuronal insulin receptors. |
| 1649 | 21330367 | These data indicate a novel thermoregulatory role for both IGF-1R and neuronal insulin receptors in IGF-1 activation of BAT and hyperthermia. |
| 1650 | 21372039 | Abnormal activation of the insulin-like growth factor (IGF)/ IGF-1 receptor (IGF-1R) axis is also involved in obesity-related liver tumorigenesis. |
| 1651 | 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. |
| 1652 | 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. |
| 1653 | 21372039 | Abnormal activation of the insulin-like growth factor (IGF)/ IGF-1 receptor (IGF-1R) axis is also involved in obesity-related liver tumorigenesis. |
| 1654 | 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. |
| 1655 | 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. |
| 1656 | 21379576 | MKR mice, lacking insulin-like growth factor 1 receptor (IGF-1R) signaling in skeletal muscle, are lean yet hyperlipidemic, hyperinsulinemic, and hyperglycemic, with severe insulin resistance and elevated hepatic and skeletal muscle levels of triglycerides. |
| 1657 | 21379576 | We have previously shown that chronic peripheral administration of the adipokine leptin improves hepatic insulin sensitivity in these mice independently of its effects on food intake. |
| 1658 | 21379576 | Central leptin significantly reduced food intake, body weight gain and adiposity, as well as serum glucose, insulin, leptin, free fatty acid and triglyceride levels relative to ACSF treated controls. |
| 1659 | 21379576 | Central leptin also improved glucose tolerance and hepatic insulin sensitivity determined using the euglycemic-hyperinsulinemic clamps relative to pair fed vehicle treated controls, as well as increasing the rate of glucose disappearance. |
| 1660 | 21379576 | These results demonstrate that central leptin dramatically improves insulin sensitivity independently of its effects on food intake, in a lean mouse model of type 2 diabetes. |
| 1661 | 21474992 | Epigenetic DNA methylation in the promoters of the Igf1 receptor and insulin receptor genes in db/db mice. |
| 1662 | 21474992 | We have investigated promoter methylation of the Insr, Igf1 and Igf1r genes in skeletal and cardiac muscles of normal and diabetic db/db mice. |
| 1663 | 21474992 | Epigenetic DNA methylation in the promoters of the Igf1 receptor and insulin receptor genes in db/db mice. |
| 1664 | 21474992 | We have investigated promoter methylation of the Insr, Igf1 and Igf1r genes in skeletal and cardiac muscles of normal and diabetic db/db mice. |
| 1665 | 21567076 | Insulin-dependent diabetes mellitus decreases osteoblastogenesis associated with the inhibition of Wnt signaling through increased expression of Sost and Dkk1 and inhibition of Akt activation. |
| 1666 | 21567076 | Insulin-dependent diabetes mellitus (IDDM) is known to be associated with an increased risk of osteopenia. |
| 1667 | 21567076 | After 4 weeks, the diabetic rats exhibited bone loss, low levels of osteocalcin, insulin-like growth factor-I (IGF-I) and bone alkaline phosphatase (ALP) activity with normal levels of bone tartrate-resistant acid phosphatase (TRAP) and cathepsin K activity, and urinary excretion of deoxypyridinoline (Dpd). |
| 1668 | 21567076 | The decreased expression of ALP, osteoclacin and collagen mRNA was associated with a decrease in the expression of runt-related transcription factor 2 (Runx2), Osterix and distal-less homeobox 5 (Dlx5) and an unaltered expression of bone morphogenic protein-2 (BMP2). |
| 1669 | 21567076 | The protein levels of Runx2, phosphorylated glycogen synthase kinase 3β (GSK3β), active β-catenin and β-catenin decreased. |
| 1670 | 21567076 | The mRNA and protein levels of sclerosteosis (Sost) and Dickkopf 1 (Dkk1), inhibitors of Wnt signaling, increased. |
| 1671 | 21567076 | The mRNA expression of IGF-I and the IGF-I receptor (IGF-IR) was suppressed. |
| 1672 | 21567076 | These changes observed in the bone of diabetic rats were reversed by treatment with insulin, but not by normalization of the circulating IGF-I levels by treatment with IGF-I. |
| 1673 | 21567076 | These results suggest that insulin-deficiency in IDDM decreases osteoblastogenesis associated with inhibition of Wnt signaling through the increased expression of Sost and Dkk1 and the inhibition of Akt activation. |
| 1674 | 21677284 | The insulin-like growth factor-1 receptor is a negative regulator of nitric oxide bioavailability and insulin sensitivity in the endothelium. |
| 1675 | 21715431 | Insulin-like growth factor 1 receptor (IGF1R) has been proposed as a second autoantigen in complications of GD such as orbitopathy. |
| 1676 | 21715431 | We attempted to induce orbital tissue remodeling in mice undergoing immunizations with plasmids encoding TSHR and IGF1R delivered by in vivo skeletal muscle electroporation, a procedure known to give a sustained, long-term antibody response. |
| 1677 | 21715431 | Our findings imply that immunization with TSHR A-subunit plasmid leads to generation of IGF1R antibodies, which together with thyroid-stimulating antibodies may precipitate remodeling of orbital tissue, raising our understanding of its close association with GD. |
| 1678 | 21715431 | Insulin-like growth factor 1 receptor (IGF1R) has been proposed as a second autoantigen in complications of GD such as orbitopathy. |
| 1679 | 21715431 | We attempted to induce orbital tissue remodeling in mice undergoing immunizations with plasmids encoding TSHR and IGF1R delivered by in vivo skeletal muscle electroporation, a procedure known to give a sustained, long-term antibody response. |
| 1680 | 21715431 | Our findings imply that immunization with TSHR A-subunit plasmid leads to generation of IGF1R antibodies, which together with thyroid-stimulating antibodies may precipitate remodeling of orbital tissue, raising our understanding of its close association with GD. |
| 1681 | 21715431 | Insulin-like growth factor 1 receptor (IGF1R) has been proposed as a second autoantigen in complications of GD such as orbitopathy. |
| 1682 | 21715431 | We attempted to induce orbital tissue remodeling in mice undergoing immunizations with plasmids encoding TSHR and IGF1R delivered by in vivo skeletal muscle electroporation, a procedure known to give a sustained, long-term antibody response. |
| 1683 | 21715431 | Our findings imply that immunization with TSHR A-subunit plasmid leads to generation of IGF1R antibodies, which together with thyroid-stimulating antibodies may precipitate remodeling of orbital tissue, raising our understanding of its close association with GD. |
| 1684 | 21761363 | The insulin analog glargine has a higher binding affinity than regular insulin for the insulin-like growth factor 1 receptor in vitro, raising questions about increased mitogenicity in vivo. |
| 1685 | 21761363 | We assessed epithelial proliferation after long-term insulin treatment (18 weeks) by 5-bromo-2'-deoxyuridine and Ki67 staining and analyzed the formation of aberrant crypt foci (ACF) in mice treated with insulin glargine or NPH insulin or 10 weeks after initiation with 1,2-dimethylhydrazine. |
| 1686 | 21776823 | Molecular and cellular studies indicated that metformin significantly elevated p53 and Bax levels and reduced STAT3 and Bcl-2. |
| 1687 | 21776823 | Receptor inhibitor studies indicated that p53 activation was mediated through insulin receptor (IR), not insulin-like growth factor-1 receptor (IGF-IR). |
| 1688 | 21776823 | Furthermore, MEK inhibitor significantly suppressed metformin-induced p53 and Bax elevation while ERK inhibitor generated a slight reduction in p53 levels. |
| 1689 | 21776823 | In contrast, PI3K inhibitor did not produce any effect on the metformin-elevated p53 levels. |
| 1690 | 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. |
| 1691 | 21776823 | All these results suggested that metformin activated p53, Bax, and induced tumor cell apoptosis through the ERK signaling pathway. |
| 1692 | 21776823 | This pathway has not been previously described for IR, p53, Bax activation, or apoptosis. |
| 1693 | 21826649 | ARPE-19 cells cultured in high-glucose (HG) medium or under hypoxia (1% oxygen)-induced phosphorylation of the stress-activated kinases JNK and p38 MAPK. |
| 1694 | 21826649 | Likewise, hyperglycemia and hypoxia triggered the phosphorylation of the endoplasmic reticulum (ER) stress markers PERK and eIF2α and the induction of the pro-apoptotic transcription factor CHOP. |
| 1695 | 21826649 | FA increased insulin-like growth factor I receptor (IGF-IR)-mediated survival signaling in cells cultured under hyperglycemia and hypoxia, thereby suppressing caspase-3 activation and down-regulation of BclxL. |
| 1696 | 22057897 | Insulin receptor signaling mediates APP processing and β-amyloid accumulation without altering survival in a transgenic mouse model of Alzheimer's disease. |
| 1697 | 22057897 | In brains from patients with Alzheimer's disease (AD), expression of insulin receptor (IR), insulin-like growth factor-1 receptor (IGF-1R), and insulin receptor substrate proteins is downregulated. |
| 1698 | 22057897 | A key step in the pathogenesis of AD is the accumulation of amyloid precursor protein (APP) cleavage products, β-amyloid (Aβ)(1-42) and Aβ(1-40). |
| 1699 | 22057897 | Analyzing APP C-terminal fragments (CTF) revealed decreased α-/β-CTFs in the brains of nIR(-/-)Tg2576 mice suggesting decreased APP processing. |
| 1700 | 22057897 | Cell based experiments showed that inhibition of the PI3-kinase pathway suppresses endosomal APP cleavage and decreases α- as well as β-secretase activity. |
| 1701 | 22057897 | Deletion of only one copy of the neuronal IGF-1R partially rescues the premature mortality of Tg2576 mice without altering total amyloid load. |
| 1702 | 22057897 | Analysis of Tg2576 mice expressing either a dominant negative or constitutively active form of forkhead box-O (FoxO)1 did not reveal any alteration of amyloid burden, APP processing and did not rescue premature mortality in these mice. |
| 1703 | 22057897 | But exclusively decreased IGF-1R expression reduces AD-associated mortality independent of β-amyloid accumulation and FoxO1-mediated transcription. |
| 1704 | 22057897 | Insulin receptor signaling mediates APP processing and β-amyloid accumulation without altering survival in a transgenic mouse model of Alzheimer's disease. |
| 1705 | 22057897 | In brains from patients with Alzheimer's disease (AD), expression of insulin receptor (IR), insulin-like growth factor-1 receptor (IGF-1R), and insulin receptor substrate proteins is downregulated. |
| 1706 | 22057897 | A key step in the pathogenesis of AD is the accumulation of amyloid precursor protein (APP) cleavage products, β-amyloid (Aβ)(1-42) and Aβ(1-40). |
| 1707 | 22057897 | Analyzing APP C-terminal fragments (CTF) revealed decreased α-/β-CTFs in the brains of nIR(-/-)Tg2576 mice suggesting decreased APP processing. |
| 1708 | 22057897 | Cell based experiments showed that inhibition of the PI3-kinase pathway suppresses endosomal APP cleavage and decreases α- as well as β-secretase activity. |
| 1709 | 22057897 | Deletion of only one copy of the neuronal IGF-1R partially rescues the premature mortality of Tg2576 mice without altering total amyloid load. |
| 1710 | 22057897 | Analysis of Tg2576 mice expressing either a dominant negative or constitutively active form of forkhead box-O (FoxO)1 did not reveal any alteration of amyloid burden, APP processing and did not rescue premature mortality in these mice. |
| 1711 | 22057897 | But exclusively decreased IGF-1R expression reduces AD-associated mortality independent of β-amyloid accumulation and FoxO1-mediated transcription. |
| 1712 | 22057897 | Insulin receptor signaling mediates APP processing and β-amyloid accumulation without altering survival in a transgenic mouse model of Alzheimer's disease. |
| 1713 | 22057897 | In brains from patients with Alzheimer's disease (AD), expression of insulin receptor (IR), insulin-like growth factor-1 receptor (IGF-1R), and insulin receptor substrate proteins is downregulated. |
| 1714 | 22057897 | A key step in the pathogenesis of AD is the accumulation of amyloid precursor protein (APP) cleavage products, β-amyloid (Aβ)(1-42) and Aβ(1-40). |
| 1715 | 22057897 | Analyzing APP C-terminal fragments (CTF) revealed decreased α-/β-CTFs in the brains of nIR(-/-)Tg2576 mice suggesting decreased APP processing. |
| 1716 | 22057897 | Cell based experiments showed that inhibition of the PI3-kinase pathway suppresses endosomal APP cleavage and decreases α- as well as β-secretase activity. |
| 1717 | 22057897 | Deletion of only one copy of the neuronal IGF-1R partially rescues the premature mortality of Tg2576 mice without altering total amyloid load. |
| 1718 | 22057897 | Analysis of Tg2576 mice expressing either a dominant negative or constitutively active form of forkhead box-O (FoxO)1 did not reveal any alteration of amyloid burden, APP processing and did not rescue premature mortality in these mice. |
| 1719 | 22057897 | But exclusively decreased IGF-1R expression reduces AD-associated mortality independent of β-amyloid accumulation and FoxO1-mediated transcription. |
| 1720 | 22087027 | The type 1 insulin-like growth factor receptor (IGF-IR) pathway is mandatory for the follistatin-induced skeletal muscle hypertrophy. |
| 1721 | 22087027 | Myostatin inhibition by follistatin (FS) offers a new approach for muscle mass enhancement. |
| 1722 | 22087027 | Because IGF-I and IGF-II, two crucial skeletal muscle growth factors, are induced by myostatin inhibition, we assessed their role in FS action. |
| 1723 | 22087027 | We then tested the role of the signaling molecules stimulated by IGF-IR, in particular the Akt/mammalian target of rapamycin (mTOR)/70-kDa ribosomal protein S6 kinase (S6K) pathway. |
| 1724 | 22087027 | In conclusion, the IGF-IR/Akt/mTOR pathway plays a critical role in FS-induced muscle hypertrophy. |
| 1725 | 22087027 | In contrast, induction of IGF-II expression and S6K activity by FS are not required for the hypertrophic action of FS. |
| 1726 | 22087027 | The type 1 insulin-like growth factor receptor (IGF-IR) pathway is mandatory for the follistatin-induced skeletal muscle hypertrophy. |
| 1727 | 22087027 | Myostatin inhibition by follistatin (FS) offers a new approach for muscle mass enhancement. |
| 1728 | 22087027 | Because IGF-I and IGF-II, two crucial skeletal muscle growth factors, are induced by myostatin inhibition, we assessed their role in FS action. |
| 1729 | 22087027 | We then tested the role of the signaling molecules stimulated by IGF-IR, in particular the Akt/mammalian target of rapamycin (mTOR)/70-kDa ribosomal protein S6 kinase (S6K) pathway. |
| 1730 | 22087027 | In conclusion, the IGF-IR/Akt/mTOR pathway plays a critical role in FS-induced muscle hypertrophy. |
| 1731 | 22087027 | In contrast, induction of IGF-II expression and S6K activity by FS are not required for the hypertrophic action of FS. |
| 1732 | 22087027 | The type 1 insulin-like growth factor receptor (IGF-IR) pathway is mandatory for the follistatin-induced skeletal muscle hypertrophy. |
| 1733 | 22087027 | Myostatin inhibition by follistatin (FS) offers a new approach for muscle mass enhancement. |
| 1734 | 22087027 | Because IGF-I and IGF-II, two crucial skeletal muscle growth factors, are induced by myostatin inhibition, we assessed their role in FS action. |
| 1735 | 22087027 | We then tested the role of the signaling molecules stimulated by IGF-IR, in particular the Akt/mammalian target of rapamycin (mTOR)/70-kDa ribosomal protein S6 kinase (S6K) pathway. |
| 1736 | 22087027 | In conclusion, the IGF-IR/Akt/mTOR pathway plays a critical role in FS-induced muscle hypertrophy. |
| 1737 | 22087027 | In contrast, induction of IGF-II expression and S6K activity by FS are not required for the hypertrophic action of FS. |
| 1738 | 22130793 | Severe short stature caused by novel compound heterozygous mutations of the insulin-like growth factor 1 receptor (IGF1R). |
| 1739 | 22198814 | Neuron-specific deletion of a single copy of the insulin-like growth factor-1 receptor gene reduces fat accumulation during aging. |
| 1740 | 22198814 | Insulin, insulin-like growth factor-1 (IGF-1), and leptin signaling have been proposed to play an important role in regulating energy homeostasis. |
| 1741 | 22198814 | In order to specifically address the role of neuronal IGF-1 receptor (IGF-1R) signaling for energy expenditure and metabolism we used conditional mutagenesis. |
| 1742 | 22198814 | Surprisingly, serum IGF-1 and IGF-1 binding protein 3 (IGF-BP3) concentrations were decreased in nIGF-1R(+/-) mice despite the presence of normal pituitaries suggesting a functional feedback mechanism via neuronal IGF-1Rs, which regulate serum IGF-1 levels. |
| 1743 | 22198814 | Neuron-specific deletion of a single copy of the insulin-like growth factor-1 receptor gene reduces fat accumulation during aging. |
| 1744 | 22198814 | Insulin, insulin-like growth factor-1 (IGF-1), and leptin signaling have been proposed to play an important role in regulating energy homeostasis. |
| 1745 | 22198814 | In order to specifically address the role of neuronal IGF-1 receptor (IGF-1R) signaling for energy expenditure and metabolism we used conditional mutagenesis. |
| 1746 | 22198814 | Surprisingly, serum IGF-1 and IGF-1 binding protein 3 (IGF-BP3) concentrations were decreased in nIGF-1R(+/-) mice despite the presence of normal pituitaries suggesting a functional feedback mechanism via neuronal IGF-1Rs, which regulate serum IGF-1 levels. |
| 1747 | 22223845 | The mRNA expression of insulin-like growth factor-1 receptor (IGF-1R, P<0.01) was increased in the MSG-AOM mice, when compared with the mice given AOM alone. |
| 1748 | 22341695 | Exercise training enhances cardiac IGFI-R/PI3K/Akt and Bcl-2 family associated pro-survival pathways in streptozotocin-induced diabetic rats. |
| 1749 | 22482470 | To determine the ratio of IGFBP3:IGF-1 in normal and diabetic human tears, and in telomerase-immortalized human corneal epithelial cells (hTCEpi) cultured under elevated glucose conditions and to correlate these changes with total and phosphorylated levels of IGF-1R. |
| 1750 | 22482470 | IGFBP3, IGF-1, and phosphorylated IGF-1R levels were assessed by ELISA. |
| 1751 | 22482470 | IGFBP3 and IGF-1R mRNA were assessed by real-time polymerase chain reaction (PCR). |
| 1752 | 22482470 | The increase in the IGFBP3:IGF-1 ratio detected in diabetic tears compared to normal controls blocked phosphorylation of the IGF-1R by IGF-1 (P<0.001) when tested in vitro. |
| 1753 | 22482470 | Taken together, these in vivo and confirmatory in vitro findings suggest that the observed increase in IGFBP3 found in human tears may attenuate IGF-1R signaling in the diabetic cornea. |
| 1754 | 22482470 | To determine the ratio of IGFBP3:IGF-1 in normal and diabetic human tears, and in telomerase-immortalized human corneal epithelial cells (hTCEpi) cultured under elevated glucose conditions and to correlate these changes with total and phosphorylated levels of IGF-1R. |
| 1755 | 22482470 | IGFBP3, IGF-1, and phosphorylated IGF-1R levels were assessed by ELISA. |
| 1756 | 22482470 | IGFBP3 and IGF-1R mRNA were assessed by real-time polymerase chain reaction (PCR). |
| 1757 | 22482470 | The increase in the IGFBP3:IGF-1 ratio detected in diabetic tears compared to normal controls blocked phosphorylation of the IGF-1R by IGF-1 (P<0.001) when tested in vitro. |
| 1758 | 22482470 | Taken together, these in vivo and confirmatory in vitro findings suggest that the observed increase in IGFBP3 found in human tears may attenuate IGF-1R signaling in the diabetic cornea. |
| 1759 | 22482470 | To determine the ratio of IGFBP3:IGF-1 in normal and diabetic human tears, and in telomerase-immortalized human corneal epithelial cells (hTCEpi) cultured under elevated glucose conditions and to correlate these changes with total and phosphorylated levels of IGF-1R. |
| 1760 | 22482470 | IGFBP3, IGF-1, and phosphorylated IGF-1R levels were assessed by ELISA. |
| 1761 | 22482470 | IGFBP3 and IGF-1R mRNA were assessed by real-time polymerase chain reaction (PCR). |
| 1762 | 22482470 | The increase in the IGFBP3:IGF-1 ratio detected in diabetic tears compared to normal controls blocked phosphorylation of the IGF-1R by IGF-1 (P<0.001) when tested in vitro. |
| 1763 | 22482470 | Taken together, these in vivo and confirmatory in vitro findings suggest that the observed increase in IGFBP3 found in human tears may attenuate IGF-1R signaling in the diabetic cornea. |
| 1764 | 22482470 | To determine the ratio of IGFBP3:IGF-1 in normal and diabetic human tears, and in telomerase-immortalized human corneal epithelial cells (hTCEpi) cultured under elevated glucose conditions and to correlate these changes with total and phosphorylated levels of IGF-1R. |
| 1765 | 22482470 | IGFBP3, IGF-1, and phosphorylated IGF-1R levels were assessed by ELISA. |
| 1766 | 22482470 | IGFBP3 and IGF-1R mRNA were assessed by real-time polymerase chain reaction (PCR). |
| 1767 | 22482470 | The increase in the IGFBP3:IGF-1 ratio detected in diabetic tears compared to normal controls blocked phosphorylation of the IGF-1R by IGF-1 (P<0.001) when tested in vitro. |
| 1768 | 22482470 | Taken together, these in vivo and confirmatory in vitro findings suggest that the observed increase in IGFBP3 found in human tears may attenuate IGF-1R signaling in the diabetic cornea. |
| 1769 | 22482470 | To determine the ratio of IGFBP3:IGF-1 in normal and diabetic human tears, and in telomerase-immortalized human corneal epithelial cells (hTCEpi) cultured under elevated glucose conditions and to correlate these changes with total and phosphorylated levels of IGF-1R. |
| 1770 | 22482470 | IGFBP3, IGF-1, and phosphorylated IGF-1R levels were assessed by ELISA. |
| 1771 | 22482470 | IGFBP3 and IGF-1R mRNA were assessed by real-time polymerase chain reaction (PCR). |
| 1772 | 22482470 | The increase in the IGFBP3:IGF-1 ratio detected in diabetic tears compared to normal controls blocked phosphorylation of the IGF-1R by IGF-1 (P<0.001) when tested in vitro. |
| 1773 | 22482470 | Taken together, these in vivo and confirmatory in vitro findings suggest that the observed increase in IGFBP3 found in human tears may attenuate IGF-1R signaling in the diabetic cornea. |
| 1774 | 22589390 | Insulin-like growth factor (IGF-I) signaling has been implicated to play an important role in regulation of cardiac growth, hypertrophy, and contractile function and has been linked to the development of age-related congestive heart failure. |
| 1775 | 22589390 | To investigate the effects of IGF-I signaling in the adult heart without confounding effects due to IGF-I overexpression or adaptation during embryonic and early postnatal development, we inactivated the IGF-I receptor (IGF-IR) by a 4-hydroxytamoxifen-inducible Cre recombinase in adult cardiac myocytes. |
| 1776 | 22589390 | Efficient inactivation of the IGF-IR (iCMIGF-IRKO) as assessed by Western analysis and real-time PCR went along with reduced IGF-I-dependent Akt and GSK3β phosphorylation. |
| 1777 | 22589390 | To address the question whether insulin signaling might compensate for the defective IGF-IR signaling, we inactivated β-cells by streptozotocin. |
| 1778 | 22589390 | Insulin-like growth factor (IGF-I) signaling has been implicated to play an important role in regulation of cardiac growth, hypertrophy, and contractile function and has been linked to the development of age-related congestive heart failure. |
| 1779 | 22589390 | To investigate the effects of IGF-I signaling in the adult heart without confounding effects due to IGF-I overexpression or adaptation during embryonic and early postnatal development, we inactivated the IGF-I receptor (IGF-IR) by a 4-hydroxytamoxifen-inducible Cre recombinase in adult cardiac myocytes. |
| 1780 | 22589390 | Efficient inactivation of the IGF-IR (iCMIGF-IRKO) as assessed by Western analysis and real-time PCR went along with reduced IGF-I-dependent Akt and GSK3β phosphorylation. |
| 1781 | 22589390 | To address the question whether insulin signaling might compensate for the defective IGF-IR signaling, we inactivated β-cells by streptozotocin. |
| 1782 | 22589390 | Insulin-like growth factor (IGF-I) signaling has been implicated to play an important role in regulation of cardiac growth, hypertrophy, and contractile function and has been linked to the development of age-related congestive heart failure. |
| 1783 | 22589390 | To investigate the effects of IGF-I signaling in the adult heart without confounding effects due to IGF-I overexpression or adaptation during embryonic and early postnatal development, we inactivated the IGF-I receptor (IGF-IR) by a 4-hydroxytamoxifen-inducible Cre recombinase in adult cardiac myocytes. |
| 1784 | 22589390 | Efficient inactivation of the IGF-IR (iCMIGF-IRKO) as assessed by Western analysis and real-time PCR went along with reduced IGF-I-dependent Akt and GSK3β phosphorylation. |
| 1785 | 22589390 | To address the question whether insulin signaling might compensate for the defective IGF-IR signaling, we inactivated β-cells by streptozotocin. |
| 1786 | 22654904 | Interestingly, studies in rodents suggest that reduced insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF-1R) signaling decrease AD pathology, that is, β-amyloid toxicity. |
| 1787 | 22654904 | In the mammalian brain, there are FoxO1, FoxO3a, and FoxO6 expressed. |
| 1788 | 22654904 | Surprisingly, high-fat diet specifically reduces the expression of FoxO3a and FoxO6 suggesting that IR/IGF-1 → FoxO-mediated transcription is involved in the pathogenesis of obesity-associated cognitive impairment. |
| 1789 | 22654904 | Therefore, the function of FoxO1 and FoxO3a has been investigated in animal models of Alzheimer's disease in detail. |
| 1790 | 22733797 | We recently demonstrated that reducing IGF-1 receptor (IGF-1R) numbers in the endothelium enhances nitric oxide (NO) bioavailability and endothelial cell insulin sensitivity. |
| 1791 | 22733797 | To examine the effect of increasing IGF-1R in the endothelium, we generated mice overexpressing human IGF-1R in the endothelium (human IGF-1R endothelium-overexpressing mice [hIGFREO]) under direction of the Tie2 promoter enhancer. hIGFREO aorta had reduced basal NO bioavailability (percent constriction to N(G)-monomethyl-l-arginine [mean (SEM) wild type 106% (30%); hIGFREO 48% (10%)]; P < 0.05). |
| 1792 | 22733797 | We recently demonstrated that reducing IGF-1 receptor (IGF-1R) numbers in the endothelium enhances nitric oxide (NO) bioavailability and endothelial cell insulin sensitivity. |
| 1793 | 22733797 | To examine the effect of increasing IGF-1R in the endothelium, we generated mice overexpressing human IGF-1R in the endothelium (human IGF-1R endothelium-overexpressing mice [hIGFREO]) under direction of the Tie2 promoter enhancer. hIGFREO aorta had reduced basal NO bioavailability (percent constriction to N(G)-monomethyl-l-arginine [mean (SEM) wild type 106% (30%); hIGFREO 48% (10%)]; P < 0.05). |
| 1794 | 23292283 | These changes may be partially related to impaired insulin and insulin-like growth factor 1 (IGF-1) signaling. |
| 1795 | 23292283 | Weak gene expression of insulin receptor (IR), IGF-1, insulin-like growth factor 1 receptor (IGF-1R), and insulin receptor substrate-1 (IRS-1) was observed in the diabetic BMSCs compared with normal BMSCs, together with decreased protein level of IGF-1, IGF-1R, IRS-1 and phosphorylated extracellular signal-regulated kinase. |
| 1796 | 23292283 | Therefore, impaired proliferation and osteogenic potential of BMSCs may be responsible for bone complications related to T1DM, mediated partially by impaired insulin and IGF-1 signaling. |
| 1797 | 23338941 | The IGF-1 receptor and regulation of nitric oxide bioavailability and insulin signalling in the endothelium. |
| 1798 | 23338941 | The insulin-like growth factor-1 receptor (IGF-1R), like the insulin receptor (IR), plays a significant role in determining bioavailability of the critical signalling molecule nitric oxide (NO) and hence, modulates endothelial cell function, particularly in response to stimulation with insulin. |
| 1799 | 23397157 | Insulin and insulin-like growth factor-1 (IGF-1) are important regulators of developmental and cognitive functions in the central nervous system. |
| 1800 | 23397157 | Aim of the present study was to examine the effects of maternal diabetes on insulin receptor (InsR) and IGF-1 receptor (IGF-1R) expression in the developing rat cerebellum. |
| 1801 | 23397157 | The expression of InsR and IGF-1R in cerebelli was evaluated using real-time PCR and western blot analysis. |
| 1802 | 23397157 | We found a significant upregulation of both IGF-1R and InsR transcripts in cerebellum of pups born to diabetic mothers at P0, compared to controls. |
| 1803 | 23397157 | In contrast to InsR, which does not show any difference, there was a markedly reduction in cerebellar expression of IGF-1R mRNA and protein level in the diabetic group of newborns at P7. |
| 1804 | 23397157 | Moreover, 2 weeks after birth, mRNA expression and protein levels of both InsR and IGF-1R in cerebellum of the diabetic group was significantly downregulated. |
| 1805 | 23397157 | Compared to controls, we did not find any difference in cerebellar InsR or IGF-1R mRNA and protein levels in the insulin treated group. |
| 1806 | 23397157 | The present study revealed that diabetes during pregnancy strongly influences the regulation of both InsR and IGF-1R in the developing cerebellum. |
| 1807 | 23397157 | Insulin and insulin-like growth factor-1 (IGF-1) are important regulators of developmental and cognitive functions in the central nervous system. |
| 1808 | 23397157 | Aim of the present study was to examine the effects of maternal diabetes on insulin receptor (InsR) and IGF-1 receptor (IGF-1R) expression in the developing rat cerebellum. |
| 1809 | 23397157 | The expression of InsR and IGF-1R in cerebelli was evaluated using real-time PCR and western blot analysis. |
| 1810 | 23397157 | We found a significant upregulation of both IGF-1R and InsR transcripts in cerebellum of pups born to diabetic mothers at P0, compared to controls. |
| 1811 | 23397157 | In contrast to InsR, which does not show any difference, there was a markedly reduction in cerebellar expression of IGF-1R mRNA and protein level in the diabetic group of newborns at P7. |
| 1812 | 23397157 | Moreover, 2 weeks after birth, mRNA expression and protein levels of both InsR and IGF-1R in cerebellum of the diabetic group was significantly downregulated. |
| 1813 | 23397157 | Compared to controls, we did not find any difference in cerebellar InsR or IGF-1R mRNA and protein levels in the insulin treated group. |
| 1814 | 23397157 | The present study revealed that diabetes during pregnancy strongly influences the regulation of both InsR and IGF-1R in the developing cerebellum. |
| 1815 | 23397157 | Insulin and insulin-like growth factor-1 (IGF-1) are important regulators of developmental and cognitive functions in the central nervous system. |
| 1816 | 23397157 | Aim of the present study was to examine the effects of maternal diabetes on insulin receptor (InsR) and IGF-1 receptor (IGF-1R) expression in the developing rat cerebellum. |
| 1817 | 23397157 | The expression of InsR and IGF-1R in cerebelli was evaluated using real-time PCR and western blot analysis. |
| 1818 | 23397157 | We found a significant upregulation of both IGF-1R and InsR transcripts in cerebellum of pups born to diabetic mothers at P0, compared to controls. |
| 1819 | 23397157 | In contrast to InsR, which does not show any difference, there was a markedly reduction in cerebellar expression of IGF-1R mRNA and protein level in the diabetic group of newborns at P7. |
| 1820 | 23397157 | Moreover, 2 weeks after birth, mRNA expression and protein levels of both InsR and IGF-1R in cerebellum of the diabetic group was significantly downregulated. |
| 1821 | 23397157 | Compared to controls, we did not find any difference in cerebellar InsR or IGF-1R mRNA and protein levels in the insulin treated group. |
| 1822 | 23397157 | The present study revealed that diabetes during pregnancy strongly influences the regulation of both InsR and IGF-1R in the developing cerebellum. |
| 1823 | 23397157 | Insulin and insulin-like growth factor-1 (IGF-1) are important regulators of developmental and cognitive functions in the central nervous system. |
| 1824 | 23397157 | Aim of the present study was to examine the effects of maternal diabetes on insulin receptor (InsR) and IGF-1 receptor (IGF-1R) expression in the developing rat cerebellum. |
| 1825 | 23397157 | The expression of InsR and IGF-1R in cerebelli was evaluated using real-time PCR and western blot analysis. |
| 1826 | 23397157 | We found a significant upregulation of both IGF-1R and InsR transcripts in cerebellum of pups born to diabetic mothers at P0, compared to controls. |
| 1827 | 23397157 | In contrast to InsR, which does not show any difference, there was a markedly reduction in cerebellar expression of IGF-1R mRNA and protein level in the diabetic group of newborns at P7. |
| 1828 | 23397157 | Moreover, 2 weeks after birth, mRNA expression and protein levels of both InsR and IGF-1R in cerebellum of the diabetic group was significantly downregulated. |
| 1829 | 23397157 | Compared to controls, we did not find any difference in cerebellar InsR or IGF-1R mRNA and protein levels in the insulin treated group. |
| 1830 | 23397157 | The present study revealed that diabetes during pregnancy strongly influences the regulation of both InsR and IGF-1R in the developing cerebellum. |
| 1831 | 23397157 | Insulin and insulin-like growth factor-1 (IGF-1) are important regulators of developmental and cognitive functions in the central nervous system. |
| 1832 | 23397157 | Aim of the present study was to examine the effects of maternal diabetes on insulin receptor (InsR) and IGF-1 receptor (IGF-1R) expression in the developing rat cerebellum. |
| 1833 | 23397157 | The expression of InsR and IGF-1R in cerebelli was evaluated using real-time PCR and western blot analysis. |
| 1834 | 23397157 | We found a significant upregulation of both IGF-1R and InsR transcripts in cerebellum of pups born to diabetic mothers at P0, compared to controls. |
| 1835 | 23397157 | In contrast to InsR, which does not show any difference, there was a markedly reduction in cerebellar expression of IGF-1R mRNA and protein level in the diabetic group of newborns at P7. |
| 1836 | 23397157 | Moreover, 2 weeks after birth, mRNA expression and protein levels of both InsR and IGF-1R in cerebellum of the diabetic group was significantly downregulated. |
| 1837 | 23397157 | Compared to controls, we did not find any difference in cerebellar InsR or IGF-1R mRNA and protein levels in the insulin treated group. |
| 1838 | 23397157 | The present study revealed that diabetes during pregnancy strongly influences the regulation of both InsR and IGF-1R in the developing cerebellum. |
| 1839 | 23397157 | Insulin and insulin-like growth factor-1 (IGF-1) are important regulators of developmental and cognitive functions in the central nervous system. |
| 1840 | 23397157 | Aim of the present study was to examine the effects of maternal diabetes on insulin receptor (InsR) and IGF-1 receptor (IGF-1R) expression in the developing rat cerebellum. |
| 1841 | 23397157 | The expression of InsR and IGF-1R in cerebelli was evaluated using real-time PCR and western blot analysis. |
| 1842 | 23397157 | We found a significant upregulation of both IGF-1R and InsR transcripts in cerebellum of pups born to diabetic mothers at P0, compared to controls. |
| 1843 | 23397157 | In contrast to InsR, which does not show any difference, there was a markedly reduction in cerebellar expression of IGF-1R mRNA and protein level in the diabetic group of newborns at P7. |
| 1844 | 23397157 | Moreover, 2 weeks after birth, mRNA expression and protein levels of both InsR and IGF-1R in cerebellum of the diabetic group was significantly downregulated. |
| 1845 | 23397157 | Compared to controls, we did not find any difference in cerebellar InsR or IGF-1R mRNA and protein levels in the insulin treated group. |
| 1846 | 23397157 | The present study revealed that diabetes during pregnancy strongly influences the regulation of both InsR and IGF-1R in the developing cerebellum. |
| 1847 | 23397157 | Insulin and insulin-like growth factor-1 (IGF-1) are important regulators of developmental and cognitive functions in the central nervous system. |
| 1848 | 23397157 | Aim of the present study was to examine the effects of maternal diabetes on insulin receptor (InsR) and IGF-1 receptor (IGF-1R) expression in the developing rat cerebellum. |
| 1849 | 23397157 | The expression of InsR and IGF-1R in cerebelli was evaluated using real-time PCR and western blot analysis. |
| 1850 | 23397157 | We found a significant upregulation of both IGF-1R and InsR transcripts in cerebellum of pups born to diabetic mothers at P0, compared to controls. |
| 1851 | 23397157 | In contrast to InsR, which does not show any difference, there was a markedly reduction in cerebellar expression of IGF-1R mRNA and protein level in the diabetic group of newborns at P7. |
| 1852 | 23397157 | Moreover, 2 weeks after birth, mRNA expression and protein levels of both InsR and IGF-1R in cerebellum of the diabetic group was significantly downregulated. |
| 1853 | 23397157 | Compared to controls, we did not find any difference in cerebellar InsR or IGF-1R mRNA and protein levels in the insulin treated group. |
| 1854 | 23397157 | The present study revealed that diabetes during pregnancy strongly influences the regulation of both InsR and IGF-1R in the developing cerebellum. |
| 1855 | 23472139 | Activation of Akt by advanced glycation end products (AGEs): involvement of IGF-1 receptor and caveolin-1. |
| 1856 | 23472139 | AGEs activate signaling proteins such as Src, Akt and ERK1/2. |
| 1857 | 23472139 | The AGEs-stimulated Akt activation was blocked by a PI3-kinase inhibitor LY 294002, Src inhibitor PP2, an antioxidant NAC, superoxide scavenger Tiron, or nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase inhibitor DPI, suggesting the involvement of Src and NAD(P)H oxidase in the activation of PI3-kinase-Akt pathway by AGEs. |
| 1858 | 23472139 | The AGEs-stimulated Akt activity was sensitive to Insulin-like growth factor 1 receptor (IGF-1R) kinase inhibitor AG1024. |
| 1859 | 23472139 | Furthermore, AGEs induced phosphorylation of IGF-1 receptorβsubunit (IGF-1Rβ) on Tyr1135/1136, which was sensitive to PP2, indicating that AGEs stimulate Akt activity by transactivating IGF-1 receptor. |
| 1860 | 23472139 | In addition, the AGEs-stimulated Akt activation was attenuated by β-methylcyclodextrin that abolishes the structure of caveolae, and by lowering caveolin-1 (Cav-1) levels with siRNAs. |
| 1861 | 23472139 | Furthermore, addition of AGEs enhanced the interaction of phospho-Cav-1 with IGF-1Rβ and transfection of 3T3-L1 cells with Cav-1 Y14F mutants inhibited the activation of Akt by AGEs. |
| 1862 | 23472139 | These results suggest that AGEs activate NAD(P)H oxidase and Src which in turn phosphorylates IGF-1 receptor and Cav-1 leading to activation of IGF-1 receptor and the downstream Akt in 3T3-L1 cells. |
| 1863 | 23472139 | AGEs treatment promoted the differentiation of 3T3-L1 preadipocytes and addition of AG1024, LY 294002 or Akt inhibitor attenuated the promoting effect of AGEs on adipogenesis, suggesting that IGF-1 receptor, PI3-Kinase and Akt are involved in the facilitation of adipogenesis by AGEs. |
| 1864 | 23493758 | However, therapies with monoclonal antibodies targeting the IGF1 receptor (IGF1R) have been largely unsuccessful. |
| 1865 | 23493758 | One of the potential reasons for this failure is the existence of the highly homologous insulin receptor (IR), which appears to be at least equally efficient as the IGF1R in the transition of mitogenic signals to the nucleus and promotion of cell growth. |
| 1866 | 23493758 | Furthermore, IGF1 and insulin receptors can form hybrid receptors sensitive to stimulation of all three ligands of the system: insulin, IGF1, and IGF2. |
| 1867 | 23493758 | Although the connection between insulin, diabetes, and cancer has been established for years now, clear evidence that demonstrate the redundancy of insulin and insulin receptors and insulin-like growth factors and their receptors in cancer is missing. |
| 1868 | 23493758 | However, therapies with monoclonal antibodies targeting the IGF1 receptor (IGF1R) have been largely unsuccessful. |
| 1869 | 23493758 | One of the potential reasons for this failure is the existence of the highly homologous insulin receptor (IR), which appears to be at least equally efficient as the IGF1R in the transition of mitogenic signals to the nucleus and promotion of cell growth. |
| 1870 | 23493758 | Furthermore, IGF1 and insulin receptors can form hybrid receptors sensitive to stimulation of all three ligands of the system: insulin, IGF1, and IGF2. |
| 1871 | 23493758 | Although the connection between insulin, diabetes, and cancer has been established for years now, clear evidence that demonstrate the redundancy of insulin and insulin receptors and insulin-like growth factors and their receptors in cancer is missing. |
| 1872 | 23507573 | Minireview: nuclear insulin and insulin-like growth factor-1 receptors: a novel paradigm in signal transduction. |
| 1873 | 23507573 | The specificity of the insulin receptor (InsR) and insulin-like growth factor-1 receptor (IGF1R) signaling pathways has been the focus of significant debate over the past few years. |
| 1874 | 23507573 | Recent evidence showing nuclear import and a direct transcriptional role for both InsR and IGF1R adds a new layer of complexity to this dialog. |
| 1875 | 23507573 | Hence, in addition to the classical roles associated with cell-surface receptors (eg, ligand binding, autophosphorylation of the tyrosine kinase domain, activation of insulin receptor substrate 1 (IRS-1) and additional substrates, protein-protein interactions with membrane and cytoplasm components), new data are consistent with nuclear (genomic) role(s) for both InsR and IGF1R. |
| 1876 | 23507573 | The present review provides a brief overview of the physical and functional similarities and differences between InsR and IGF1R and describes data from a number of laboratories providing evidence for a new layer of signaling regulation (ie, the ability of InsR and IGF1R to translocate to the cell nucleus and to elicit genomic activities usually associated with transcription factors). |
| 1877 | 23507573 | The ability of InsR and IGF1R to function as transcription factors, although poorly understood, constitutes a new paradigm in signal transduction. |
| 1878 | 23507573 | Although research on the role of nuclear InsR/IGF1R is still in its infancy, we believe that this rapidly developing area may have a major basic and translational impact on the fields of metabolism, diabetes, and cancer. |
| 1879 | 23507573 | Minireview: nuclear insulin and insulin-like growth factor-1 receptors: a novel paradigm in signal transduction. |
| 1880 | 23507573 | The specificity of the insulin receptor (InsR) and insulin-like growth factor-1 receptor (IGF1R) signaling pathways has been the focus of significant debate over the past few years. |
| 1881 | 23507573 | Recent evidence showing nuclear import and a direct transcriptional role for both InsR and IGF1R adds a new layer of complexity to this dialog. |
| 1882 | 23507573 | Hence, in addition to the classical roles associated with cell-surface receptors (eg, ligand binding, autophosphorylation of the tyrosine kinase domain, activation of insulin receptor substrate 1 (IRS-1) and additional substrates, protein-protein interactions with membrane and cytoplasm components), new data are consistent with nuclear (genomic) role(s) for both InsR and IGF1R. |
| 1883 | 23507573 | The present review provides a brief overview of the physical and functional similarities and differences between InsR and IGF1R and describes data from a number of laboratories providing evidence for a new layer of signaling regulation (ie, the ability of InsR and IGF1R to translocate to the cell nucleus and to elicit genomic activities usually associated with transcription factors). |
| 1884 | 23507573 | The ability of InsR and IGF1R to function as transcription factors, although poorly understood, constitutes a new paradigm in signal transduction. |
| 1885 | 23507573 | Although research on the role of nuclear InsR/IGF1R is still in its infancy, we believe that this rapidly developing area may have a major basic and translational impact on the fields of metabolism, diabetes, and cancer. |
| 1886 | 23507573 | Minireview: nuclear insulin and insulin-like growth factor-1 receptors: a novel paradigm in signal transduction. |
| 1887 | 23507573 | The specificity of the insulin receptor (InsR) and insulin-like growth factor-1 receptor (IGF1R) signaling pathways has been the focus of significant debate over the past few years. |
| 1888 | 23507573 | Recent evidence showing nuclear import and a direct transcriptional role for both InsR and IGF1R adds a new layer of complexity to this dialog. |
| 1889 | 23507573 | Hence, in addition to the classical roles associated with cell-surface receptors (eg, ligand binding, autophosphorylation of the tyrosine kinase domain, activation of insulin receptor substrate 1 (IRS-1) and additional substrates, protein-protein interactions with membrane and cytoplasm components), new data are consistent with nuclear (genomic) role(s) for both InsR and IGF1R. |
| 1890 | 23507573 | The present review provides a brief overview of the physical and functional similarities and differences between InsR and IGF1R and describes data from a number of laboratories providing evidence for a new layer of signaling regulation (ie, the ability of InsR and IGF1R to translocate to the cell nucleus and to elicit genomic activities usually associated with transcription factors). |
| 1891 | 23507573 | The ability of InsR and IGF1R to function as transcription factors, although poorly understood, constitutes a new paradigm in signal transduction. |
| 1892 | 23507573 | Although research on the role of nuclear InsR/IGF1R is still in its infancy, we believe that this rapidly developing area may have a major basic and translational impact on the fields of metabolism, diabetes, and cancer. |
| 1893 | 23507573 | Minireview: nuclear insulin and insulin-like growth factor-1 receptors: a novel paradigm in signal transduction. |
| 1894 | 23507573 | The specificity of the insulin receptor (InsR) and insulin-like growth factor-1 receptor (IGF1R) signaling pathways has been the focus of significant debate over the past few years. |
| 1895 | 23507573 | Recent evidence showing nuclear import and a direct transcriptional role for both InsR and IGF1R adds a new layer of complexity to this dialog. |
| 1896 | 23507573 | Hence, in addition to the classical roles associated with cell-surface receptors (eg, ligand binding, autophosphorylation of the tyrosine kinase domain, activation of insulin receptor substrate 1 (IRS-1) and additional substrates, protein-protein interactions with membrane and cytoplasm components), new data are consistent with nuclear (genomic) role(s) for both InsR and IGF1R. |
| 1897 | 23507573 | The present review provides a brief overview of the physical and functional similarities and differences between InsR and IGF1R and describes data from a number of laboratories providing evidence for a new layer of signaling regulation (ie, the ability of InsR and IGF1R to translocate to the cell nucleus and to elicit genomic activities usually associated with transcription factors). |
| 1898 | 23507573 | The ability of InsR and IGF1R to function as transcription factors, although poorly understood, constitutes a new paradigm in signal transduction. |
| 1899 | 23507573 | Although research on the role of nuclear InsR/IGF1R is still in its infancy, we believe that this rapidly developing area may have a major basic and translational impact on the fields of metabolism, diabetes, and cancer. |
| 1900 | 23507573 | Minireview: nuclear insulin and insulin-like growth factor-1 receptors: a novel paradigm in signal transduction. |
| 1901 | 23507573 | The specificity of the insulin receptor (InsR) and insulin-like growth factor-1 receptor (IGF1R) signaling pathways has been the focus of significant debate over the past few years. |
| 1902 | 23507573 | Recent evidence showing nuclear import and a direct transcriptional role for both InsR and IGF1R adds a new layer of complexity to this dialog. |
| 1903 | 23507573 | Hence, in addition to the classical roles associated with cell-surface receptors (eg, ligand binding, autophosphorylation of the tyrosine kinase domain, activation of insulin receptor substrate 1 (IRS-1) and additional substrates, protein-protein interactions with membrane and cytoplasm components), new data are consistent with nuclear (genomic) role(s) for both InsR and IGF1R. |
| 1904 | 23507573 | The present review provides a brief overview of the physical and functional similarities and differences between InsR and IGF1R and describes data from a number of laboratories providing evidence for a new layer of signaling regulation (ie, the ability of InsR and IGF1R to translocate to the cell nucleus and to elicit genomic activities usually associated with transcription factors). |
| 1905 | 23507573 | The ability of InsR and IGF1R to function as transcription factors, although poorly understood, constitutes a new paradigm in signal transduction. |
| 1906 | 23507573 | Although research on the role of nuclear InsR/IGF1R is still in its infancy, we believe that this rapidly developing area may have a major basic and translational impact on the fields of metabolism, diabetes, and cancer. |
| 1907 | 23507573 | Minireview: nuclear insulin and insulin-like growth factor-1 receptors: a novel paradigm in signal transduction. |
| 1908 | 23507573 | The specificity of the insulin receptor (InsR) and insulin-like growth factor-1 receptor (IGF1R) signaling pathways has been the focus of significant debate over the past few years. |
| 1909 | 23507573 | Recent evidence showing nuclear import and a direct transcriptional role for both InsR and IGF1R adds a new layer of complexity to this dialog. |
| 1910 | 23507573 | Hence, in addition to the classical roles associated with cell-surface receptors (eg, ligand binding, autophosphorylation of the tyrosine kinase domain, activation of insulin receptor substrate 1 (IRS-1) and additional substrates, protein-protein interactions with membrane and cytoplasm components), new data are consistent with nuclear (genomic) role(s) for both InsR and IGF1R. |
| 1911 | 23507573 | The present review provides a brief overview of the physical and functional similarities and differences between InsR and IGF1R and describes data from a number of laboratories providing evidence for a new layer of signaling regulation (ie, the ability of InsR and IGF1R to translocate to the cell nucleus and to elicit genomic activities usually associated with transcription factors). |
| 1912 | 23507573 | The ability of InsR and IGF1R to function as transcription factors, although poorly understood, constitutes a new paradigm in signal transduction. |
| 1913 | 23507573 | Although research on the role of nuclear InsR/IGF1R is still in its infancy, we believe that this rapidly developing area may have a major basic and translational impact on the fields of metabolism, diabetes, and cancer. |
| 1914 | 23515289 | Recently it was demonstrated that both the insulin receptor (IR) and the IGF-IR mediate hyperinsulinemia's mitogenic effect in several breast cancer models. |
| 1915 | 23537438 | Insulin-like growth-factor-1-induced PKB signaling and Egr-1 expression is inhibited by curcumin in A-10 vascular smooth muscle cells. |
| 1916 | 23537438 | Insulin-like growth factor 1 (IGF-1) is a mitogenic factor that stimulates the signaling pathways responsible for inducing hypertrophic and proliferative responses in vascular smooth muscle cells (VSMC). |
| 1917 | 23537438 | We have previously demonstrated that IGF-1 receptor (IGF-1R) plays a key role in transducing the hypertrophic and proliferative responses of angiotensin II (Ang-II) and endothelin-1 (ET-1). |
| 1918 | 23537438 | In this study, we determined the effect of curcumin on IGF-1-induced phosphorylation of protein kinase B (PKB), glycogen synthase kinase-3β (GSK-3β), and IGF-1R in VSMC. |
| 1919 | 23537438 | Curcumin inhibited IGF-1-induced phosphorylation of PKB and GSK-3β as well as the IGF-1R β subunit in a dose-dependent fashion. |
| 1920 | 23537438 | Insulin-like growth-factor-1-induced PKB signaling and Egr-1 expression is inhibited by curcumin in A-10 vascular smooth muscle cells. |
| 1921 | 23537438 | Insulin-like growth factor 1 (IGF-1) is a mitogenic factor that stimulates the signaling pathways responsible for inducing hypertrophic and proliferative responses in vascular smooth muscle cells (VSMC). |
| 1922 | 23537438 | We have previously demonstrated that IGF-1 receptor (IGF-1R) plays a key role in transducing the hypertrophic and proliferative responses of angiotensin II (Ang-II) and endothelin-1 (ET-1). |
| 1923 | 23537438 | In this study, we determined the effect of curcumin on IGF-1-induced phosphorylation of protein kinase B (PKB), glycogen synthase kinase-3β (GSK-3β), and IGF-1R in VSMC. |
| 1924 | 23537438 | Curcumin inhibited IGF-1-induced phosphorylation of PKB and GSK-3β as well as the IGF-1R β subunit in a dose-dependent fashion. |
| 1925 | 23537438 | Insulin-like growth-factor-1-induced PKB signaling and Egr-1 expression is inhibited by curcumin in A-10 vascular smooth muscle cells. |
| 1926 | 23537438 | Insulin-like growth factor 1 (IGF-1) is a mitogenic factor that stimulates the signaling pathways responsible for inducing hypertrophic and proliferative responses in vascular smooth muscle cells (VSMC). |
| 1927 | 23537438 | We have previously demonstrated that IGF-1 receptor (IGF-1R) plays a key role in transducing the hypertrophic and proliferative responses of angiotensin II (Ang-II) and endothelin-1 (ET-1). |
| 1928 | 23537438 | In this study, we determined the effect of curcumin on IGF-1-induced phosphorylation of protein kinase B (PKB), glycogen synthase kinase-3β (GSK-3β), and IGF-1R in VSMC. |
| 1929 | 23537438 | Curcumin inhibited IGF-1-induced phosphorylation of PKB and GSK-3β as well as the IGF-1R β subunit in a dose-dependent fashion. |
| 1930 | 23538787 | Vesiculin, a novel IGF-II-like protein was recently isolated from the secretory granules of murine β-cells, and preliminary studies indicate it is capable of signalling via the insulin receptor (IR)/insulin-like growth factor receptor 1(IGF1R) family giving it the potential to elicit both metabolic and mitogenic responses in the beta-cell. |
| 1931 | 23572162 | Here, we use a mouse model of Her2-mediated breast cancer on a background of hyperinsulinemia to determine how elevated circulating insulin levels affect Her2-mediated primary tumor growth and lung metastasis. |
| 1932 | 23572162 | In tumor tissues removed at 2, 4, and 6 weeks of Neu-NT overexpression, we observed increased tumor mass and higher phosphorylation of the insulin receptor/IGF1 receptor, suggesting that activation of these receptors in conditions of hyperinsulinemia could contribute to the increased growth of mammary tumors. |
| 1933 | 23579096 | Amadori products promote cellular senescence activating insulin-like growth factor-1 receptor and down-regulating the antioxidant enzyme catalase. |
| 1934 | 23579096 | We treated cultured human mesangial cells with glycated albumin, one of the most abundant Amadori product, and senescence was assessed by determining the senescence associated β-galactosidase activity and the expression of the cell cycle regulators p53 and p21. |
| 1935 | 23579096 | We demonstrated that prolonged exposition (more than 24h) to glycated albumin induced senescence and, in parallel, incremented the release of IGF-1 and the activation of the IGF-1 receptor. |
| 1936 | 23579096 | Activation of IGF-1R, after GA addition, promoted a reduction in the catalase content through the constitutive activation of Ras and erk1/2 proteins which were, in turn, responsible of the observed GA-induced senescence. |
| 1937 | 23579096 | In conclusion, we propose that the Amadori product, glycated albumin, promotes premature cell senescence in mesangial cells through the activation of the IGF-1 receptor and the subsequent reduction in the antioxidant enzyme catalase. |
| 1938 | 23579096 | Amadori products promote cellular senescence activating insulin-like growth factor-1 receptor and down-regulating the antioxidant enzyme catalase. |
| 1939 | 23579096 | We treated cultured human mesangial cells with glycated albumin, one of the most abundant Amadori product, and senescence was assessed by determining the senescence associated β-galactosidase activity and the expression of the cell cycle regulators p53 and p21. |
| 1940 | 23579096 | We demonstrated that prolonged exposition (more than 24h) to glycated albumin induced senescence and, in parallel, incremented the release of IGF-1 and the activation of the IGF-1 receptor. |
| 1941 | 23579096 | Activation of IGF-1R, after GA addition, promoted a reduction in the catalase content through the constitutive activation of Ras and erk1/2 proteins which were, in turn, responsible of the observed GA-induced senescence. |
| 1942 | 23579096 | In conclusion, we propose that the Amadori product, glycated albumin, promotes premature cell senescence in mesangial cells through the activation of the IGF-1 receptor and the subsequent reduction in the antioxidant enzyme catalase. |
| 1943 | 23614367 | Growth factor receptor-bound protein 10-mediated negative regulation of the insulin-like growth factor-1 receptor-activated signalling pathway results in cognitive disorder in diabetic rats. |
| 1944 | 23614367 | Growth factor receptor-bound protein 10 (Grb10) is a Src homology 2 domain-containing protein and one of the binding partners for several transmembrane tyrosine kinase receptors, including insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF1-R). |
| 1945 | 23614367 | Growth factor receptor-bound protein 10-mediated negative regulation of the insulin-like growth factor-1 receptor-activated signalling pathway results in cognitive disorder in diabetic rats. |
| 1946 | 23614367 | Growth factor receptor-bound protein 10 (Grb10) is a Src homology 2 domain-containing protein and one of the binding partners for several transmembrane tyrosine kinase receptors, including insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF1-R). |
| 1947 | 23620761 | Metformin downregulates the insulin/IGF-I signaling pathway and inhibits different uterine serous carcinoma (USC) cells proliferation and migration in p53-dependent or -independent manners. |
| 1948 | 23620761 | The insulin-like growth factors (IGFs) play a prominent role in cancer biology and their mechanisms of action are tightly interconnected with the insulin signaling pathways. |
| 1949 | 23620761 | Given the cross-talk between the insulin and IGF signaling pathways, the aim of this study was to examine the hypothesis that the anti-proliferative actions of metformin in uterine serous carcinoma (USC) are potentially mediated via suppression of the IGF-I receptor (IGF-IR) pathway. |
| 1950 | 23677929 | Implication of insulin receptor A isoform and IRA/IGF-IR hybrid receptors in the aortic vascular smooth muscle cell proliferation: role of TNF-α and IGF-II. |
| 1951 | 23677929 | Moreover, insulin, through ERK signaling, and the proatherogenic stimuli, through ERK and p38 signaling, induced a higher proliferation in IRA than IRB VSMCs. |
| 1952 | 23677929 | The latter effect might be due to IRA cells showing a higher expression of angiotensin II, endothelin 1, and thromboxane 2 receptors and basal association between IRA and these receptors. |
| 1953 | 23677929 | More importantly, we observed a significant increase of IRA, TNF-R1, and IGF-IR expression as well as higher association of IRA with TNF-R1 or IGF-IR in the aorta from ApoE(-/-) and BATIRKO mice, 2 models showing vascular damage. |
| 1954 | 23677929 | Finally, our data suggest that the IRA isoform and its association with TNF-R1 or IGF-IR confers proliferative advantage to VSMCs, mainly in response to TNF-α or IGF-II, which might be of significance in the early atherosclerotic process. |
| 1955 | 23677929 | Implication of insulin receptor A isoform and IRA/IGF-IR hybrid receptors in the aortic vascular smooth muscle cell proliferation: role of TNF-α and IGF-II. |
| 1956 | 23677929 | Moreover, insulin, through ERK signaling, and the proatherogenic stimuli, through ERK and p38 signaling, induced a higher proliferation in IRA than IRB VSMCs. |
| 1957 | 23677929 | The latter effect might be due to IRA cells showing a higher expression of angiotensin II, endothelin 1, and thromboxane 2 receptors and basal association between IRA and these receptors. |
| 1958 | 23677929 | More importantly, we observed a significant increase of IRA, TNF-R1, and IGF-IR expression as well as higher association of IRA with TNF-R1 or IGF-IR in the aorta from ApoE(-/-) and BATIRKO mice, 2 models showing vascular damage. |
| 1959 | 23677929 | Finally, our data suggest that the IRA isoform and its association with TNF-R1 or IGF-IR confers proliferative advantage to VSMCs, mainly in response to TNF-α or IGF-II, which might be of significance in the early atherosclerotic process. |
| 1960 | 23735664 | The Zn supplement prevented a decrease in the activity and mRNA of alkaline phosphatase (ALP), osteocalcin mRNA, and hydroxyproline and calcium levels, and an increase in the activity and mRNA of tartrate-resistant acid phosphatase (TRAP) and cathepsin K in the proximal tibia of diabetic rats. |
| 1961 | 23735664 | The increase in mRNA levels of receptor for activation of NF-κB (RANK), c-fos, c-jun, TRAP, and cathepsin K and decrease in the expression of Runx2, Dlx5, osterix, ALP, osteocalcin, and collagen were prevented by the supplement. |
| 1962 | 23735664 | The decrease in β-catenin, phosphorylated GSK3β, phosphorylated Akt, insulin-like growth factor 1 (IGF-1), and IGF-1 receptor (IGF-1R) protein levels in diabetic rats was also inhibited, although Zn did not affect the diabetes-increased gene and protein expression of Sost and Dkk1. |
| 1963 | 23735664 | These results suggested that Zn prevented the diabetes-induced increase in osteoclastogenesis and decrease in osteoblastogenesis by inhibiting RANK expression and stimulating IGF-1/IGF-1R/Akt/GSK3β/β-catenin signaling, respectively. |
| 1964 | 23735664 | The Zn supplement prevented a decrease in the activity and mRNA of alkaline phosphatase (ALP), osteocalcin mRNA, and hydroxyproline and calcium levels, and an increase in the activity and mRNA of tartrate-resistant acid phosphatase (TRAP) and cathepsin K in the proximal tibia of diabetic rats. |
| 1965 | 23735664 | The increase in mRNA levels of receptor for activation of NF-κB (RANK), c-fos, c-jun, TRAP, and cathepsin K and decrease in the expression of Runx2, Dlx5, osterix, ALP, osteocalcin, and collagen were prevented by the supplement. |
| 1966 | 23735664 | The decrease in β-catenin, phosphorylated GSK3β, phosphorylated Akt, insulin-like growth factor 1 (IGF-1), and IGF-1 receptor (IGF-1R) protein levels in diabetic rats was also inhibited, although Zn did not affect the diabetes-increased gene and protein expression of Sost and Dkk1. |
| 1967 | 23735664 | These results suggested that Zn prevented the diabetes-induced increase in osteoclastogenesis and decrease in osteoblastogenesis by inhibiting RANK expression and stimulating IGF-1/IGF-1R/Akt/GSK3β/β-catenin signaling, respectively. |
| 1968 | 23736539 | In IGF-IR(+/-) mice, both growth and expression of myogenic genes (MyoD and myogenin; markers of satellite cell proliferation and differentiation, respectively) were depressed. |
| 1969 | 23736539 | Likewise, in injured muscles of IGF-IR(+/-) mice, there was impaired regeneration, depressed expression of MyoD and myogenin, and increased expression of TGF-β1, α-SMA, collagen I, and fibrosis. |
| 1970 | 23736539 | In C2C12 myoblasts (a model of satellite cells), IGF-I treatment inhibited TGF-β1-stimulated Smad3 phosphorylation, its nuclear translocation, and expression of fibronectin. |
| 1971 | 23736539 | Using immunoprecipitation assay, we found an interaction between p-Akt or Akt with Smad3 in wild-type mouse muscles and in C2C12 myoblasts; importantly, IGF-I increased p-Akt and Smad3 interaction, whereas TGF-β1 decreased it. |
| 1972 | 23736539 | Therefore, in muscles of IGF-IR(+/-) mice, the reduction in IGF-IR reduces p-Akt, allowing for dissociation and nuclear translocation of Smad3 to enhance the TGF-β1 signaling pathway, leading to fibrosis. |
| 1973 | 23736539 | In IGF-IR(+/-) mice, both growth and expression of myogenic genes (MyoD and myogenin; markers of satellite cell proliferation and differentiation, respectively) were depressed. |
| 1974 | 23736539 | Likewise, in injured muscles of IGF-IR(+/-) mice, there was impaired regeneration, depressed expression of MyoD and myogenin, and increased expression of TGF-β1, α-SMA, collagen I, and fibrosis. |
| 1975 | 23736539 | In C2C12 myoblasts (a model of satellite cells), IGF-I treatment inhibited TGF-β1-stimulated Smad3 phosphorylation, its nuclear translocation, and expression of fibronectin. |
| 1976 | 23736539 | Using immunoprecipitation assay, we found an interaction between p-Akt or Akt with Smad3 in wild-type mouse muscles and in C2C12 myoblasts; importantly, IGF-I increased p-Akt and Smad3 interaction, whereas TGF-β1 decreased it. |
| 1977 | 23736539 | Therefore, in muscles of IGF-IR(+/-) mice, the reduction in IGF-IR reduces p-Akt, allowing for dissociation and nuclear translocation of Smad3 to enhance the TGF-β1 signaling pathway, leading to fibrosis. |
| 1978 | 23736539 | In IGF-IR(+/-) mice, both growth and expression of myogenic genes (MyoD and myogenin; markers of satellite cell proliferation and differentiation, respectively) were depressed. |
| 1979 | 23736539 | Likewise, in injured muscles of IGF-IR(+/-) mice, there was impaired regeneration, depressed expression of MyoD and myogenin, and increased expression of TGF-β1, α-SMA, collagen I, and fibrosis. |
| 1980 | 23736539 | In C2C12 myoblasts (a model of satellite cells), IGF-I treatment inhibited TGF-β1-stimulated Smad3 phosphorylation, its nuclear translocation, and expression of fibronectin. |
| 1981 | 23736539 | Using immunoprecipitation assay, we found an interaction between p-Akt or Akt with Smad3 in wild-type mouse muscles and in C2C12 myoblasts; importantly, IGF-I increased p-Akt and Smad3 interaction, whereas TGF-β1 decreased it. |
| 1982 | 23736539 | Therefore, in muscles of IGF-IR(+/-) mice, the reduction in IGF-IR reduces p-Akt, allowing for dissociation and nuclear translocation of Smad3 to enhance the TGF-β1 signaling pathway, leading to fibrosis. |
| 1983 | 23835331 | Insulin receptor phosphorylation by endogenous insulin or the insulin analog AspB10 promotes mammary tumor growth independent of the IGF-I receptor. |
| 1984 | 23835331 | Endogenous hyperinsulinemia and insulin receptor (IR)/IGF-I receptor (IGF-IR) phosphorylation in tumors are associated with a worse prognosis in women with breast cancer. |
| 1985 | 23835331 | We aimed to determine whether stimulating the IR with the insulin analog AspB10 could increase tumor growth independently of IGF-IR signaling. |
| 1986 | 23835331 | We induced orthotopic mammary tumors in control FVB/n and hyperinsulinemic MKR mice, and treated them with the insulin analog AspB10, recombinant human IGF-I, or vehicle. |
| 1987 | 23835331 | IGF-I led to activation of both the IGF-IR and IR and probably hybrid receptors. |
| 1988 | 23835331 | Insulin receptor phosphorylation by endogenous insulin or the insulin analog AspB10 promotes mammary tumor growth independent of the IGF-I receptor. |
| 1989 | 23835331 | Endogenous hyperinsulinemia and insulin receptor (IR)/IGF-I receptor (IGF-IR) phosphorylation in tumors are associated with a worse prognosis in women with breast cancer. |
| 1990 | 23835331 | We aimed to determine whether stimulating the IR with the insulin analog AspB10 could increase tumor growth independently of IGF-IR signaling. |
| 1991 | 23835331 | We induced orthotopic mammary tumors in control FVB/n and hyperinsulinemic MKR mice, and treated them with the insulin analog AspB10, recombinant human IGF-I, or vehicle. |
| 1992 | 23835331 | IGF-I led to activation of both the IGF-IR and IR and probably hybrid receptors. |
| 1993 | 23835331 | Insulin receptor phosphorylation by endogenous insulin or the insulin analog AspB10 promotes mammary tumor growth independent of the IGF-I receptor. |
| 1994 | 23835331 | Endogenous hyperinsulinemia and insulin receptor (IR)/IGF-I receptor (IGF-IR) phosphorylation in tumors are associated with a worse prognosis in women with breast cancer. |
| 1995 | 23835331 | We aimed to determine whether stimulating the IR with the insulin analog AspB10 could increase tumor growth independently of IGF-IR signaling. |
| 1996 | 23835331 | We induced orthotopic mammary tumors in control FVB/n and hyperinsulinemic MKR mice, and treated them with the insulin analog AspB10, recombinant human IGF-I, or vehicle. |
| 1997 | 23835331 | IGF-I led to activation of both the IGF-IR and IR and probably hybrid receptors. |
| 1998 | 23861377 | In this study, we investigated whether loss of GH receptor (GHR) signaling in postnatal skeletal muscle alters muscle mass and regenerative ability in adult mice and whether this was dependent on IGF-1 receptor (IGF-1R) signaling. |
| 1999 | 23861377 | To do so, we used mouse models with skeletal muscle-specific loss of GHR signaling (mGHRKO), IGF-1R and insulin receptor signaling (MKR), or both GHR and IGF-1R/insulin receptor signaling (mGHRKO/MKR). |
| 2000 | 23861377 | Additionally, in our model, muscle Igf-1 expression is not dependent on GHR signaling in postnatal skeletal muscle. |
| 2001 | 23861377 | In this study, we investigated whether loss of GH receptor (GHR) signaling in postnatal skeletal muscle alters muscle mass and regenerative ability in adult mice and whether this was dependent on IGF-1 receptor (IGF-1R) signaling. |
| 2002 | 23861377 | To do so, we used mouse models with skeletal muscle-specific loss of GHR signaling (mGHRKO), IGF-1R and insulin receptor signaling (MKR), or both GHR and IGF-1R/insulin receptor signaling (mGHRKO/MKR). |
| 2003 | 23861377 | Additionally, in our model, muscle Igf-1 expression is not dependent on GHR signaling in postnatal skeletal muscle. |
| 2004 | 23900776 | Antibodies to TSHR and IGF-1R were present in animals challenged with hTSHR A-subunit plasmid, with predominantly TSH blocking antibodies and were profoundly hypothyroid. |
| 2005 | 24004957 | We discuss the contribution of the key factors of the pathway such as Calcineurin, IGF1 receptor, Akt kinase and HnRNPA2 in the propagation of signaling and their role in modulating genetic and epigenetic changes favoring cellular reprogramming towards tumorigenesis. |