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Gene Information
Gene symbol: G6PC
Gene name: glucose-6-phosphatase, catalytic subunit
HGNC ID: 4056
Synonyms: GSD1a
Related Genes
| # | Gene Symbol | Number of hits |
| 1 | ABCB11 | 1 hits |
| 2 | APLP2 | 1 hits |
| 3 | CARHSP1 | 1 hits |
| 4 | CCR2 | 1 hits |
| 5 | CD4 | 1 hits |
| 6 | CD8A | 1 hits |
| 7 | CHGA | 1 hits |
| 8 | CNBP | 1 hits |
| 9 | CPE | 1 hits |
| 10 | CREB1 | 1 hits |
| 11 | CREBBP | 1 hits |
| 12 | CTGF | 1 hits |
| 13 | CTLA4 | 1 hits |
| 14 | FASN | 1 hits |
| 15 | FOXA2 | 1 hits |
| 16 | FOXO1 | 1 hits |
| 17 | G6PC2 | 1 hits |
| 18 | G6PC3 | 1 hits |
| 19 | GAD1 | 1 hits |
| 20 | GAD2 | 1 hits |
| 21 | GFAP | 1 hits |
| 22 | GSR | 1 hits |
| 23 | H6PD | 1 hits |
| 24 | HFE | 1 hits |
| 25 | HIF1A | 1 hits |
| 26 | HLA-A | 1 hits |
| 27 | HNF4A | 1 hits |
| 28 | HSPD1 | 1 hits |
| 29 | IAPP | 1 hits |
| 30 | IFNG | 1 hits |
| 31 | IGFBP1 | 1 hits |
| 32 | INS | 1 hits |
| 33 | INSR | 1 hits |
| 34 | MAFA | 1 hits |
| 35 | MICB | 1 hits |
| 36 | PAX6 | 1 hits |
| 37 | PCK1 | 1 hits |
| 38 | PCK2 | 1 hits |
| 39 | PDX1 | 1 hits |
| 40 | PHOX2B | 1 hits |
| 41 | PPARG | 1 hits |
| 42 | PPARGC1A | 1 hits |
| 43 | PTPRN | 1 hits |
| 44 | PTPRN2 | 1 hits |
| 45 | RNF128 | 1 hits |
| 46 | SCN5A | 1 hits |
| 47 | SETD2 | 1 hits |
| 48 | SLC37A4 | 1 hits |
| 49 | SPAG8 | 1 hits |
| 50 | SREBF1 | 1 hits |
| 51 | TLR4 | 1 hits |
Related Sentences
| # | PMID | Sentence |
| 1 | 284505 | The behaviour of uricaemia and purine metabolism in the glycogen storage disease type I, in the glutathione reductase variant, after ethanol ingestion, after fructose load, the levels of lipoproteins and triglycerides in gouty patients and the reason for their increase, have been taken into special consideration. |
| 2 | 2160832 | Hormonal responses of glucose-6-phosphatase catalytic unit studied by stopped-flow analysis. |
| 3 | 2160832 | To obtain insight regarding the mechanism(s) of response of the catalytic unit of glucose-6-phosphatase (D-glucose-6-P phosphohydrolase; EC 3.1.3.9) to glucocorticoid administration and insulin deprivation, the functional enzyme concentration E0 was estimated from presteady-state kinetics by the stopped-flow technique. |
| 4 | 2160832 | These results showed that insulin deprivation resulted in an increased formation of fully active glucose-6-phosphatase catalytic unit. |
| 5 | 2160832 | It was concluded that glucocorticoid administration may promote formation of catalytic units of glucose-6-phosphatase which are less active than the enzyme normally present or formed in response to insulin deprivation. |
| 6 | 2160832 | Hormonal responses of glucose-6-phosphatase catalytic unit studied by stopped-flow analysis. |
| 7 | 2160832 | To obtain insight regarding the mechanism(s) of response of the catalytic unit of glucose-6-phosphatase (D-glucose-6-P phosphohydrolase; EC 3.1.3.9) to glucocorticoid administration and insulin deprivation, the functional enzyme concentration E0 was estimated from presteady-state kinetics by the stopped-flow technique. |
| 8 | 2160832 | These results showed that insulin deprivation resulted in an increased formation of fully active glucose-6-phosphatase catalytic unit. |
| 9 | 2160832 | It was concluded that glucocorticoid administration may promote formation of catalytic units of glucose-6-phosphatase which are less active than the enzyme normally present or formed in response to insulin deprivation. |
| 10 | 8574017 | Abnormally low hepatic glucose-6-phosphatase activity is found in human genetic deficiencies i.e. glycogen storage disease type I and in cases of developmental delay, found predominantly in preterm infants. |
| 11 | 8865366 | Expression and distribution of glucose-6-phosphatase catalytic subunit messenger RNA and its changes in the diabetic state. |
| 12 | 9341134 | Metabolic impact of adenovirus-mediated overexpression of the glucose-6-phosphatase catalytic subunit in hepatocytes. |
| 13 | 9689059 | Hepatocyte nuclear factor-1 acts as an accessory factor to enhance the inhibitory action of insulin on mouse glucose-6-phosphatase gene transcription. |
| 14 | 9689059 | Transcription of the gene encoding the glucose-6-phosphatase catalytic subunit (G6Pase) is stimulated by cAMP and glucocorticoids whereas insulin strongly inhibits both this induction and basal G6Pase gene transcription. |
| 15 | 9813078 | Perturbation of fuel homeostasis caused by overexpression of the glucose-6-phosphatase catalytic subunit in liver of normal rats. |
| 16 | 10078553 | Molecular cloning of a pancreatic islet-specific glucose-6-phosphatase catalytic subunit-related protein. |
| 17 | 10078553 | A pancreatic islet-specific glucose-6-phosphatase-related protein (IGRP) was cloned using a subtractive cDNA expression cloning procedure from mouse insulinoma tissue. |
| 18 | 10078553 | Whereas the liver glucose-6-phosphatase showed activity in these transfection systems, the IGRP failed to show glucose phosphotransferase or phosphatase activity with p-nitrophenol phosphate, inorganic pyrophosphate, or a range of sugar phosphates hydrolyzed by the liver enzyme. |
| 19 | 10078554 | Structure and promoter activity of an islet-specific glucose-6-phosphatase catalytic subunit-related gene. |
| 20 | 10078554 | Arden and associates have described the cloning of a novel cDNA that encodes an islet-specific G-6-Pase catalytic subunit-related protein (IGRP) (Arden SD, Zahn T, Steegers S, Webb S, Bergman B, O'Brien RM, Hutton JC: Molecular cloning of a pancreatic islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP). |
| 21 | 10078554 | Structure and promoter activity of an islet-specific glucose-6-phosphatase catalytic subunit-related gene. |
| 22 | 10078554 | Arden and associates have described the cloning of a novel cDNA that encodes an islet-specific G-6-Pase catalytic subunit-related protein (IGRP) (Arden SD, Zahn T, Steegers S, Webb S, Bergman B, O'Brien RM, Hutton JC: Molecular cloning of a pancreatic islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP). |
| 23 | 10480625 | Conservation of an insulin response unit between mouse and human glucose-6-phosphatase catalytic subunit gene promoters: transcription factor FKHR binds the insulin response sequence. |
| 24 | 10480625 | Because overexpression of the glucose-6-phosphatase catalytic subunit (G-6-Pase) in both type 1 and type 2 diabetes may contribute to the characteristic increased rate of hepatic glucose production, we have investigated whether the insulin response unit (IRU) identified in the mouse G-6-Pase promoter is conserved in the human promoter. |
| 25 | 10480625 | We have previously shown that the accessory factor binding region A is hepatocyte nuclear factor-1, and we show here that the forkhead protein FKHR is a candidate for the insulin-responsive transcription factor binding region B. |
| 26 | 10480625 | Conservation of an insulin response unit between mouse and human glucose-6-phosphatase catalytic subunit gene promoters: transcription factor FKHR binds the insulin response sequence. |
| 27 | 10480625 | Because overexpression of the glucose-6-phosphatase catalytic subunit (G-6-Pase) in both type 1 and type 2 diabetes may contribute to the characteristic increased rate of hepatic glucose production, we have investigated whether the insulin response unit (IRU) identified in the mouse G-6-Pase promoter is conserved in the human promoter. |
| 28 | 10480625 | We have previously shown that the accessory factor binding region A is hepatocyte nuclear factor-1, and we show here that the forkhead protein FKHR is a candidate for the insulin-responsive transcription factor binding region B. |
| 29 | 10694370 | Stable overexpression of the glucose-6-phosphatase catalytic subunit attenuates glucose sensitivity of insulin secretion from a mouse pancreatic beta-cell line. |
| 30 | 10694370 | Glucose-6-phosphatase (G-6-Pase) hydrolyzes glucose-6-phosphate to glucose, reciprocal with the so-called glucose sensor, glucokinase, in pancreatic beta cells. |
| 31 | 10694370 | This particular experimental manipulation shows that the possibility exists of modulating glucose-stimulated insulin release by thoroughly altering glucose cycling at the glucokinase/G-6-Pase step. |
| 32 | 11121425 | The clinical manifestations of type 1 glycogen storage disease (GSD-1) in patients deficient in the glucose-6-phosphatase (G6Pase) system (e.g. growth retardation, hepatomegaly, hyperlipidemia, and renal dysfunction) are shared by Hnf1alpha(-/-) mice deficient of a transcriptional activator, hepatocyte nuclear factor 1alpha (HNF1alpha). |
| 33 | 11121425 | Deficiencies in G6Pase and G6PT cause GSD-1a and GSD-1b, respectively. |
| 34 | 11121425 | The clinical manifestations of type 1 glycogen storage disease (GSD-1) in patients deficient in the glucose-6-phosphatase (G6Pase) system (e.g. growth retardation, hepatomegaly, hyperlipidemia, and renal dysfunction) are shared by Hnf1alpha(-/-) mice deficient of a transcriptional activator, hepatocyte nuclear factor 1alpha (HNF1alpha). |
| 35 | 11121425 | Deficiencies in G6Pase and G6PT cause GSD-1a and GSD-1b, respectively. |
| 36 | 11246869 | Characterization of the mouse islet-specific glucose-6-phosphatase catalytic subunit-related protein gene promoter by in situ footprinting: correlation with fusion gene expression in the islet-derived betaTC-3 and hamster insulinoma tumor cell lines. |
| 37 | 11246869 | To begin to investigate the molecular basis for the islet-specific expression of the IGRP gene, a series of truncated IGRP-chloramphenicol acetyltransferase (CAT) fusion genes were transiently transfected into the islet-derived mouse betaTC-3 and hamster insulinoma tumor cell lines. |
| 38 | 11246869 | The data suggest that hepatocyte nuclear factor 3 may be important for basal IGRP gene expression, as it is for glucagon, GLUT2, and Pdx-1 gene expression. |
| 39 | 11940106 | Identification of two novel and potent competitive inhibitors of the glucose-6-phosphatase catalytic protein. |
| 40 | 12160694 | Diabetes mellitus and glycogen storage disease type I (GSDI) may initially appear disparate in metabolic profile: one characterized by uncontrolled hyperglycaemia due to disturbed insulin function and the other by fasting hypoglycaemia caused by impaired gluconeogenesis and glycogenolysis. |
| 41 | 12160694 | DAG plays an important role in the intrarenal renin-angiotensin system via the protein kinase C pathway. |
| 42 | 12815107 | Here, we reveal that the autoantigen targeted by a prevalent population of pathogenic CD8+ T cells in nonobese diabetic mice is islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP). |
| 43 | 14722102 | Enzymatic characterization of the pancreatic islet-specific glucose-6-phosphatase-related protein (IGRP). |
| 44 | 14722102 | Here we present evidence that the previously identified islet-specific glucose-6-phosphatase-related protein (IGRP) is indeed the major islet glucose-6-phosphatase. |
| 45 | 14722102 | These data demonstrate that IGRP is likely the authentic islet-specific glucose-6-phosphatase catalytic subunit, and selective inhibitors to this molecule can be obtained. |
| 46 | 14722102 | IGRP inhibitors may be an attractive new approach for the treatment of insulin secretion defects in type 2 diabetes. |
| 47 | 15180990 | Differential regulation of islet-specific glucose-6-phosphatase catalytic subunit-related protein gene transcription by Pax-6 and Pdx-1. |
| 48 | 15180990 | Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) is selectively expressed in islet beta cells and is a major autoantigen in a mouse model of type I diabetes. |
| 49 | 15180990 | The analysis of IGRP-chloramphenicol acetyltransferase (CAT) fusion gene expression through transient transfection of islet-derived betaTC-3 cells revealed that a promoter region, located between -273 and -254, is essential for high IGRP-CAT fusion gene expression. |
| 50 | 15180990 | Additional experiments revealed a second non-consensus Pax-6 binding site in the -306/-274 IGRP promoter region. |
| 51 | 15180990 | Gel retardation assays revealed that another islet-enriched transcription factor, namely Pdx-1, binds four non-consensus elements in the IGRP promoter. |
| 52 | 15180990 | Although chromatin immunoprecipitation assays show that both Pax-6 and Pdx-1 bind to the IGRP promoter within intact cells, in contrast to the critical role of these factors in beta cell-specific insulin gene expression, IGRP gene transcription appears to require Pax-6 but not Pdx-1. |
| 53 | 15180990 | Differential regulation of islet-specific glucose-6-phosphatase catalytic subunit-related protein gene transcription by Pax-6 and Pdx-1. |
| 54 | 15180990 | Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) is selectively expressed in islet beta cells and is a major autoantigen in a mouse model of type I diabetes. |
| 55 | 15180990 | The analysis of IGRP-chloramphenicol acetyltransferase (CAT) fusion gene expression through transient transfection of islet-derived betaTC-3 cells revealed that a promoter region, located between -273 and -254, is essential for high IGRP-CAT fusion gene expression. |
| 56 | 15180990 | Additional experiments revealed a second non-consensus Pax-6 binding site in the -306/-274 IGRP promoter region. |
| 57 | 15180990 | Gel retardation assays revealed that another islet-enriched transcription factor, namely Pdx-1, binds four non-consensus elements in the IGRP promoter. |
| 58 | 15180990 | Although chromatin immunoprecipitation assays show that both Pax-6 and Pdx-1 bind to the IGRP promoter within intact cells, in contrast to the critical role of these factors in beta cell-specific insulin gene expression, IGRP gene transcription appears to require Pax-6 but not Pdx-1. |
| 59 | 15220199 | The proximal islet-specific glucose-6-phosphatase catalytic subunit-related protein autoantigen promoter is sufficient to initiate but not maintain transgene expression in mouse islets in vivo. |
| 60 | 15220199 | We have previously reported the discovery of an islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) that is predominantly expressed in islet beta-cells. |
| 61 | 15220199 | The analysis of IGRP-chloramphenicol acetyltransferase (CAT) fusion gene expression in transiently transfected islet-derived hamster insulinoma tumor and betaTC-3 cells revealed that the promoter region located between -306 and +3 confers high-level reporter gene expression. |
| 62 | 15220199 | The proximal islet-specific glucose-6-phosphatase catalytic subunit-related protein autoantigen promoter is sufficient to initiate but not maintain transgene expression in mouse islets in vivo. |
| 63 | 15220199 | We have previously reported the discovery of an islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) that is predominantly expressed in islet beta-cells. |
| 64 | 15220199 | The analysis of IGRP-chloramphenicol acetyltransferase (CAT) fusion gene expression in transiently transfected islet-derived hamster insulinoma tumor and betaTC-3 cells revealed that the promoter region located between -306 and +3 confers high-level reporter gene expression. |
| 65 | 15557165 | Individual nonobese diabetic mice exhibit unique patterns of CD8+ T cell reactivity to three islet antigens, including the newly identified widely expressed dystrophia myotonica kinase. |
| 66 | 15557165 | Spontaneous autoimmune diabetes development in NOD mice requires both CD8(+) and CD4(+) T cells. |
| 67 | 15557165 | Although the Ags for G9C8 and 8.3 are known to be insulin and islet-specific glucose-6-phosphatase catalytic subunit-related protein, respectively, only mimotope peptides had previously been identified for AI4. |
| 68 | 15557165 | Screening of a combinatorial peptide library in positional scanning format led to the identification of a peptide derived from dystrophia myotonica kinase (DMK) that is recognized by AI4-like T cells. |
| 69 | 15591035 | Transcriptional regulation of glucose-6-phosphatase catalytic subunit promoter by insulin and glucose in the carnivorous fish, Sparus aurata. |
| 70 | 15591035 | Increase in glucose-6-phosphatase catalytic subunit (G6Pase, G6pc) transcription enhances hepatic glucose production in non-insulin-dependent diabetes mellitus (NIDDM). |
| 71 | 15591035 | Transfection experiments in HepG2 cells showed that insulin repressed S. aurata G6pc under high-glucose conditions. |
| 72 | 15591035 | Synergistic activation of piscine G6pc promoter was induced by cotransfection with expression plasmids for hepatocyte nuclear factor-4alpha (HNF-4alpha) and peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1alpha). |
| 73 | 15591035 | No direct relationship was found between PGC-1alpha coactivation of HNF-4alpha transactivation and the repressive effect of insulin. |
| 74 | 15591035 | Interestingly, insulin hardly affected G6pc promoter activity in the absence of glucose, suggesting that a reduced capacity of insulin-dependent repression of piscine G6pc may lead to insulin resistance in carnivorous fish. |
| 75 | 15591035 | Transcriptional regulation of glucose-6-phosphatase catalytic subunit promoter by insulin and glucose in the carnivorous fish, Sparus aurata. |
| 76 | 15591035 | Increase in glucose-6-phosphatase catalytic subunit (G6Pase, G6pc) transcription enhances hepatic glucose production in non-insulin-dependent diabetes mellitus (NIDDM). |
| 77 | 15591035 | Transfection experiments in HepG2 cells showed that insulin repressed S. aurata G6pc under high-glucose conditions. |
| 78 | 15591035 | Synergistic activation of piscine G6pc promoter was induced by cotransfection with expression plasmids for hepatocyte nuclear factor-4alpha (HNF-4alpha) and peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1alpha). |
| 79 | 15591035 | No direct relationship was found between PGC-1alpha coactivation of HNF-4alpha transactivation and the repressive effect of insulin. |
| 80 | 15591035 | Interestingly, insulin hardly affected G6pc promoter activity in the absence of glucose, suggesting that a reduced capacity of insulin-dependent repression of piscine G6pc may lead to insulin resistance in carnivorous fish. |
| 81 | 15591035 | Transcriptional regulation of glucose-6-phosphatase catalytic subunit promoter by insulin and glucose in the carnivorous fish, Sparus aurata. |
| 82 | 15591035 | Increase in glucose-6-phosphatase catalytic subunit (G6Pase, G6pc) transcription enhances hepatic glucose production in non-insulin-dependent diabetes mellitus (NIDDM). |
| 83 | 15591035 | Transfection experiments in HepG2 cells showed that insulin repressed S. aurata G6pc under high-glucose conditions. |
| 84 | 15591035 | Synergistic activation of piscine G6pc promoter was induced by cotransfection with expression plasmids for hepatocyte nuclear factor-4alpha (HNF-4alpha) and peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1alpha). |
| 85 | 15591035 | No direct relationship was found between PGC-1alpha coactivation of HNF-4alpha transactivation and the repressive effect of insulin. |
| 86 | 15591035 | Interestingly, insulin hardly affected G6pc promoter activity in the absence of glucose, suggesting that a reduced capacity of insulin-dependent repression of piscine G6pc may lead to insulin resistance in carnivorous fish. |
| 87 | 15591035 | Transcriptional regulation of glucose-6-phosphatase catalytic subunit promoter by insulin and glucose in the carnivorous fish, Sparus aurata. |
| 88 | 15591035 | Increase in glucose-6-phosphatase catalytic subunit (G6Pase, G6pc) transcription enhances hepatic glucose production in non-insulin-dependent diabetes mellitus (NIDDM). |
| 89 | 15591035 | Transfection experiments in HepG2 cells showed that insulin repressed S. aurata G6pc under high-glucose conditions. |
| 90 | 15591035 | Synergistic activation of piscine G6pc promoter was induced by cotransfection with expression plasmids for hepatocyte nuclear factor-4alpha (HNF-4alpha) and peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1alpha). |
| 91 | 15591035 | No direct relationship was found between PGC-1alpha coactivation of HNF-4alpha transactivation and the repressive effect of insulin. |
| 92 | 15591035 | Interestingly, insulin hardly affected G6pc promoter activity in the absence of glucose, suggesting that a reduced capacity of insulin-dependent repression of piscine G6pc may lead to insulin resistance in carnivorous fish. |
| 93 | 15591035 | Transcriptional regulation of glucose-6-phosphatase catalytic subunit promoter by insulin and glucose in the carnivorous fish, Sparus aurata. |
| 94 | 15591035 | Increase in glucose-6-phosphatase catalytic subunit (G6Pase, G6pc) transcription enhances hepatic glucose production in non-insulin-dependent diabetes mellitus (NIDDM). |
| 95 | 15591035 | Transfection experiments in HepG2 cells showed that insulin repressed S. aurata G6pc under high-glucose conditions. |
| 96 | 15591035 | Synergistic activation of piscine G6pc promoter was induced by cotransfection with expression plasmids for hepatocyte nuclear factor-4alpha (HNF-4alpha) and peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1alpha). |
| 97 | 15591035 | No direct relationship was found between PGC-1alpha coactivation of HNF-4alpha transactivation and the repressive effect of insulin. |
| 98 | 15591035 | Interestingly, insulin hardly affected G6pc promoter activity in the absence of glucose, suggesting that a reduced capacity of insulin-dependent repression of piscine G6pc may lead to insulin resistance in carnivorous fish. |
| 99 | 15728483 | Different diabetogenic potential of autoaggressive CD8+ clones associated with IFN-gamma-inducible protein 10 (CXC chemokine ligand 10) production but not cytokine expression, cytolytic activity, or homing characteristics. |
| 100 | 15728483 | From studies in animal models, CD8(+) T cells recognizing autoantigens such as islet-specific glucose-6-phosphatase catalytic subunit-related protein, insulin, or glutamic acid decarboxylase (GAD) are believed to play important roles in both the early and late phases of beta cell destruction. |
| 101 | 15728483 | In this study, we investigated the factors governing the diabetogenic potential of autoreactive CD8(+) clones isolated from spleens of NOD mice that had been immunized with GAD65(515-524) or insulin B-chain(15-23) peptides. |
| 102 | 15728483 | Although these two clones were identical in most phenotypic and functional aspects, for example cytokine production and killing of autologous beta cells, they differed in the expression of IFN-gamma-inducible protein-10, which was only produced at high levels by the insulin-specific clone, but not by the GAD65-specific clone, and other autoantigen-specific nonpathogenic CD8 T cell clones. |
| 103 | 15728483 | Interestingly, upon i.p. injection into neonatal mice, only the insulin B-chain(15-23)-reactive CD8(+) T clone accelerated diabetes in all recipients after 4 wk, although both insulin- and GAD-reactive clones homed to pancreas and pancreatic lymph nodes with similar kinetics. |
| 104 | 15728483 | Thus, secretion of IFN-gamma-inducible protein-10 by autoaggressive CD8(+) lymphocytes might determine their diabetogenic capacity by affecting recruitment of cells to the insulitic lesion. |
| 105 | 15843527 | Identification of CD4+ T cell-specific epitopes of islet-specific glucose-6-phosphatase catalytic subunit-related protein: a novel beta cell autoantigen in type 1 diabetes. |
| 106 | 15843527 | Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) has been identified as a novel CD8(+) T cell-specific autoantigen in NOD mice. |
| 107 | 15843527 | This study was undertaken to identify MHC class II-specific CD4(+) T cell epitopes of IGRP. |
| 108 | 15843527 | Experiments using purified CD4(+) and CD8(+) T cells from IGRP peptide-primed mice also showed a predominant CD4(+) T cell response with no significant activation of CD8(+) T cells. |
| 109 | 15843527 | T cells from P1-, P3-, and P7-primed mice secreted both IFN-gamma and IL-10 cytokines, whereas P2-primed cells secreted only IFN-gamma. |
| 110 | 15843527 | In summary, we have identified two I-A(g7)-restricted CD4(+) T cell epitopes of IGRP that can modulate and prevent the development of diabetes in NOD mice. |
| 111 | 15843527 | These results provide the first evidence on the role of IGRP-specific, MHC class II-restricted CD4(+) T cells in disease protection and may help in the development of novel therapies for type 1 diabetes. |
| 112 | 15843527 | Identification of CD4+ T cell-specific epitopes of islet-specific glucose-6-phosphatase catalytic subunit-related protein: a novel beta cell autoantigen in type 1 diabetes. |
| 113 | 15843527 | Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) has been identified as a novel CD8(+) T cell-specific autoantigen in NOD mice. |
| 114 | 15843527 | This study was undertaken to identify MHC class II-specific CD4(+) T cell epitopes of IGRP. |
| 115 | 15843527 | Experiments using purified CD4(+) and CD8(+) T cells from IGRP peptide-primed mice also showed a predominant CD4(+) T cell response with no significant activation of CD8(+) T cells. |
| 116 | 15843527 | T cells from P1-, P3-, and P7-primed mice secreted both IFN-gamma and IL-10 cytokines, whereas P2-primed cells secreted only IFN-gamma. |
| 117 | 15843527 | In summary, we have identified two I-A(g7)-restricted CD4(+) T cell epitopes of IGRP that can modulate and prevent the development of diabetes in NOD mice. |
| 118 | 15843527 | These results provide the first evidence on the role of IGRP-specific, MHC class II-restricted CD4(+) T cells in disease protection and may help in the development of novel therapies for type 1 diabetes. |
| 119 | 15908957 | Here, we examine the antidiabetogenic properties of altered peptide ligands of CD8+ T cells recognizing an epitope of islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP206-214), a prevalent population of autoreactive T cells in autoimmune diabetes. |
| 120 | 15908957 | We show that islet-associated CD8+ T cells in nonobese diabetic mice recognize numerous IGRP epitopes, and that these cells have a role in the outcome of protocols designed to induce IGRP206-214-specific tolerance. |
| 121 | 15937548 | We have carried out comprehensive studies of the diabetogenic CD8 T cell population that targets residues 206-214 of the beta cell antigen islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP(206-214)) and undergoes avidity maturation as disease progresses. |
| 122 | 16295523 | The autoantigens of Type 1A diabetes may be divided into subgroups based on their tissue distributions: Beta-cell-specific antigens like insulin, insulin derivatives, and IGRP (Islet-specific Glucose-6-phosphatase catalytic subunit Related Peptide); neurendocrine antigens such as carboxypeptidase H, insulinoma-associated antigen (IA-2), glutamic acid decarboxylase (GAD65), and carboxypeptidase E; and those expressed ubiquitously like heat shock protein 60 (a putative autoantigen for type 1 diabetes). |
| 123 | 16374520 | Irs1 and Irs2 signaling is essential for hepatic glucose homeostasis and systemic growth. |
| 124 | 16374520 | Insulin receptor substrates, including Irs1 and Irs2, integrate insulin and IGF receptor signals with heterologous pathways to coordinate growth and metabolism. |
| 125 | 16374520 | Since Irs2 is thought to be especially important in hepatic nutrient homeostasis, we deleted Irs2 [corrected] from hepatocytes of WT mice (called LKO) or genetically insulin-resistant Irs1-/- mice (called LKO::Irs1-/-). |
| 126 | 16374520 | Hepatic insulin receptors were functional in all the mice, but insulin signaling via the Akt-FoxO1 pathway was reduced in Irs1-/- and LKO liver, and undetected in LKO::Irs1-/- liver; however, Gsk3beta phosphorylation (Ser9) and hepatic glycogen stores were nearly normal in all of the mice. |
| 127 | 16374520 | Regardless, few hepatic genes changed expression significantly in Irs1-/- or LKO mice, whereas hundreds of genes changed in LKO::Irs1-/- mice--including elevated levels of Pck1, G6pc, Ppargc1, Pparg, and Igfbp1. |
| 128 | 16374520 | Thus, signals delivered by Irs1 or Irs2 regulate hepatic gene expression that coordinates glucose homeostasis and systemic growth. |
| 129 | 16380490 | No significant differences in plasma corticosterone, splenic CD4(+) or CD8(+) T-cell percentages, or functions of CD3(+) T-cells in vitro distinguished NOD wild-type from mutant mice. |
| 130 | 16380490 | This correlated with significantly reduced (P < 0.01) frequencies of insulin and islet-specific glucose-6-phosphatase catalytic subunit-related protein-reactive CD8(+) T-effector clonotypes in mutant mice. |
| 131 | 16380490 | In conclusion, metabolic disturbances elicited by a type 2 diabetes syndrome (insulin and/or leptin resistance, but not hypercorticism) appear to suppress type 1 diabetes development in NOD-Lepr(db-5J)/Lt by inhibiting activation of T-effector cells. |
| 132 | 16424193 | Early autoimmune destruction of islet grafts is associated with a restricted repertoire of IGRP-specific CD8+ T cells in diabetic nonobese diabetic mice. |
| 133 | 16424193 | In endogenous islets, CD8+ T cells specific for an islet-specific glucose-6-phosphatase catalytic subunit-related protein derived peptide (IGRP206-214) were the most prevalent T cells. |
| 134 | 16493034 | Islet-specific glucose-6-phosphatase catalytic subunit-related protein-reactive CD4+ T cells in human subjects. |
| 135 | 16493034 | Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) is recognized as a major autoantigen for autoimmune type 1 diabetes (T1D) in the NOD mouse model. |
| 136 | 16493034 | This study was undertaken to examine CD4+ T cell responses toward IGRP in human subjects. |
| 137 | 16493034 | The tetramer-guided epitope mapping approach was used to identify IGRP-specific CD4+ T cell epitopes. |
| 138 | 16493034 | More than 80% of subjects with either DRB1*0401 or DRB1*0301 haplotype have IGRP-specific CD4+ T cell responses for at least one IGRP epitope. |
| 139 | 16493034 | IGRP-specific T cells from both healthy and T1D groups produce both gamma-IFN and IL-10. |
| 140 | 16493034 | DRA1*0101/DRB1*0401 IGRP(247-259)-restricted T cells also show cross-reactivity to an epitope derived from liver/kidney glucose-6-phosphatase. |
| 141 | 16493034 | Islet-specific glucose-6-phosphatase catalytic subunit-related protein-reactive CD4+ T cells in human subjects. |
| 142 | 16493034 | Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) is recognized as a major autoantigen for autoimmune type 1 diabetes (T1D) in the NOD mouse model. |
| 143 | 16493034 | This study was undertaken to examine CD4+ T cell responses toward IGRP in human subjects. |
| 144 | 16493034 | The tetramer-guided epitope mapping approach was used to identify IGRP-specific CD4+ T cell epitopes. |
| 145 | 16493034 | More than 80% of subjects with either DRB1*0401 or DRB1*0301 haplotype have IGRP-specific CD4+ T cell responses for at least one IGRP epitope. |
| 146 | 16493034 | IGRP-specific T cells from both healthy and T1D groups produce both gamma-IFN and IL-10. |
| 147 | 16493034 | DRA1*0101/DRB1*0401 IGRP(247-259)-restricted T cells also show cross-reactivity to an epitope derived from liver/kidney glucose-6-phosphatase. |
| 148 | 16493087 | In both humans and NOD mice, particular MHC genes are primary contributors to development of the autoreactive CD4+ and CD8+ T cell responses against pancreatic beta cells that cause type 1 diabetes (T1D). |
| 149 | 16493087 | In this study, we show that transgenic expression in NOD mice of HLA-A*0201, in the absence of murine class I MHC molecules, is sufficient to mediate autoreactive CD8+ T cell responses contributing to T1D development. |
| 150 | 16493087 | CD8+ T cells from the transgenic mice are cytotoxic to murine and human HLA-A*0201-positive islet cells. |
| 151 | 16493087 | Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) is one of several important T1D autoantigens in standard NOD mice. |
| 152 | 16493087 | Three IGRP-derived peptides were identified as targets of diabetogenic HLA-A*0201-restricted T cells in our NOD transgenic stock. |
| 153 | 16520917 | Alternative splicing of G6PC2, the gene coding for the islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP), results in differential expression in human thymus and spleen compared with pancreas. |
| 154 | 16728432 | We have shown that development of autoimmune diabetes in non-obese diabetic (NOD) mice involves prevalent recruitment of CD8+ T cells recognizing epitopes of islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP). |
| 155 | 16979383 | We have identified for the first time an age-dependent spontaneous loss of tolerance to two self-antigenic epitopes derived from putative diabetes-associated antigens glutamic acid decarboxylase (GAD65) and glial fibrillary acidic protein (GFAP) in RIP-B7/DRB1*0404 HLA transgenic mice. |
| 156 | 16979383 | Diabetic and older non-diabetic mice exhibited a proliferative response to an immunodominant epitope from GAD65 (555-567) and also from GFAP (240-252) but not from an immunogenic epitope from diabetes-associated islet-specific glucose-6-phosphatase catalytic subunit-related protein. |
| 157 | 16979383 | Islet infiltrates in older non-diabetic mice and diabetic mice contain CD4(+)/FoxP3(+) cells and suggest the presence of a regulatory mechanism prior and during diabetic disease. |
| 158 | 17065343 | In an effort to identify novel epitopes, we used matrix-assisted algorithms to predict peptides of glial fibrillary acidic protein (GFAP), prepro-islet amyloid polypeptide (ppIAPP), and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) that likely bind to HLA-A*0201 with a strong affinity and contain a COOH-terminal proteasomal cleavage site. |
| 159 | 17065343 | Seven peptides stabilized HLA-A*0201 expression in binding assays and were used to stimulate peripheral blood mononuclear cells and were evaluated for granzyme B secretion. |
| 160 | 17065343 | Other peptides recognized by type 1 diabetic or antibody-positive subjects included GFAP(143-151), IGRP(152-160), and GFAP(214-222). |
| 161 | 17065343 | These data implicate peptides of ppIAPP, GFAP, and IGRP as CTL epitopes for a heterogenous CD8(+) T-cell response in type 1 subjects and antibody-positive relatives. |
| 162 | 17065344 | To identify additional epitopes, HLA class I peptide affinity algorithms were used to identify a panel of peptides derived from the beta-cell proteins islet amyloid polypeptide (IAPP), islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP), insulin, insulinoma-associated antigen 2 (IA-2), and phogrin that were predicted to bind HLA-A*0201. |
| 163 | 17065344 | We identified peptides IAPP9-17, IGRP215-223, IGRP152-160, islet IA-2(172-180), and IA-2(482-490) as novel HLA-A*0201-restricted T-cell epitopes in type 1 diabetic patients. |
| 164 | 17143326 | In a study of NOD mice in this issue of the JCI, Krishnamurthy et al. show that the autoreactive T cell response to the autoantigen proinsulin lies upstream of that to islet-specific glucose-6-phosphatase catalytic subunit-related protein, suggesting that the pathogenic autoimmune response to proinsulin subsequently spreads to other antigens (see the related article beginning on page 3258). |
| 165 | 17143333 | Responses against islet antigens in NOD mice are prevented by tolerance to proinsulin but not IGRP. |
| 166 | 17143333 | T cells specific for proinsulin and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) can induce T1D in NOD mice. |
| 167 | 17143333 | As cytotoxic T cells specific for IGRP were not detected in transgenic NOD mice tolerant to proinsulin, we determined that immune responses against proinsulin are necessary for IGRP-specific T cells to develop. |
| 168 | 17143333 | On the other hand, transgenic overexpression of IGRP resulted in loss of intra-islet IGRP-specific T cells but did not protect NOD mice from insulitis or T1D, providing direct evidence that the response against IGRP is downstream of the response to proinsulin. |
| 169 | 17143333 | Our results suggest that pathogenic proinsulin-specific immunity in NOD mice subsequently spreads to other antigens such as IGRP. |
| 170 | 17265032 | Deletion of the gene encoding the islet-specific glucose-6-phosphatase catalytic subunit-related protein autoantigen results in a mild metabolic phenotype. |
| 171 | 17327428 | Although CD4+ T-cell assays have met with limited success, CD8+ T-cells are increasingly recognized as key actors in the diabetes of the NOD mouse. |
| 172 | 17327428 | Taking advantage of a panel of HLA-A2-restricted beta-cell epitopes derived from preproinsulin, GAD, and islet glucose-6-phosphatase catalytic subunit-related protein (IGRP), we have implemented an islet-specific CD8+ T-cell interferon-gamma enzyme-linked immunospot (ISL8Spot) assay. |
| 173 | 17376821 | Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) is an important antigenic target of diabetogenic CD8 cells in standard NOD mice. |
| 174 | 17376840 | Human clonal CD8 autoreactivity to an IGRP islet epitope shared between mice and men. |
| 175 | 17376840 | The aim of this study was to assess whether an epitope derived from the islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP), IGRP(265-273,) which has recently been identified as a target in non-obese diabetic (NOD) mice and is fully homologous to the human epitope, is a target of human diabetogenic CD8(+) T cells. |
| 176 | 17376840 | We isolated a human CD8 T cell clone against this epitope, which confirms that this IGRP epitope is shared across species. |
| 177 | 17395746 | Although the frequency of nucleoprotein-specific CD8 T-cells in the pancreatic draining lymph node was comparable with the frequency of islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)-specific T-cells, more IGRP-specific CD8 T-cells were found both systemically and in the islets where there was a fourfold increase. |
| 178 | 17395746 | Interestingly, and in contrast to nucleoprotein-specific CD8 T-cells, IGRP-specific T-cells showed increased CXCR3 expression. |
| 179 | 17565413 | Endoplasmic reticulum stress caused by overexpression of islet-specific glucose-6-phosphatase catalytic subunit-related protein in pancreatic Beta-cells. |
| 180 | 17565413 | Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) is an ER-resident protein that is specifically expressed in pancreatic beta-cells and is a major target of diabetogenic CD8(+) T cell responses in non-obese diabetic (NOD) mice. |
| 181 | 17565413 | We produced transgenic mice expressing human IGRP (hIGRP) under the control of rat insulin promoter (RIP) to study epitopes in hIGRP capable of driving diabetogenic human leukocyte antigen (HLA)-restricted CD8(+) T-cell responses in hIGRP/HLA transgenic NOD mice. |
| 182 | 17565413 | Endoplasmic reticulum stress caused by overexpression of islet-specific glucose-6-phosphatase catalytic subunit-related protein in pancreatic Beta-cells. |
| 183 | 17565413 | Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) is an ER-resident protein that is specifically expressed in pancreatic beta-cells and is a major target of diabetogenic CD8(+) T cell responses in non-obese diabetic (NOD) mice. |
| 184 | 17565413 | We produced transgenic mice expressing human IGRP (hIGRP) under the control of rat insulin promoter (RIP) to study epitopes in hIGRP capable of driving diabetogenic human leukocyte antigen (HLA)-restricted CD8(+) T-cell responses in hIGRP/HLA transgenic NOD mice. |
| 185 | 17942825 | Long-range enhancers are required to maintain expression of the autoantigen islet-specific glucose-6-phosphatase catalytic subunit-related protein in adult mouse islets in vivo. |
| 186 | 18302224 | The contrast agent is an MRI probe (MN-NRP-V7) that specifically labels CD8+ T-cells recognizing residues 206-214 of islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP(206-214)) in the context of the major histocompatibility complex (MHC) class I molecule H-2K(d). |
| 187 | 18354167 | Autoimmunity to both proinsulin and IGRP is required for diabetes in nonobese diabetic 8.3 TCR transgenic mice. |
| 188 | 18354167 | T cells specific for proinsulin and islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP) induce diabetes in nonobese diabetic (NOD) mice. |
| 189 | 18354167 | TCR transgenic mice with CD8(+) T cells specific for IGRP(206-214) (NOD8.3 mice) develop accelerated diabetes that requires CD4(+) T cell help. |
| 190 | 18354167 | We previously showed that immune responses against proinsulin are necessary for IGRP(206-214)-specific CD8(+) T cells to expand. |
| 191 | 18354167 | This indicates that immunity to proinsulin is even required in the great majority of NOD8.3 mice that have a pre-existing repertoire of IGRP(206-214)-specific cells. |
| 192 | 18354167 | This suggests that islet inflammation can substitute for proinsulin-specific CD4(+) T cell help to activate IGRP(206-214)-specific T cells. |
| 193 | 18451265 | SNP rs560887 maps to intron 3 of the G6PC2 gene, which encodes glucose-6-phosphatase catalytic subunit-related protein (also known as IGRP), a protein selectively expressed in pancreatic islets. |
| 194 | 18451265 | We speculate that G6PC2 regulates FPG by modulating the set point for glucose-stimulated insulin secretion in pancreatic beta cells. |
| 195 | 18521185 | Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels. |
| 196 | 18521185 | The rs563694 SNP is located between the genes glucose-6-phosphatase catalytic subunit 2 (G6PC2) and ATP-binding cassette, subfamily B (MDR/TAP), member 11 (ABCB11). |
| 197 | 18521185 | Our results in combination with data reported in the literature suggest that G6PC2, a glucose-6-phosphatase almost exclusively expressed in pancreatic islet cells, may underlie variation in fasting glucose, though it is possible that ABCB11, which is expressed primarily in liver, may also contribute to such variation. |
| 198 | 18753309 | Foxa2 and MafA regulate islet-specific glucose-6-phosphatase catalytic subunit-related protein gene expression. |
| 199 | 18753309 | Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP/G6PC2) is a major autoantigen in both mouse and human type 1 diabetes. |
| 200 | 18753309 | Chromatin immunoprecipitation (ChIP) assays have shown that the IGRP promoter binds the islet-enriched transcription factors Pax-6 and BETA2. |
| 201 | 18753309 | We show here, again using ChIP assays, that the IGRP promoter also binds the islet-enriched transcription factors MafA and Foxa2. |
| 202 | 18753309 | ChiP assays have shown that the islet-enriched transcription factor Pdx-1 also binds the IGRP promoter, but mutational analysis of four Pdx-1 binding sites in the proximal IGRP promoter revealed surprisingly little effect of Pdx-1 binding on IGRP fusion gene expression in betaTC-3 cells. |
| 203 | 18753309 | These data suggest that the same group of islet-enriched transcription factors, namely Pdx-1, Pax-6, MafA, BETA2, and Foxa2, directly or indirectly regulate expression of the two major autoantigens in type 1 diabetes. |
| 204 | 18753309 | Foxa2 and MafA regulate islet-specific glucose-6-phosphatase catalytic subunit-related protein gene expression. |
| 205 | 18753309 | Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP/G6PC2) is a major autoantigen in both mouse and human type 1 diabetes. |
| 206 | 18753309 | Chromatin immunoprecipitation (ChIP) assays have shown that the IGRP promoter binds the islet-enriched transcription factors Pax-6 and BETA2. |
| 207 | 18753309 | We show here, again using ChIP assays, that the IGRP promoter also binds the islet-enriched transcription factors MafA and Foxa2. |
| 208 | 18753309 | ChiP assays have shown that the islet-enriched transcription factor Pdx-1 also binds the IGRP promoter, but mutational analysis of four Pdx-1 binding sites in the proximal IGRP promoter revealed surprisingly little effect of Pdx-1 binding on IGRP fusion gene expression in betaTC-3 cells. |
| 209 | 18753309 | These data suggest that the same group of islet-enriched transcription factors, namely Pdx-1, Pax-6, MafA, BETA2, and Foxa2, directly or indirectly regulate expression of the two major autoantigens in type 1 diabetes. |
| 210 | 19060180 | Role of the E3 ubiquitin ligase gene related to anergy in lymphocytes in glucose and lipid metabolism in the liver. |
| 211 | 19060180 | Gene related to anergy in lymphocytes (GRAIL) is an E3 ubiquitin ligase that regulates energy in T-lymphocytes. |
| 212 | 19060180 | Adenovirus-mediated transfer of a short hairpin RNA specific for GRAIL mRNA markedly reduced the amounts of GRAIL mRNA and protein in the liver. |
| 213 | 19060180 | The hepatic abundance of mRNAs for glucose-6-phosphatase, catalytic (a key enzyme in hepatic glucose production) and for sterol regulatory element-binding transcription factor 1 (an important transcriptional regulator of lipogenesis) was increased in the mice with hepatic GRAIL deficiency, possibly contributing to the metabolic abnormalities of these animals. |
| 214 | 19188044 | Several antigens such as insulin, glutamic acid decarboxylase (GAD) and islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP) are considered to take part in the autoimmune destructive process. |
| 215 | 19188044 | Because the role of GAD in the disease process of type 1 diabetes is still controversial, we investigated the disease phenotype upon in vivo induction of whole GAD65 reactivity using a GAD65 homo knockout NOD splenocytes to NOD-scid transfer system. |
| 216 | 19188044 | Splenocytes from recipients of KOT splenocytes produced IL-10 (/IFN-gamma) upon GAD65 stimulation, whereas those from recipients of WTT splenocytes did not. |
| 217 | 19209463 | A very significant fraction of islet-associated CD8 T cells in NOD mice recognize epitopes of islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP), a non-essential endoplasmic reticulum-resident protein of unclear function. |
| 218 | 19209463 | IGRP is also a target of CD8 T cell responses in human T1D patients. |
| 219 | 19209463 | In NOD mice, most IGRP-reactive CD8 T cells target the IGRP(206-214) epitope and are diabetogenic. |
| 220 | 19209463 | In mice, Il2 polymorphisms control a negative feedback mechanism initiated by activated, IL2-producing autoreactive T cells in the pancreatic lymph nodes that increases the regulatory activity of CD4+CD25+ T cells. |
| 221 | 19209463 | Not all IGRP-reactive CD8 T cell clones are pathogenic, however, and we have evidence that some of these clonotypes are actually anti-diabetogenic. |
| 222 | 19209463 | We had previously shown that administration of altered peptide ligands (APL) targeting IGRP(206-214)-reactive CD8 T cells resulted in diabetes protection only at doses that did not delete low-avidity clones, suggesting a protective role for these clonotypes. |
| 223 | 19209463 | Here I briefly summarize work done by us and others indicating that a prevalent subset of autoreactive CD8 T-cells in the NOD mouse are major (albeit likely dispensable) players in the pathogenesis of spontaneous autoimmune diabetes in the NOD mouse; that these T cells are targets of genetic elements affording autoimmune disease susceptibility and resistance; that they can either be diabetogenic or anti-diabetogenic according to their avidity for peptide/MHC; and that they can serve as useful targets for therapeutic intervention. |
| 224 | 19587243 | Fasting hyperglycemia is not associated with increased expression of PEPCK or G6Pc in patients with Type 2 Diabetes. |
| 225 | 19587243 | Fasting hyperglycemia in patients with type 2 diabetes mellitus (T2DM) is attributed to increased hepatic gluconeogenesis, which has been ascribed to increased transcriptional expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase, catalytic (G6Pc). |
| 226 | 19587243 | In a second model, control and HFF rats were infused with somatostatin, followed by portal vein infusion of insulin and glucagon. |
| 227 | 19587243 | Surprisingly, the expression of PEPCK or G6Pc was not increased. |
| 228 | 19587243 | However, PEPCK and G6Pc expression remained unchanged. |
| 229 | 19587243 | Finally, in patients with T2DM, hepatic expression of PEPCK or G6Pc was not increased. |
| 230 | 19587243 | Thus, in contrast to current dogma, these data demonstrate that increased transcriptional expression of PEPCK1 and G6Pc does not account for increased gluconeogenesis and fasting hyperglycemia in patients with T2DM. |
| 231 | 19587243 | Fasting hyperglycemia is not associated with increased expression of PEPCK or G6Pc in patients with Type 2 Diabetes. |
| 232 | 19587243 | Fasting hyperglycemia in patients with type 2 diabetes mellitus (T2DM) is attributed to increased hepatic gluconeogenesis, which has been ascribed to increased transcriptional expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase, catalytic (G6Pc). |
| 233 | 19587243 | In a second model, control and HFF rats were infused with somatostatin, followed by portal vein infusion of insulin and glucagon. |
| 234 | 19587243 | Surprisingly, the expression of PEPCK or G6Pc was not increased. |
| 235 | 19587243 | However, PEPCK and G6Pc expression remained unchanged. |
| 236 | 19587243 | Finally, in patients with T2DM, hepatic expression of PEPCK or G6Pc was not increased. |
| 237 | 19587243 | Thus, in contrast to current dogma, these data demonstrate that increased transcriptional expression of PEPCK1 and G6Pc does not account for increased gluconeogenesis and fasting hyperglycemia in patients with T2DM. |
| 238 | 19587243 | Fasting hyperglycemia is not associated with increased expression of PEPCK or G6Pc in patients with Type 2 Diabetes. |
| 239 | 19587243 | Fasting hyperglycemia in patients with type 2 diabetes mellitus (T2DM) is attributed to increased hepatic gluconeogenesis, which has been ascribed to increased transcriptional expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase, catalytic (G6Pc). |
| 240 | 19587243 | In a second model, control and HFF rats were infused with somatostatin, followed by portal vein infusion of insulin and glucagon. |
| 241 | 19587243 | Surprisingly, the expression of PEPCK or G6Pc was not increased. |
| 242 | 19587243 | However, PEPCK and G6Pc expression remained unchanged. |
| 243 | 19587243 | Finally, in patients with T2DM, hepatic expression of PEPCK or G6Pc was not increased. |
| 244 | 19587243 | Thus, in contrast to current dogma, these data demonstrate that increased transcriptional expression of PEPCK1 and G6Pc does not account for increased gluconeogenesis and fasting hyperglycemia in patients with T2DM. |
| 245 | 19587243 | Fasting hyperglycemia is not associated with increased expression of PEPCK or G6Pc in patients with Type 2 Diabetes. |
| 246 | 19587243 | Fasting hyperglycemia in patients with type 2 diabetes mellitus (T2DM) is attributed to increased hepatic gluconeogenesis, which has been ascribed to increased transcriptional expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase, catalytic (G6Pc). |
| 247 | 19587243 | In a second model, control and HFF rats were infused with somatostatin, followed by portal vein infusion of insulin and glucagon. |
| 248 | 19587243 | Surprisingly, the expression of PEPCK or G6Pc was not increased. |
| 249 | 19587243 | However, PEPCK and G6Pc expression remained unchanged. |
| 250 | 19587243 | Finally, in patients with T2DM, hepatic expression of PEPCK or G6Pc was not increased. |
| 251 | 19587243 | Thus, in contrast to current dogma, these data demonstrate that increased transcriptional expression of PEPCK1 and G6Pc does not account for increased gluconeogenesis and fasting hyperglycemia in patients with T2DM. |
| 252 | 19587243 | Fasting hyperglycemia is not associated with increased expression of PEPCK or G6Pc in patients with Type 2 Diabetes. |
| 253 | 19587243 | Fasting hyperglycemia in patients with type 2 diabetes mellitus (T2DM) is attributed to increased hepatic gluconeogenesis, which has been ascribed to increased transcriptional expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase, catalytic (G6Pc). |
| 254 | 19587243 | In a second model, control and HFF rats were infused with somatostatin, followed by portal vein infusion of insulin and glucagon. |
| 255 | 19587243 | Surprisingly, the expression of PEPCK or G6Pc was not increased. |
| 256 | 19587243 | However, PEPCK and G6Pc expression remained unchanged. |
| 257 | 19587243 | Finally, in patients with T2DM, hepatic expression of PEPCK or G6Pc was not increased. |
| 258 | 19587243 | Thus, in contrast to current dogma, these data demonstrate that increased transcriptional expression of PEPCK1 and G6Pc does not account for increased gluconeogenesis and fasting hyperglycemia in patients with T2DM. |
| 259 | 19587243 | Fasting hyperglycemia is not associated with increased expression of PEPCK or G6Pc in patients with Type 2 Diabetes. |
| 260 | 19587243 | Fasting hyperglycemia in patients with type 2 diabetes mellitus (T2DM) is attributed to increased hepatic gluconeogenesis, which has been ascribed to increased transcriptional expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase, catalytic (G6Pc). |
| 261 | 19587243 | In a second model, control and HFF rats were infused with somatostatin, followed by portal vein infusion of insulin and glucagon. |
| 262 | 19587243 | Surprisingly, the expression of PEPCK or G6Pc was not increased. |
| 263 | 19587243 | However, PEPCK and G6Pc expression remained unchanged. |
| 264 | 19587243 | Finally, in patients with T2DM, hepatic expression of PEPCK or G6Pc was not increased. |
| 265 | 19587243 | Thus, in contrast to current dogma, these data demonstrate that increased transcriptional expression of PEPCK1 and G6Pc does not account for increased gluconeogenesis and fasting hyperglycemia in patients with T2DM. |
| 266 | 19700406 | Glucose-6-phosphatase catalytic subunit gene family. |
| 267 | 19700406 | The G6PC gene family contains three members, designated G6PC, G6PC2, and G6PC3. |
| 268 | 19700406 | Glucose-6-phosphatase catalytic subunit gene family. |
| 269 | 19700406 | The G6PC gene family contains three members, designated G6PC, G6PC2, and G6PC3. |
| 270 | 19886740 | Unexpectedly, the ratio of CD4(+):CD8(+) T cells was tightly controlled in the islets throughout diabetogenesis. |
| 271 | 19886740 | The frequency of IL-4(+) CD4(+) T cells started high but quickly fell to 3% of the population that was maintained with increasing inflammation. |
| 272 | 19886740 | A significant portion of the CD8(+) T cells were islet-specific glucose-6-phosphatase catalytic subunit-related protein specific in both male and female NOD mice and this population was antigen experienced and increased at high levels of islet inflammation. |
| 273 | 20004937 | Post-mortem heart sections were immunohistochemically stained for collagen types I and III and connective tissue growth factor (CTGF). |
| 274 | 20004937 | Genomic DNA was prepared from post-mortem samples, and genetic analysis was performed in the SCN5A, G6PC, PHOX2B, and CTGF genes. |
| 275 | 20004937 | Twenty-two dead in bed syndrome cases were identified and staining of heart sections for collagen I and III, and CTGF showed no differences between dead in bed syndrome cases and controls. |
| 276 | 20004937 | No genetic variants were found in G6PC, PHOX2B, and CTGF, and dead in bed syndrome cases were not associated with the G-945C CTGF promoter polymorphism. |
| 277 | 20004937 | Post-mortem heart sections were immunohistochemically stained for collagen types I and III and connective tissue growth factor (CTGF). |
| 278 | 20004937 | Genomic DNA was prepared from post-mortem samples, and genetic analysis was performed in the SCN5A, G6PC, PHOX2B, and CTGF genes. |
| 279 | 20004937 | Twenty-two dead in bed syndrome cases were identified and staining of heart sections for collagen I and III, and CTGF showed no differences between dead in bed syndrome cases and controls. |
| 280 | 20004937 | No genetic variants were found in G6PC, PHOX2B, and CTGF, and dead in bed syndrome cases were not associated with the G-945C CTGF promoter polymorphism. |
| 281 | 20022654 | Rare monogenic syndromes, such as alpha1-antitrypsin deficiency, glycogen storage disease type I, hemochromatosis, acute intermittent and cutanea tarda porphyria, as well as hereditary tyrosinemia type I are associated with a high risk of HCC. |
| 282 | 20217518 | Evidence for an autoimmune origin of T1D results from measurable islet beta-cell autoantibody directed against various autoantigens such as proinsulin or insulin itself, glutamic acid decarboxylase 65, the islet tyrosine phosphatase IA-2, and the islet-specific glucose-6-phosphatase catalytic subunit-related protein. |
| 283 | 20220085 | Toxin-coupled MHC class I tetramers can specifically ablate autoreactive CD8+ T cells and delay diabetes in nonobese diabetic mice. |
| 284 | 20220085 | We show that saporin-coupled tetramers can delete islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)-reactive T cells in vitro and in vivo. |
| 285 | 20220085 | Finally, we show deletion at 8 wk of age of IGRP(+) CD8(+) T cells, but not dystophia myotonica kinase- or insulin B-reactive cells, significantly delays diabetes in NOD mice. |
| 286 | 20439719 | We monitored the recruitment of CD8(+) T cells specific for the prevalent diabetogenic epitope islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)(206-214) in gene-targeted nonobese diabetic (NOD) mice expressing a T cell "invisible" IGRP(206-214) sequence. |
| 287 | 20439719 | These mice developed islet inflammation and diabetes with normal incidence and kinetics, but their inflammatory lesions could recruit neither naive (endogenous or exogenous) nor ex vivo-activated IGRP(206-214)-reactive CD8(+) T cells. |
| 288 | 20439719 | Conversely, IGRP(206-214)-reactive, but not nonautoreactive CD8(+) T cells rapidly homed to and accumulated in the inflamed islets of wild-type NOD mice. |
| 289 | 21825122 | Most studies with class I pMHC multimers used noncovalently linked peptides, which can allow unwanted CD8(+) T-cell activation as a result of peptide transfer to cellular MHC molecules. |
| 290 | 21825122 | To circumvent this problem, and given the role of self-reactive CD8(+) T cells in the development of type 1 diabetes, we designed a single-chain pMHC complex (scK(d).IGRP) by using the class I MHC molecule H-2K(d) and a covalently linked peptide derived from islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP(206-214)), a well established autoantigen in NOD mice. |
| 291 | 21825122 | X-ray diffraction studies revealed that the peptide is presented in the groove of the MHC molecule in canonical fashion, and it was also demonstrated that scK(d).IGRP tetramers bound specifically to cognate CD8(+) T cells. |
| 292 | 21896930 | Deletion of the G6pc2 gene encoding the islet-specific glucose-6-phosphatase catalytic subunit-related protein does not affect the progression or incidence of type 1 diabetes in NOD/ShiLtJ mice. |
| 293 | 21990353 | Here, we document for the first time that CARHSP1 is regulated by nutrient status in the liver and functions at the transcriptional level to negatively regulate gluconeogenic genes, including the glucose-6-phosphatase catalytic subunit (G6Pc) and phosphoenolpyruvate carboxykinase 1 (PEPCK1). |
| 294 | 22069258 | T cells target various antigens such as insulin, chromogranin A, glutamic acid decarboxylase and islet-specific glucose-6-phosphatase catalytic subunit-related protein. |
| 295 | 22190647 | Transgenic NOD mice that overexpress islet-specific glucose 6 phosphatase catalytic subunit-related protein (IGRP) in antigen-presenting cells (NOD-IGRP mice) have no IGRP-specific T cells. |
| 296 | 22345013 | Among 36 T2DM associated genes tested, 19 genes (including G6PC, CCR2B, CTLA4) displayed a similar expression pattern in both spontaneous and diet-induced T2DM models and were significantly up-regulated or down-regulated compared to controls. |
| 297 | 22427377 | Nonobese diabetic RIP-IL35 transgenic mice exhibited decreased islet infiltration with substantial reductions in the number of CD4(+) and CD8(+) T cells, and frequency of glucose-6-phosphatase catalytic subunit-related protein-specific CD8(+) T cells. |
| 298 | 22549789 | Overexpression of ERRγ induced Pck1 and G6PC gene expression and glucose production in primary hepatocytes, whereas abolition of ERRγ gene expression attenuated forskolin-mediated induction of gluconeogenic gene expression. |
| 299 | 22549789 | Deletion and mutation analyses of the Pck1 promoter showed that ERRγ directly regulates the Pck1 gene transcription via ERR response elements of the Pck1 promoter as confirmed by ChIP assay and in vivo imaging analysis. |
| 300 | 22678909 | This effect was not associated with significant immune changes in islet infiltrates, either in terms of cell composition or frequency and IFN-γ secretion of islet-reactive CD8(+) T cells recognizing the immunodominant epitopes insulin B(15-23) and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)(206-214). |
| 301 | 22787137 | Glucotoxicity induces glucose-6-phosphatase catalytic unit expression by acting on the interaction of HIF-1α with CREB-binding protein. |
| 302 | 22787137 | The induction of G6pc promoter activity by glucose was eliminated in the presence of small interfering RNA, targeting either the hypoxia-inducible factor (HIF)-1α or the CREB-binding protein (CBP). |
| 303 | 22787137 | Glucose increased the interaction of HIF-1α with CBP and the recruitment of HIF-1 on the G6pc promoter. |
| 304 | 22787137 | This mechanism leading to the induction of HIF-1 transcriptional activity may contribute to the increase of hepatic glucose production during type 2 diabetes. |
| 305 | 22787137 | Glucotoxicity induces glucose-6-phosphatase catalytic unit expression by acting on the interaction of HIF-1α with CREB-binding protein. |
| 306 | 22787137 | The induction of G6pc promoter activity by glucose was eliminated in the presence of small interfering RNA, targeting either the hypoxia-inducible factor (HIF)-1α or the CREB-binding protein (CBP). |
| 307 | 22787137 | Glucose increased the interaction of HIF-1α with CBP and the recruitment of HIF-1 on the G6pc promoter. |
| 308 | 22787137 | This mechanism leading to the induction of HIF-1 transcriptional activity may contribute to the increase of hepatic glucose production during type 2 diabetes. |
| 309 | 22787137 | Glucotoxicity induces glucose-6-phosphatase catalytic unit expression by acting on the interaction of HIF-1α with CREB-binding protein. |
| 310 | 22787137 | The induction of G6pc promoter activity by glucose was eliminated in the presence of small interfering RNA, targeting either the hypoxia-inducible factor (HIF)-1α or the CREB-binding protein (CBP). |
| 311 | 22787137 | Glucose increased the interaction of HIF-1α with CBP and the recruitment of HIF-1 on the G6pc promoter. |
| 312 | 22787137 | This mechanism leading to the induction of HIF-1 transcriptional activity may contribute to the increase of hepatic glucose production during type 2 diabetes. |
| 313 | 22872234 | In addition to global liquid chromatography-tandem mass spectrometry analysis, the targeted approach of multiple-reaction monitoring was used to quantitate the immunodominant K(d)-restricted T-cell epitope islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)₂₀₆₋₂₁₄. |
| 314 | 22908330 | Autoantigen recognition is required for recruitment of IGRP(206-214)-autoreactive CD8+ T cells but is dispensable for tolerance. |
| 315 | 22908330 | Central and peripheral tolerance hinder the contribution of high-avidity clonotypes targeting residues 206-214 of islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP(206-214)) during the earliest stages of autoimmune diabetes. |
| 316 | 22908330 | In this study, we probe the molecular determinants and biochemical consequences of IGRP(206-214)/K(d) recognition by high-, intermediate-, and low-avidity autoreactive CD8+ T cells, and we investigate the effects of genetic IGRP(206-214) silencing on their developmental biology. |
| 317 | 22908330 | We find that differences in avidity for IGRP(206-214)/K(d) map to CDR1α and are associated with quantitative differences in CD3ε proline-rich sequence exposure and Nck recruitment. |
| 318 | 22908330 | Unexpectedly, we find that tolerance of high-avidity CD8+ T cells, unlike their activation and recruitment into the pancreas, is dissociated from recognition of IGRP(206-214), particularly in adult mice. |
| 319 | 22983906 | G6PC2, also known as islet-specific glucose 6-phosphatase catalytic subunit-related protein (IGRP), is a major target of autoreactive CD8(+) T cells in both diabetic human subjects and the non-obese diabetic (NOD) mouse. |
| 320 | 22983906 | However, in contrast to the abundant literature regarding the CD8(+) response to this antigen, much less is known about the potential involvement of IGRP-reactive CD4(+) T cells in diabetogenesis. |
| 321 | 22983906 | To address this issue, we immunized NOD mice with membranes from insect cells overexpressing full-length recombinant mouse IGRP and measured recall responses of purified CD4(+) T cells using a library of overlapping peptides encompassing the entire 355-aa primary sequence. |
| 322 | 23155466 | To address a destructive role for autoreactive CD8 T-cells in human disease, we assessed the pathogenicity of a CD8 T-cell clone derived from a T1D donor and specific for an HLA-A2-restricted epitope of islet-specific glucose-6-phosphatase catalytic-subunit related protein (IGRP). |
| 323 | 23155466 | HLA-A2/IGRP tetramer staining revealed a higher frequency of IGRP-specific CD8 T-cells in the peripheral blood of recent onset human individuals than of healthy donors. |
| 324 | 23155466 | IGRP(265-273)-specific CD8 T-cells that were cloned from the peripheral blood of a recent onset T1D individual were shown to secrete IFNγ and Granzyme B after antigen-specific activation and lyse HLA-A2-expressing murine islets in-vitro. |
| 325 | 23155466 | Using the HLA-A2 NOD-scid IL2rγ(null) mouse model, HLA-A2-restricted IGRP-specific CD8 T-cells induced a destructive insulitis. |
| 326 | 23160528 | We monitored the recruitment of islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)₂₀₆₋₂₁₄-reactive CD8⁺ T cells into IGRP₂₀₆₋₂₁₄-competent and IGRP₂₀₆₋₂₁₄-deficient islet grafts in diabetic wild-type or IGRP₂₀₆₋₂₁₄(-/-) nonobese diabetic hosts (harboring either naive and memory T cells or only naive IGRP₂₀₆₋₂₁₄-specific T-cells, respectively). |
| 327 | 23267038 | Specific reduction of G6PT may contribute to downregulation of hepatic 11β-HSD1 in diabetic mice. |
| 328 | 23267038 | Pre-receptor activation of glucocorticoids via 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 (HSD11B1)) has been identified as an important mediator of the metabolic syndrome. |
| 329 | 23267038 | Hexose-6-phosphate dehydrogenase (H6PDH) mediates 11β-HSD1 amplifying tissue glucocorticoid production by driving intracellular NADPH exposure to 11β-HSD1 and requires glucose-6-phosphate transporter (G6PT (SLC37A4)) to maintain its activity. |
| 330 | 23267038 | Here, we evaluated the possible role of G6PT antisense oligonucleotides (G6PT ASO) in the pre-receptor metabolism of glucocorticoids as related to glucose homeostasis and insulin tolerance by examining the production of 11β-HSD1 and H6PDH in both male db/+ and db/db mouse liver tissue. |
| 331 | 23267038 | We observed that G6PT ASO treatment of db/db mice markedly reduced hepatic G6PT mRNA and protein levels and substantially diminished the activation of hepatic 11β-HSD1 and H6PDH. |
| 332 | 23267038 | Reduction of G6pt expression was correlated with the suppression of both hepatic gluconeogenic enzymes G6Pase and PEPCK and corresponded to the improvement of hyperglycemia and insulin resistance in db/db mice. |
| 333 | 23267038 | Addition of G6PT ASO to mouse hepa1-6 cells led to a dose-dependent decrease in 11B-Hsd1 production. |
| 334 | 23267038 | Knockdown of G6PT with RNA interference also impaired 11B-Hsd1 expression and showed comparable effects to H6pdh siRNA on silencing of H6pdh and 11B-Hsd1 expression in these intact cells. |
| 335 | 23267038 | Specific reduction of G6PT may contribute to downregulation of hepatic 11β-HSD1 in diabetic mice. |
| 336 | 23267038 | Pre-receptor activation of glucocorticoids via 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 (HSD11B1)) has been identified as an important mediator of the metabolic syndrome. |
| 337 | 23267038 | Hexose-6-phosphate dehydrogenase (H6PDH) mediates 11β-HSD1 amplifying tissue glucocorticoid production by driving intracellular NADPH exposure to 11β-HSD1 and requires glucose-6-phosphate transporter (G6PT (SLC37A4)) to maintain its activity. |
| 338 | 23267038 | Here, we evaluated the possible role of G6PT antisense oligonucleotides (G6PT ASO) in the pre-receptor metabolism of glucocorticoids as related to glucose homeostasis and insulin tolerance by examining the production of 11β-HSD1 and H6PDH in both male db/+ and db/db mouse liver tissue. |
| 339 | 23267038 | We observed that G6PT ASO treatment of db/db mice markedly reduced hepatic G6PT mRNA and protein levels and substantially diminished the activation of hepatic 11β-HSD1 and H6PDH. |
| 340 | 23267038 | Reduction of G6pt expression was correlated with the suppression of both hepatic gluconeogenic enzymes G6Pase and PEPCK and corresponded to the improvement of hyperglycemia and insulin resistance in db/db mice. |
| 341 | 23267038 | Addition of G6PT ASO to mouse hepa1-6 cells led to a dose-dependent decrease in 11B-Hsd1 production. |
| 342 | 23267038 | Knockdown of G6PT with RNA interference also impaired 11B-Hsd1 expression and showed comparable effects to H6pdh siRNA on silencing of H6pdh and 11B-Hsd1 expression in these intact cells. |
| 343 | 23267038 | Specific reduction of G6PT may contribute to downregulation of hepatic 11β-HSD1 in diabetic mice. |
| 344 | 23267038 | Pre-receptor activation of glucocorticoids via 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 (HSD11B1)) has been identified as an important mediator of the metabolic syndrome. |
| 345 | 23267038 | Hexose-6-phosphate dehydrogenase (H6PDH) mediates 11β-HSD1 amplifying tissue glucocorticoid production by driving intracellular NADPH exposure to 11β-HSD1 and requires glucose-6-phosphate transporter (G6PT (SLC37A4)) to maintain its activity. |
| 346 | 23267038 | Here, we evaluated the possible role of G6PT antisense oligonucleotides (G6PT ASO) in the pre-receptor metabolism of glucocorticoids as related to glucose homeostasis and insulin tolerance by examining the production of 11β-HSD1 and H6PDH in both male db/+ and db/db mouse liver tissue. |
| 347 | 23267038 | We observed that G6PT ASO treatment of db/db mice markedly reduced hepatic G6PT mRNA and protein levels and substantially diminished the activation of hepatic 11β-HSD1 and H6PDH. |
| 348 | 23267038 | Reduction of G6pt expression was correlated with the suppression of both hepatic gluconeogenic enzymes G6Pase and PEPCK and corresponded to the improvement of hyperglycemia and insulin resistance in db/db mice. |
| 349 | 23267038 | Addition of G6PT ASO to mouse hepa1-6 cells led to a dose-dependent decrease in 11B-Hsd1 production. |
| 350 | 23267038 | Knockdown of G6PT with RNA interference also impaired 11B-Hsd1 expression and showed comparable effects to H6pdh siRNA on silencing of H6pdh and 11B-Hsd1 expression in these intact cells. |
| 351 | 23267038 | Specific reduction of G6PT may contribute to downregulation of hepatic 11β-HSD1 in diabetic mice. |
| 352 | 23267038 | Pre-receptor activation of glucocorticoids via 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 (HSD11B1)) has been identified as an important mediator of the metabolic syndrome. |
| 353 | 23267038 | Hexose-6-phosphate dehydrogenase (H6PDH) mediates 11β-HSD1 amplifying tissue glucocorticoid production by driving intracellular NADPH exposure to 11β-HSD1 and requires glucose-6-phosphate transporter (G6PT (SLC37A4)) to maintain its activity. |
| 354 | 23267038 | Here, we evaluated the possible role of G6PT antisense oligonucleotides (G6PT ASO) in the pre-receptor metabolism of glucocorticoids as related to glucose homeostasis and insulin tolerance by examining the production of 11β-HSD1 and H6PDH in both male db/+ and db/db mouse liver tissue. |
| 355 | 23267038 | We observed that G6PT ASO treatment of db/db mice markedly reduced hepatic G6PT mRNA and protein levels and substantially diminished the activation of hepatic 11β-HSD1 and H6PDH. |
| 356 | 23267038 | Reduction of G6pt expression was correlated with the suppression of both hepatic gluconeogenic enzymes G6Pase and PEPCK and corresponded to the improvement of hyperglycemia and insulin resistance in db/db mice. |
| 357 | 23267038 | Addition of G6PT ASO to mouse hepa1-6 cells led to a dose-dependent decrease in 11B-Hsd1 production. |
| 358 | 23267038 | Knockdown of G6PT with RNA interference also impaired 11B-Hsd1 expression and showed comparable effects to H6pdh siRNA on silencing of H6pdh and 11B-Hsd1 expression in these intact cells. |
| 359 | 23267038 | Specific reduction of G6PT may contribute to downregulation of hepatic 11β-HSD1 in diabetic mice. |
| 360 | 23267038 | Pre-receptor activation of glucocorticoids via 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 (HSD11B1)) has been identified as an important mediator of the metabolic syndrome. |
| 361 | 23267038 | Hexose-6-phosphate dehydrogenase (H6PDH) mediates 11β-HSD1 amplifying tissue glucocorticoid production by driving intracellular NADPH exposure to 11β-HSD1 and requires glucose-6-phosphate transporter (G6PT (SLC37A4)) to maintain its activity. |
| 362 | 23267038 | Here, we evaluated the possible role of G6PT antisense oligonucleotides (G6PT ASO) in the pre-receptor metabolism of glucocorticoids as related to glucose homeostasis and insulin tolerance by examining the production of 11β-HSD1 and H6PDH in both male db/+ and db/db mouse liver tissue. |
| 363 | 23267038 | We observed that G6PT ASO treatment of db/db mice markedly reduced hepatic G6PT mRNA and protein levels and substantially diminished the activation of hepatic 11β-HSD1 and H6PDH. |
| 364 | 23267038 | Reduction of G6pt expression was correlated with the suppression of both hepatic gluconeogenic enzymes G6Pase and PEPCK and corresponded to the improvement of hyperglycemia and insulin resistance in db/db mice. |
| 365 | 23267038 | Addition of G6PT ASO to mouse hepa1-6 cells led to a dose-dependent decrease in 11B-Hsd1 production. |
| 366 | 23267038 | Knockdown of G6PT with RNA interference also impaired 11B-Hsd1 expression and showed comparable effects to H6pdh siRNA on silencing of H6pdh and 11B-Hsd1 expression in these intact cells. |
| 367 | 23267038 | Specific reduction of G6PT may contribute to downregulation of hepatic 11β-HSD1 in diabetic mice. |
| 368 | 23267038 | Pre-receptor activation of glucocorticoids via 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 (HSD11B1)) has been identified as an important mediator of the metabolic syndrome. |
| 369 | 23267038 | Hexose-6-phosphate dehydrogenase (H6PDH) mediates 11β-HSD1 amplifying tissue glucocorticoid production by driving intracellular NADPH exposure to 11β-HSD1 and requires glucose-6-phosphate transporter (G6PT (SLC37A4)) to maintain its activity. |
| 370 | 23267038 | Here, we evaluated the possible role of G6PT antisense oligonucleotides (G6PT ASO) in the pre-receptor metabolism of glucocorticoids as related to glucose homeostasis and insulin tolerance by examining the production of 11β-HSD1 and H6PDH in both male db/+ and db/db mouse liver tissue. |
| 371 | 23267038 | We observed that G6PT ASO treatment of db/db mice markedly reduced hepatic G6PT mRNA and protein levels and substantially diminished the activation of hepatic 11β-HSD1 and H6PDH. |
| 372 | 23267038 | Reduction of G6pt expression was correlated with the suppression of both hepatic gluconeogenic enzymes G6Pase and PEPCK and corresponded to the improvement of hyperglycemia and insulin resistance in db/db mice. |
| 373 | 23267038 | Addition of G6PT ASO to mouse hepa1-6 cells led to a dose-dependent decrease in 11B-Hsd1 production. |
| 374 | 23267038 | Knockdown of G6PT with RNA interference also impaired 11B-Hsd1 expression and showed comparable effects to H6pdh siRNA on silencing of H6pdh and 11B-Hsd1 expression in these intact cells. |
| 375 | 23267038 | Specific reduction of G6PT may contribute to downregulation of hepatic 11β-HSD1 in diabetic mice. |
| 376 | 23267038 | Pre-receptor activation of glucocorticoids via 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 (HSD11B1)) has been identified as an important mediator of the metabolic syndrome. |
| 377 | 23267038 | Hexose-6-phosphate dehydrogenase (H6PDH) mediates 11β-HSD1 amplifying tissue glucocorticoid production by driving intracellular NADPH exposure to 11β-HSD1 and requires glucose-6-phosphate transporter (G6PT (SLC37A4)) to maintain its activity. |
| 378 | 23267038 | Here, we evaluated the possible role of G6PT antisense oligonucleotides (G6PT ASO) in the pre-receptor metabolism of glucocorticoids as related to glucose homeostasis and insulin tolerance by examining the production of 11β-HSD1 and H6PDH in both male db/+ and db/db mouse liver tissue. |
| 379 | 23267038 | We observed that G6PT ASO treatment of db/db mice markedly reduced hepatic G6PT mRNA and protein levels and substantially diminished the activation of hepatic 11β-HSD1 and H6PDH. |
| 380 | 23267038 | Reduction of G6pt expression was correlated with the suppression of both hepatic gluconeogenic enzymes G6Pase and PEPCK and corresponded to the improvement of hyperglycemia and insulin resistance in db/db mice. |
| 381 | 23267038 | Addition of G6PT ASO to mouse hepa1-6 cells led to a dose-dependent decrease in 11B-Hsd1 production. |
| 382 | 23267038 | Knockdown of G6PT with RNA interference also impaired 11B-Hsd1 expression and showed comparable effects to H6pdh siRNA on silencing of H6pdh and 11B-Hsd1 expression in these intact cells. |
| 383 | 23465595 | This study examined the role of TLR4 in mediating palmitate effects on the expression of phosphoenolpyruvate carboxykinase (PCK1) and the catalytic subunit of glucose-6-phosphatase (G6PC), rate-determining gluconeogenic enzymes. |
| 384 | 23465595 | Palmitate induced dose-dependent increases in PCK1 and G6PC mRNA abundance, which were prevented by the TLR4 decoy peptide. |
| 385 | 23465595 | Palmitate doubled PCK1 promoter activity, and TLR4 knockdown ablated this response. |
| 386 | 23465595 | Lipopolysaccharide and monophosphoryl lipid A also up-regulated G6PC and PCK1 transcript abundance in a TLR4-dependent manner. |
| 387 | 23465595 | Addition of oleate attenuated palmitate-induced increases in G6PC and PCK1 mRNA abundance. |
| 388 | 23465595 | Palmitate increased nuclear factor κ-light-chain-enhancer of activated B cells reporter gene activity, which was unaffected by TLR4 blockade, but increased mRNA abundance of hepatocyte-specific cyclic AMP response element binding protein, a transcriptional regulator of PCK1, in a TLR4-dependent manner. |
| 389 | 23465595 | Finally, TLR4 activation by palmitate increased subsequent cellular uptake of palmitate, and inhibiting ceramide synthesis ablated palmitate effects on PCK1 mRNA abundance and promoter activity. |
| 390 | 23465595 | This study examined the role of TLR4 in mediating palmitate effects on the expression of phosphoenolpyruvate carboxykinase (PCK1) and the catalytic subunit of glucose-6-phosphatase (G6PC), rate-determining gluconeogenic enzymes. |
| 391 | 23465595 | Palmitate induced dose-dependent increases in PCK1 and G6PC mRNA abundance, which were prevented by the TLR4 decoy peptide. |
| 392 | 23465595 | Palmitate doubled PCK1 promoter activity, and TLR4 knockdown ablated this response. |
| 393 | 23465595 | Lipopolysaccharide and monophosphoryl lipid A also up-regulated G6PC and PCK1 transcript abundance in a TLR4-dependent manner. |
| 394 | 23465595 | Addition of oleate attenuated palmitate-induced increases in G6PC and PCK1 mRNA abundance. |
| 395 | 23465595 | Palmitate increased nuclear factor κ-light-chain-enhancer of activated B cells reporter gene activity, which was unaffected by TLR4 blockade, but increased mRNA abundance of hepatocyte-specific cyclic AMP response element binding protein, a transcriptional regulator of PCK1, in a TLR4-dependent manner. |
| 396 | 23465595 | Finally, TLR4 activation by palmitate increased subsequent cellular uptake of palmitate, and inhibiting ceramide synthesis ablated palmitate effects on PCK1 mRNA abundance and promoter activity. |
| 397 | 23465595 | This study examined the role of TLR4 in mediating palmitate effects on the expression of phosphoenolpyruvate carboxykinase (PCK1) and the catalytic subunit of glucose-6-phosphatase (G6PC), rate-determining gluconeogenic enzymes. |
| 398 | 23465595 | Palmitate induced dose-dependent increases in PCK1 and G6PC mRNA abundance, which were prevented by the TLR4 decoy peptide. |
| 399 | 23465595 | Palmitate doubled PCK1 promoter activity, and TLR4 knockdown ablated this response. |
| 400 | 23465595 | Lipopolysaccharide and monophosphoryl lipid A also up-regulated G6PC and PCK1 transcript abundance in a TLR4-dependent manner. |
| 401 | 23465595 | Addition of oleate attenuated palmitate-induced increases in G6PC and PCK1 mRNA abundance. |
| 402 | 23465595 | Palmitate increased nuclear factor κ-light-chain-enhancer of activated B cells reporter gene activity, which was unaffected by TLR4 blockade, but increased mRNA abundance of hepatocyte-specific cyclic AMP response element binding protein, a transcriptional regulator of PCK1, in a TLR4-dependent manner. |
| 403 | 23465595 | Finally, TLR4 activation by palmitate increased subsequent cellular uptake of palmitate, and inhibiting ceramide synthesis ablated palmitate effects on PCK1 mRNA abundance and promoter activity. |
| 404 | 23465595 | This study examined the role of TLR4 in mediating palmitate effects on the expression of phosphoenolpyruvate carboxykinase (PCK1) and the catalytic subunit of glucose-6-phosphatase (G6PC), rate-determining gluconeogenic enzymes. |
| 405 | 23465595 | Palmitate induced dose-dependent increases in PCK1 and G6PC mRNA abundance, which were prevented by the TLR4 decoy peptide. |
| 406 | 23465595 | Palmitate doubled PCK1 promoter activity, and TLR4 knockdown ablated this response. |
| 407 | 23465595 | Lipopolysaccharide and monophosphoryl lipid A also up-regulated G6PC and PCK1 transcript abundance in a TLR4-dependent manner. |
| 408 | 23465595 | Addition of oleate attenuated palmitate-induced increases in G6PC and PCK1 mRNA abundance. |
| 409 | 23465595 | Palmitate increased nuclear factor κ-light-chain-enhancer of activated B cells reporter gene activity, which was unaffected by TLR4 blockade, but increased mRNA abundance of hepatocyte-specific cyclic AMP response element binding protein, a transcriptional regulator of PCK1, in a TLR4-dependent manner. |
| 410 | 23465595 | Finally, TLR4 activation by palmitate increased subsequent cellular uptake of palmitate, and inhibiting ceramide synthesis ablated palmitate effects on PCK1 mRNA abundance and promoter activity. |
| 411 | 23743798 | Liver glucose-6-phosphatase proteins in suckling and weaned grey seal pups: structural similarities to other mammals and relationship to nutrition, insulin signalling and metabolite levels. |
| 412 | 23743798 | G6Pase comprises a translocase (SLC37A4) and a catalytic subunit (G6PC). |
| 413 | 23743798 | G6PC and SLC37A4 expression and activity are normally regulated by nutritional state and glucostatic hormones, particularly insulin, and are elevated in diabetes. |
| 414 | 23743798 | We tested the hypotheses that (1) grey seal G6PC and SLC37A4 cDNA and predicted protein sequences differ from other species' at functional sites, (2) relative G6Pase protein abundances are lower during feeding than fasting and (3) relative G6Pase protein abundances are related to insulin, insulin receptor phosphorylation and key metabolite levels. |
| 415 | 23743798 | We show that G6PC and partial SLC37A4 cDNA sequences encode proteins sharing 82-95 % identity with other mammals. |
| 416 | 23743798 | Liver glucose-6-phosphatase proteins in suckling and weaned grey seal pups: structural similarities to other mammals and relationship to nutrition, insulin signalling and metabolite levels. |
| 417 | 23743798 | G6Pase comprises a translocase (SLC37A4) and a catalytic subunit (G6PC). |
| 418 | 23743798 | G6PC and SLC37A4 expression and activity are normally regulated by nutritional state and glucostatic hormones, particularly insulin, and are elevated in diabetes. |
| 419 | 23743798 | We tested the hypotheses that (1) grey seal G6PC and SLC37A4 cDNA and predicted protein sequences differ from other species' at functional sites, (2) relative G6Pase protein abundances are lower during feeding than fasting and (3) relative G6Pase protein abundances are related to insulin, insulin receptor phosphorylation and key metabolite levels. |
| 420 | 23743798 | We show that G6PC and partial SLC37A4 cDNA sequences encode proteins sharing 82-95 % identity with other mammals. |
| 421 | 23743798 | Liver glucose-6-phosphatase proteins in suckling and weaned grey seal pups: structural similarities to other mammals and relationship to nutrition, insulin signalling and metabolite levels. |
| 422 | 23743798 | G6Pase comprises a translocase (SLC37A4) and a catalytic subunit (G6PC). |
| 423 | 23743798 | G6PC and SLC37A4 expression and activity are normally regulated by nutritional state and glucostatic hormones, particularly insulin, and are elevated in diabetes. |
| 424 | 23743798 | We tested the hypotheses that (1) grey seal G6PC and SLC37A4 cDNA and predicted protein sequences differ from other species' at functional sites, (2) relative G6Pase protein abundances are lower during feeding than fasting and (3) relative G6Pase protein abundances are related to insulin, insulin receptor phosphorylation and key metabolite levels. |
| 425 | 23743798 | We show that G6PC and partial SLC37A4 cDNA sequences encode proteins sharing 82-95 % identity with other mammals. |
| 426 | 23743798 | Liver glucose-6-phosphatase proteins in suckling and weaned grey seal pups: structural similarities to other mammals and relationship to nutrition, insulin signalling and metabolite levels. |
| 427 | 23743798 | G6Pase comprises a translocase (SLC37A4) and a catalytic subunit (G6PC). |
| 428 | 23743798 | G6PC and SLC37A4 expression and activity are normally regulated by nutritional state and glucostatic hormones, particularly insulin, and are elevated in diabetes. |
| 429 | 23743798 | We tested the hypotheses that (1) grey seal G6PC and SLC37A4 cDNA and predicted protein sequences differ from other species' at functional sites, (2) relative G6Pase protein abundances are lower during feeding than fasting and (3) relative G6Pase protein abundances are related to insulin, insulin receptor phosphorylation and key metabolite levels. |
| 430 | 23743798 | We show that G6PC and partial SLC37A4 cDNA sequences encode proteins sharing 82-95 % identity with other mammals. |
| 431 | 23835330 | IT repressed the liver expression of glucose-6-phosphatase (G6PC) and phosphoenolpyruvate carboxykinase (Pepck), two gluconeogenetic genes, along with the expression of LXRα and its target genes sterol regulatory element-binding protein (Srebp) 1c and fatty acid synthase (Fas) in the liver. |
| 432 | 23990360 | In morbidly obese patients undergoing bariatric surgery, we show that Notch activation positively correlates with glucose-6-phosphatase (G6PC) and phosphoenolpyruvate carboxykinase (PCK1) expression, key regulators of hepatic glucose output. |