Ignet

Gene Information

Gene symbol: G6PC2

Gene name: glucose-6-phosphatase, catalytic, 2

HGNC ID: 28906

Synonyms: IGRP

Related Genes

#	Gene Symbol	Number of hits
1	ABCB11	1 hits
2	ABCC8	1 hits
3	ADRA2A	1 hits
4	APLP2	1 hits
5	CAT	1 hits
6	CD4	1 hits
7	CD8A	1 hits
8	CDKAL1	1 hits
9	CHGA	1 hits
10	CPE	1 hits
11	CXCR3	1 hits
12	DGKB	1 hits
13	FOXA1	1 hits
14	FOXA2	1 hits
15	G6PC	1 hits
16	G6PC3	1 hits
17	GAD1	1 hits
18	GAD2	1 hits
19	GATA4	1 hits
20	GCK	1 hits
21	GCKR	1 hits
22	GFAP	1 hits
23	GZMB	1 hits
24	HHEX	1 hits
25	HK1	1 hits
26	HLA-A	1 hits
27	HNF1B	1 hits
28	HSPD1	1 hits
29	IAPP	1 hits
30	IFNG	1 hits
31	IGF1	1 hits
32	IL10	1 hits
33	INS	1 hits
34	IRS1	1 hits
35	ISL1	1 hits
36	KCNJ11	1 hits
37	MAFA	1 hits
38	MICB	1 hits
39	MTNR1B	1 hits
40	NCK1	1 hits
41	NEUROD1	1 hits
42	PAX6	1 hits
43	PDX1	1 hits
44	PTF1A	1 hits
45	PTPRN	1 hits
46	PTPRN2	1 hits
47	SLC2A2	1 hits
48	SLC30A8	1 hits
49	SLC37A4	1 hits
50	TCF7L2	1 hits

Related Sentences

#	PMID	Sentence
1	10078553	Molecular cloning of a pancreatic islet-specific glucose-6-phosphatase catalytic subunit-related protein.
2	10078553	A pancreatic islet-specific glucose-6-phosphatase-related protein (IGRP) was cloned using a subtractive cDNA expression cloning procedure from mouse insulinoma tissue.
3	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.
4	10078553	Molecular cloning of a pancreatic islet-specific glucose-6-phosphatase catalytic subunit-related protein.
5	10078553	A pancreatic islet-specific glucose-6-phosphatase-related protein (IGRP) was cloned using a subtractive cDNA expression cloning procedure from mouse insulinoma tissue.
6	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.
7	10078553	Molecular cloning of a pancreatic islet-specific glucose-6-phosphatase catalytic subunit-related protein.
8	10078553	A pancreatic islet-specific glucose-6-phosphatase-related protein (IGRP) was cloned using a subtractive cDNA expression cloning procedure from mouse insulinoma tissue.
9	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.
10	10078554	Structure and promoter activity of an islet-specific glucose-6-phosphatase catalytic subunit-related gene.
11	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).
12	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.
13	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.
14	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.
15	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.
16	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.
17	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.
18	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.
19	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.
20	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.
21	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).
22	14722102	Enzymatic characterization of the pancreatic islet-specific glucose-6-phosphatase-related protein (IGRP).
23	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.
24	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.
25	14722102	IGRP inhibitors may be an attractive new approach for the treatment of insulin secretion defects in type 2 diabetes.
26	14722102	Enzymatic characterization of the pancreatic islet-specific glucose-6-phosphatase-related protein (IGRP).
27	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.
28	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.
29	14722102	IGRP inhibitors may be an attractive new approach for the treatment of insulin secretion defects in type 2 diabetes.
30	14722102	Enzymatic characterization of the pancreatic islet-specific glucose-6-phosphatase-related protein (IGRP).
31	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.
32	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.
33	14722102	IGRP inhibitors may be an attractive new approach for the treatment of insulin secretion defects in type 2 diabetes.
34	14722102	Enzymatic characterization of the pancreatic islet-specific glucose-6-phosphatase-related protein (IGRP).
35	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.
36	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.
37	14722102	IGRP inhibitors may be an attractive new approach for the treatment of insulin secretion defects in type 2 diabetes.
38	15044018	The islet-specific glucose-6-phosphatase-related protein, implicated in diabetes, is a glycoprotein embedded in the endoplasmic reticulum membrane.
39	15044018	The islet-specific glucose-6-phosphatase-related protein (IGRP) has no known catalytic activity, but is of interest because it is the source of the peptide autoantigen targeted by a prevalent population of pathogenic CD8(+) T cells in non-obese diabetic mice.
40	15044018	The islet-specific glucose-6-phosphatase-related protein, implicated in diabetes, is a glycoprotein embedded in the endoplasmic reticulum membrane.
41	15044018	The islet-specific glucose-6-phosphatase-related protein (IGRP) has no known catalytic activity, but is of interest because it is the source of the peptide autoantigen targeted by a prevalent population of pathogenic CD8(+) T cells in non-obese diabetic mice.
42	15180990	Differential regulation of islet-specific glucose-6-phosphatase catalytic subunit-related protein gene transcription by Pax-6 and Pdx-1.
43	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.
44	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.
45	15180990	Additional experiments revealed a second non-consensus Pax-6 binding site in the -306/-274 IGRP promoter region.
46	15180990	Gel retardation assays revealed that another islet-enriched transcription factor, namely Pdx-1, binds four non-consensus elements in the IGRP promoter.
47	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.
48	15180990	Differential regulation of islet-specific glucose-6-phosphatase catalytic subunit-related protein gene transcription by Pax-6 and Pdx-1.
49	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.
50	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.
51	15180990	Additional experiments revealed a second non-consensus Pax-6 binding site in the -306/-274 IGRP promoter region.
52	15180990	Gel retardation assays revealed that another islet-enriched transcription factor, namely Pdx-1, binds four non-consensus elements in the IGRP promoter.
53	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.
54	15180990	Differential regulation of islet-specific glucose-6-phosphatase catalytic subunit-related protein gene transcription by Pax-6 and Pdx-1.
55	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.
56	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.
57	15180990	Additional experiments revealed a second non-consensus Pax-6 binding site in the -306/-274 IGRP promoter region.
58	15180990	Gel retardation assays revealed that another islet-enriched transcription factor, namely Pdx-1, binds four non-consensus elements in the IGRP promoter.
59	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.
60	15180990	Differential regulation of islet-specific glucose-6-phosphatase catalytic subunit-related protein gene transcription by Pax-6 and Pdx-1.
61	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.
62	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.
63	15180990	Additional experiments revealed a second non-consensus Pax-6 binding site in the -306/-274 IGRP promoter region.
64	15180990	Gel retardation assays revealed that another islet-enriched transcription factor, namely Pdx-1, binds four non-consensus elements in the IGRP promoter.
65	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.
66	15180990	Differential regulation of islet-specific glucose-6-phosphatase catalytic subunit-related protein gene transcription by Pax-6 and Pdx-1.
67	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.
68	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.
69	15180990	Additional experiments revealed a second non-consensus Pax-6 binding site in the -306/-274 IGRP promoter region.
70	15180990	Gel retardation assays revealed that another islet-enriched transcription factor, namely Pdx-1, binds four non-consensus elements in the IGRP promoter.
71	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.
72	15180990	Differential regulation of islet-specific glucose-6-phosphatase catalytic subunit-related protein gene transcription by Pax-6 and Pdx-1.
73	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.
74	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.
75	15180990	Additional experiments revealed a second non-consensus Pax-6 binding site in the -306/-274 IGRP promoter region.
76	15180990	Gel retardation assays revealed that another islet-enriched transcription factor, namely Pdx-1, binds four non-consensus elements in the IGRP promoter.
77	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.
78	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.
79	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.
80	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.
81	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.
82	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.
83	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.
84	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.
85	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.
86	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.
87	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.
88	15557165	Spontaneous autoimmune diabetes development in NOD mice requires both CD8(+) and CD4(+) T cells.
89	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.
90	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.
91	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.
92	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.
93	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.
94	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.
95	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.
96	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.
97	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.
98	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.
99	15843527	This study was undertaken to identify MHC class II-specific CD4(+) T cell epitopes of IGRP.
100	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.
101	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.
102	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.
103	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.
104	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.
105	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.
106	15843527	This study was undertaken to identify MHC class II-specific CD4(+) T cell epitopes of IGRP.
107	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.
108	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.
109	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.
110	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.
111	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.
112	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.
113	15843527	This study was undertaken to identify MHC class II-specific CD4(+) T cell epitopes of IGRP.
114	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.
115	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.
116	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.
117	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.
118	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.
119	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.
120	15843527	This study was undertaken to identify MHC class II-specific CD4(+) T cell epitopes of IGRP.
121	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.
122	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.
123	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.
124	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.
125	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.
126	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.
127	15843527	This study was undertaken to identify MHC class II-specific CD4(+) T cell epitopes of IGRP.
128	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.
129	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.
130	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.
131	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.
132	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.
133	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.
134	15843527	This study was undertaken to identify MHC class II-specific CD4(+) T cell epitopes of IGRP.
135	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.
136	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.
137	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.
138	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.
139	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.
140	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.
141	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.
142	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.
143	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.
144	16012821	In islet-specific glucose-6-phosphatase-related protein, the beta cell antigenic sequence that is targeted in diabetes is not responsible for the loss of phosphohydrolase activity.
145	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).
146	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.
147	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.
148	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.
149	16424193	Early autoimmune destruction of islet grafts is associated with a restricted repertoire of IGRP-specific CD8+ T cells in diabetic nonobese diabetic mice.
150	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.
151	16424193	Early autoimmune destruction of islet grafts is associated with a restricted repertoire of IGRP-specific CD8+ T cells in diabetic nonobese diabetic mice.
152	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.
153	16493034	Islet-specific glucose-6-phosphatase catalytic subunit-related protein-reactive CD4+ T cells in human subjects.
154	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.
155	16493034	This study was undertaken to examine CD4+ T cell responses toward IGRP in human subjects.
156	16493034	The tetramer-guided epitope mapping approach was used to identify IGRP-specific CD4+ T cell epitopes.
157	16493034	More than 80% of subjects with either DRB10401 or DRB10301 haplotype have IGRP-specific CD4+ T cell responses for at least one IGRP epitope.
158	16493034	IGRP-specific T cells from both healthy and T1D groups produce both gamma-IFN and IL-10.
159	16493034	DRA10101/DRB10401 IGRP(247-259)-restricted T cells also show cross-reactivity to an epitope derived from liver/kidney glucose-6-phosphatase.
160	16493034	Islet-specific glucose-6-phosphatase catalytic subunit-related protein-reactive CD4+ T cells in human subjects.
161	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.
162	16493034	This study was undertaken to examine CD4+ T cell responses toward IGRP in human subjects.
163	16493034	The tetramer-guided epitope mapping approach was used to identify IGRP-specific CD4+ T cell epitopes.
164	16493034	More than 80% of subjects with either DRB10401 or DRB10301 haplotype have IGRP-specific CD4+ T cell responses for at least one IGRP epitope.
165	16493034	IGRP-specific T cells from both healthy and T1D groups produce both gamma-IFN and IL-10.
166	16493034	DRA10101/DRB10401 IGRP(247-259)-restricted T cells also show cross-reactivity to an epitope derived from liver/kidney glucose-6-phosphatase.
167	16493034	Islet-specific glucose-6-phosphatase catalytic subunit-related protein-reactive CD4+ T cells in human subjects.
168	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.
169	16493034	This study was undertaken to examine CD4+ T cell responses toward IGRP in human subjects.
170	16493034	The tetramer-guided epitope mapping approach was used to identify IGRP-specific CD4+ T cell epitopes.
171	16493034	More than 80% of subjects with either DRB10401 or DRB10301 haplotype have IGRP-specific CD4+ T cell responses for at least one IGRP epitope.
172	16493034	IGRP-specific T cells from both healthy and T1D groups produce both gamma-IFN and IL-10.
173	16493034	DRA10101/DRB10401 IGRP(247-259)-restricted T cells also show cross-reactivity to an epitope derived from liver/kidney glucose-6-phosphatase.
174	16493034	Islet-specific glucose-6-phosphatase catalytic subunit-related protein-reactive CD4+ T cells in human subjects.
175	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.
176	16493034	This study was undertaken to examine CD4+ T cell responses toward IGRP in human subjects.
177	16493034	The tetramer-guided epitope mapping approach was used to identify IGRP-specific CD4+ T cell epitopes.
178	16493034	More than 80% of subjects with either DRB10401 or DRB10301 haplotype have IGRP-specific CD4+ T cell responses for at least one IGRP epitope.
179	16493034	IGRP-specific T cells from both healthy and T1D groups produce both gamma-IFN and IL-10.
180	16493034	DRA10101/DRB10401 IGRP(247-259)-restricted T cells also show cross-reactivity to an epitope derived from liver/kidney glucose-6-phosphatase.
181	16493034	Islet-specific glucose-6-phosphatase catalytic subunit-related protein-reactive CD4+ T cells in human subjects.
182	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.
183	16493034	This study was undertaken to examine CD4+ T cell responses toward IGRP in human subjects.
184	16493034	The tetramer-guided epitope mapping approach was used to identify IGRP-specific CD4+ T cell epitopes.
185	16493034	More than 80% of subjects with either DRB10401 or DRB10301 haplotype have IGRP-specific CD4+ T cell responses for at least one IGRP epitope.
186	16493034	IGRP-specific T cells from both healthy and T1D groups produce both gamma-IFN and IL-10.
187	16493034	DRA10101/DRB10401 IGRP(247-259)-restricted T cells also show cross-reactivity to an epitope derived from liver/kidney glucose-6-phosphatase.
188	16493034	Islet-specific glucose-6-phosphatase catalytic subunit-related protein-reactive CD4+ T cells in human subjects.
189	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.
190	16493034	This study was undertaken to examine CD4+ T cell responses toward IGRP in human subjects.
191	16493034	The tetramer-guided epitope mapping approach was used to identify IGRP-specific CD4+ T cell epitopes.
192	16493034	More than 80% of subjects with either DRB10401 or DRB10301 haplotype have IGRP-specific CD4+ T cell responses for at least one IGRP epitope.
193	16493034	IGRP-specific T cells from both healthy and T1D groups produce both gamma-IFN and IL-10.
194	16493034	DRA10101/DRB10401 IGRP(247-259)-restricted T cells also show cross-reactivity to an epitope derived from liver/kidney glucose-6-phosphatase.
195	16493034	Islet-specific glucose-6-phosphatase catalytic subunit-related protein-reactive CD4+ T cells in human subjects.
196	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.
197	16493034	This study was undertaken to examine CD4+ T cell responses toward IGRP in human subjects.
198	16493034	The tetramer-guided epitope mapping approach was used to identify IGRP-specific CD4+ T cell epitopes.
199	16493034	More than 80% of subjects with either DRB10401 or DRB10301 haplotype have IGRP-specific CD4+ T cell responses for at least one IGRP epitope.
200	16493034	IGRP-specific T cells from both healthy and T1D groups produce both gamma-IFN and IL-10.
201	16493034	DRA10101/DRB10401 IGRP(247-259)-restricted T cells also show cross-reactivity to an epitope derived from liver/kidney glucose-6-phosphatase.
202	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).
203	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.
204	16493087	CD8+ T cells from the transgenic mice are cytotoxic to murine and human HLA-A*0201-positive islet cells.
205	16493087	Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) is one of several important T1D autoantigens in standard NOD mice.
206	16493087	Three IGRP-derived peptides were identified as targets of diabetogenic HLA-A*0201-restricted T cells in our NOD transgenic stock.
207	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).
208	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.
209	16493087	CD8+ T cells from the transgenic mice are cytotoxic to murine and human HLA-A*0201-positive islet cells.
210	16493087	Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) is one of several important T1D autoantigens in standard NOD mice.
211	16493087	Three IGRP-derived peptides were identified as targets of diabetogenic HLA-A*0201-restricted T cells in our NOD transgenic stock.
212	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.
213	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).
214	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.
215	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.
216	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.
217	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.
218	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.
219	17065343	Other peptides recognized by type 1 diabetic or antibody-positive subjects included GFAP(143-151), IGRP(152-160), and GFAP(214-222).
220	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.
221	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.
222	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.
223	17065343	Other peptides recognized by type 1 diabetic or antibody-positive subjects included GFAP(143-151), IGRP(152-160), and GFAP(214-222).
224	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.
225	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.
226	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.
227	17065343	Other peptides recognized by type 1 diabetic or antibody-positive subjects included GFAP(143-151), IGRP(152-160), and GFAP(214-222).
228	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.
229	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.
230	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.
231	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).
232	17143333	Responses against islet antigens in NOD mice are prevented by tolerance to proinsulin but not IGRP.
233	17143333	T cells specific for proinsulin and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) can induce T1D in NOD mice.
234	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.
235	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.
236	17143333	Our results suggest that pathogenic proinsulin-specific immunity in NOD mice subsequently spreads to other antigens such as IGRP.
237	17143333	Responses against islet antigens in NOD mice are prevented by tolerance to proinsulin but not IGRP.
238	17143333	T cells specific for proinsulin and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) can induce T1D in NOD mice.
239	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.
240	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.
241	17143333	Our results suggest that pathogenic proinsulin-specific immunity in NOD mice subsequently spreads to other antigens such as IGRP.
242	17143333	Responses against islet antigens in NOD mice are prevented by tolerance to proinsulin but not IGRP.
243	17143333	T cells specific for proinsulin and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) can induce T1D in NOD mice.
244	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.
245	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.
246	17143333	Our results suggest that pathogenic proinsulin-specific immunity in NOD mice subsequently spreads to other antigens such as IGRP.
247	17143333	Responses against islet antigens in NOD mice are prevented by tolerance to proinsulin but not IGRP.
248	17143333	T cells specific for proinsulin and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) can induce T1D in NOD mice.
249	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.
250	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.
251	17143333	Our results suggest that pathogenic proinsulin-specific immunity in NOD mice subsequently spreads to other antigens such as IGRP.
252	17143333	Responses against islet antigens in NOD mice are prevented by tolerance to proinsulin but not IGRP.
253	17143333	T cells specific for proinsulin and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) can induce T1D in NOD mice.
254	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.
255	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.
256	17143333	Our results suggest that pathogenic proinsulin-specific immunity in NOD mice subsequently spreads to other antigens such as IGRP.
257	17265032	Deletion of the gene encoding the islet-specific glucose-6-phosphatase catalytic subunit-related protein autoantigen results in a mild metabolic phenotype.
258	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.
259	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.
260	17376821	Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) is an important antigenic target of diabetogenic CD8 cells in standard NOD mice.
261	17376840	Human clonal CD8 autoreactivity to an IGRP islet epitope shared between mice and men.
262	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.
263	17376840	We isolated a human CD8 T cell clone against this epitope, which confirms that this IGRP epitope is shared across species.
264	17376840	Human clonal CD8 autoreactivity to an IGRP islet epitope shared between mice and men.
265	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.
266	17376840	We isolated a human CD8 T cell clone against this epitope, which confirms that this IGRP epitope is shared across species.
267	17376840	Human clonal CD8 autoreactivity to an IGRP islet epitope shared between mice and men.
268	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.
269	17376840	We isolated a human CD8 T cell clone against this epitope, which confirms that this IGRP epitope is shared across species.
270	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.
271	17395746	Interestingly, and in contrast to nucleoprotein-specific CD8 T-cells, IGRP-specific T-cells showed increased CXCR3 expression.
272	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.
273	17395746	Interestingly, and in contrast to nucleoprotein-specific CD8 T-cells, IGRP-specific T-cells showed increased CXCR3 expression.
274	17565413	Endoplasmic reticulum stress caused by overexpression of islet-specific glucose-6-phosphatase catalytic subunit-related protein in pancreatic Beta-cells.
275	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.
276	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.
277	17565413	Endoplasmic reticulum stress caused by overexpression of islet-specific glucose-6-phosphatase catalytic subunit-related protein in pancreatic Beta-cells.
278	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.
279	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.
280	17565413	Endoplasmic reticulum stress caused by overexpression of islet-specific glucose-6-phosphatase catalytic subunit-related protein in pancreatic Beta-cells.
281	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.
282	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.
283	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.
284	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).
285	18354167	Autoimmunity to both proinsulin and IGRP is required for diabetes in nonobese diabetic 8.3 TCR transgenic mice.
286	18354167	T cells specific for proinsulin and islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP) induce diabetes in nonobese diabetic (NOD) mice.
287	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.
288	18354167	We previously showed that immune responses against proinsulin are necessary for IGRP(206-214)-specific CD8(+) T cells to expand.
289	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.
290	18354167	This suggests that islet inflammation can substitute for proinsulin-specific CD4(+) T cell help to activate IGRP(206-214)-specific T cells.
291	18354167	Autoimmunity to both proinsulin and IGRP is required for diabetes in nonobese diabetic 8.3 TCR transgenic mice.
292	18354167	T cells specific for proinsulin and islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP) induce diabetes in nonobese diabetic (NOD) mice.
293	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.
294	18354167	We previously showed that immune responses against proinsulin are necessary for IGRP(206-214)-specific CD8(+) T cells to expand.
295	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.
296	18354167	This suggests that islet inflammation can substitute for proinsulin-specific CD4(+) T cell help to activate IGRP(206-214)-specific T cells.
297	18354167	Autoimmunity to both proinsulin and IGRP is required for diabetes in nonobese diabetic 8.3 TCR transgenic mice.
298	18354167	T cells specific for proinsulin and islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP) induce diabetes in nonobese diabetic (NOD) mice.
299	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.
300	18354167	We previously showed that immune responses against proinsulin are necessary for IGRP(206-214)-specific CD8(+) T cells to expand.
301	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.
302	18354167	This suggests that islet inflammation can substitute for proinsulin-specific CD4(+) T cell help to activate IGRP(206-214)-specific T cells.
303	18354167	Autoimmunity to both proinsulin and IGRP is required for diabetes in nonobese diabetic 8.3 TCR transgenic mice.
304	18354167	T cells specific for proinsulin and islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP) induce diabetes in nonobese diabetic (NOD) mice.
305	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.
306	18354167	We previously showed that immune responses against proinsulin are necessary for IGRP(206-214)-specific CD8(+) T cells to expand.
307	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.
308	18354167	This suggests that islet inflammation can substitute for proinsulin-specific CD4(+) T cell help to activate IGRP(206-214)-specific T cells.
309	18354167	Autoimmunity to both proinsulin and IGRP is required for diabetes in nonobese diabetic 8.3 TCR transgenic mice.
310	18354167	T cells specific for proinsulin and islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP) induce diabetes in nonobese diabetic (NOD) mice.
311	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.
312	18354167	We previously showed that immune responses against proinsulin are necessary for IGRP(206-214)-specific CD8(+) T cells to expand.
313	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.
314	18354167	This suggests that islet inflammation can substitute for proinsulin-specific CD4(+) T cell help to activate IGRP(206-214)-specific T cells.
315	18354167	Autoimmunity to both proinsulin and IGRP is required for diabetes in nonobese diabetic 8.3 TCR transgenic mice.
316	18354167	T cells specific for proinsulin and islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP) induce diabetes in nonobese diabetic (NOD) mice.
317	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.
318	18354167	We previously showed that immune responses against proinsulin are necessary for IGRP(206-214)-specific CD8(+) T cells to expand.
319	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.
320	18354167	This suggests that islet inflammation can substitute for proinsulin-specific CD4(+) T cell help to activate IGRP(206-214)-specific T cells.
321	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.
322	18451265	We speculate that G6PC2 regulates FPG by modulating the set point for glucose-stimulated insulin secretion in pancreatic beta cells.
323	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.
324	18451265	We speculate that G6PC2 regulates FPG by modulating the set point for glucose-stimulated insulin secretion in pancreatic beta cells.
325	18521185	Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels.
326	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).
327	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.
328	18521185	Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels.
329	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).
330	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.
331	18521185	Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels.
332	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).
333	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.
334	18753309	Foxa2 and MafA regulate islet-specific glucose-6-phosphatase catalytic subunit-related protein gene expression.
335	18753309	Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP/G6PC2) is a major autoantigen in both mouse and human type 1 diabetes.
336	18753309	Chromatin immunoprecipitation (ChIP) assays have shown that the IGRP promoter binds the islet-enriched transcription factors Pax-6 and BETA2.
337	18753309	We show here, again using ChIP assays, that the IGRP promoter also binds the islet-enriched transcription factors MafA and Foxa2.
338	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.
339	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.
340	18753309	Foxa2 and MafA regulate islet-specific glucose-6-phosphatase catalytic subunit-related protein gene expression.
341	18753309	Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP/G6PC2) is a major autoantigen in both mouse and human type 1 diabetes.
342	18753309	Chromatin immunoprecipitation (ChIP) assays have shown that the IGRP promoter binds the islet-enriched transcription factors Pax-6 and BETA2.
343	18753309	We show here, again using ChIP assays, that the IGRP promoter also binds the islet-enriched transcription factors MafA and Foxa2.
344	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.
345	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.
346	18753309	Foxa2 and MafA regulate islet-specific glucose-6-phosphatase catalytic subunit-related protein gene expression.
347	18753309	Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP/G6PC2) is a major autoantigen in both mouse and human type 1 diabetes.
348	18753309	Chromatin immunoprecipitation (ChIP) assays have shown that the IGRP promoter binds the islet-enriched transcription factors Pax-6 and BETA2.
349	18753309	We show here, again using ChIP assays, that the IGRP promoter also binds the islet-enriched transcription factors MafA and Foxa2.
350	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.
351	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.
352	18753309	Foxa2 and MafA regulate islet-specific glucose-6-phosphatase catalytic subunit-related protein gene expression.
353	18753309	Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP/G6PC2) is a major autoantigen in both mouse and human type 1 diabetes.
354	18753309	Chromatin immunoprecipitation (ChIP) assays have shown that the IGRP promoter binds the islet-enriched transcription factors Pax-6 and BETA2.
355	18753309	We show here, again using ChIP assays, that the IGRP promoter also binds the islet-enriched transcription factors MafA and Foxa2.
356	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.
357	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.
358	18753309	Foxa2 and MafA regulate islet-specific glucose-6-phosphatase catalytic subunit-related protein gene expression.
359	18753309	Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP/G6PC2) is a major autoantigen in both mouse and human type 1 diabetes.
360	18753309	Chromatin immunoprecipitation (ChIP) assays have shown that the IGRP promoter binds the islet-enriched transcription factors Pax-6 and BETA2.
361	18753309	We show here, again using ChIP assays, that the IGRP promoter also binds the islet-enriched transcription factors MafA and Foxa2.
362	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.
363	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.
364	19096518	Novel association of HK1 with glycated hemoglobin in a non-diabetic population: a genome-wide evaluation of 14,618 participants in the Women's Genome Health Study.
365	19096518	The results show that glycated hemoglobin levels are associated with genetic variation at the GCK (rs730497; P = 2.8 x 10(-12)), SLC30A8 (rs13266634; P = 9.8 x 10(-8)), G6PC2 (rs1402837; P = 6.8 x 10(-10)), and HK1 (rs7072268; P = 6.4 x 10(-9)) loci.
366	19096518	While associations at the GCK, SLC30A8, and G6PC2 loci are confirmatory, the findings at HK1 are novel.
367	19096518	This observed genetic association between glycated hemoglobin levels and HK1 polymorphisms paves the way for further studies of the role of HK1 in hemoglobin glycation, glucose metabolism, and diabetes.
368	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.
369	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.
370	19188044	Splenocytes from recipients of KOT splenocytes produced IL-10 (/IFN-gamma) upon GAD65 stimulation, whereas those from recipients of WTT splenocytes did not.
371	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.
372	19209463	IGRP is also a target of CD8 T cell responses in human T1D patients.
373	19209463	In NOD mice, most IGRP-reactive CD8 T cells target the IGRP(206-214) epitope and are diabetogenic.
374	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.
375	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.
376	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.
377	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.
378	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.
379	19209463	IGRP is also a target of CD8 T cell responses in human T1D patients.
380	19209463	In NOD mice, most IGRP-reactive CD8 T cells target the IGRP(206-214) epitope and are diabetogenic.
381	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.
382	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.
383	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.
384	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.
385	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.
386	19209463	IGRP is also a target of CD8 T cell responses in human T1D patients.
387	19209463	In NOD mice, most IGRP-reactive CD8 T cells target the IGRP(206-214) epitope and are diabetogenic.
388	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.
389	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.
390	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.
391	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.
392	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.
393	19209463	IGRP is also a target of CD8 T cell responses in human T1D patients.
394	19209463	In NOD mice, most IGRP-reactive CD8 T cells target the IGRP(206-214) epitope and are diabetogenic.
395	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.
396	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.
397	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.
398	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.
399	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.
400	19209463	IGRP is also a target of CD8 T cell responses in human T1D patients.
401	19209463	In NOD mice, most IGRP-reactive CD8 T cells target the IGRP(206-214) epitope and are diabetogenic.
402	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.
403	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.
404	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.
405	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.
406	19533084	Combined effects of single-nucleotide polymorphisms in GCK, GCKR, G6PC2 and MTNR1B on fasting plasma glucose and type 2 diabetes risk.
407	19669124	A variant in the G6PC2/ABCB11 locus is associated with increased fasting plasma glucose, increased basal hepatic glucose production and increased insulin release after oral and intravenous glucose loads.
408	19700406	Glucose-6-phosphatase catalytic subunit gene family.
409	19700406	The G6PC gene family contains three members, designated G6PC, G6PC2, and G6PC3.
410	19886740	Unexpectedly, the ratio of CD4(+):CD8(+) T cells was tightly controlled in the islets throughout diabetogenesis.
411	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.
412	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.
413	20082465	Investigations included sequencing of GCK, ABCC8, IPF1, NEUROD1, PTF1A, HNF1B, INS, ISL1, NGN3, HHEX, G6PC2, TCF7L2, SOX4, FOXP3 (Patients 1 and 2), GATA4 and KCNJ11 genes (all three patients), but no mutations were found.
414	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.
415	20220085	Toxin-coupled MHC class I tetramers can specifically ablate autoreactive CD8+ T cells and delay diabetes in nonobese diabetic mice.
416	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.
417	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.
418	20220085	Toxin-coupled MHC class I tetramers can specifically ablate autoreactive CD8+ T cells and delay diabetes in nonobese diabetic mice.
419	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.
420	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.
421	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.
422	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.
423	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.
424	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.
425	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.
426	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.
427	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.
428	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.
429	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.
430	20628598	Common polymorphisms in MTNR1B, G6PC2 and GCK are associated with increased fasting plasma glucose and impaired beta-cell function in Chinese subjects.
431	20668700	Effects of GCK, GCKR, G6PC2 and MTNR1B variants on glucose metabolism and insulin secretion.
432	20826583	The impact of genetic variation in the G6PC2 gene on insulin secretion depends on glycemia.
433	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.
434	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.
435	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.
436	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.
437	22069258	T cells target various antigens such as insulin, chromogranin A, glutamic acid decarboxylase and islet-specific glucose-6-phosphatase catalytic subunit-related protein.
438	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.
439	22438186	A SNP in G6PC2 predicts insulin secretion in type 1 diabetes.
440	22438186	Patients were genotyped for SNPs related to glucose metabolism: CDKAL1 rs7754840, G6PC2 rs560887, HHEX rs1111875, KCNJ11 rs5215.
441	22438186	In a longitudinal survival analysis, homozygosity for the minor allele (A) in G6PC2 predicted more rapid loss of insulin secretion over time.
442	22438186	A SNP in the beta cell gene G6PC2 may correlate with preserved insulin secretion in type 1 diabetes.
443	22438186	A SNP in G6PC2 predicts insulin secretion in type 1 diabetes.
444	22438186	Patients were genotyped for SNPs related to glucose metabolism: CDKAL1 rs7754840, G6PC2 rs560887, HHEX rs1111875, KCNJ11 rs5215.
445	22438186	In a longitudinal survival analysis, homozygosity for the minor allele (A) in G6PC2 predicted more rapid loss of insulin secretion over time.
446	22438186	A SNP in the beta cell gene G6PC2 may correlate with preserved insulin secretion in type 1 diabetes.
447	22438186	A SNP in G6PC2 predicts insulin secretion in type 1 diabetes.
448	22438186	Patients were genotyped for SNPs related to glucose metabolism: CDKAL1 rs7754840, G6PC2 rs560887, HHEX rs1111875, KCNJ11 rs5215.
449	22438186	In a longitudinal survival analysis, homozygosity for the minor allele (A) in G6PC2 predicted more rapid loss of insulin secretion over time.
450	22438186	A SNP in the beta cell gene G6PC2 may correlate with preserved insulin secretion in type 1 diabetes.
451	22438186	A SNP in G6PC2 predicts insulin secretion in type 1 diabetes.
452	22438186	Patients were genotyped for SNPs related to glucose metabolism: CDKAL1 rs7754840, G6PC2 rs560887, HHEX rs1111875, KCNJ11 rs5215.
453	22438186	In a longitudinal survival analysis, homozygosity for the minor allele (A) in G6PC2 predicted more rapid loss of insulin secretion over time.
454	22438186	A SNP in the beta cell gene G6PC2 may correlate with preserved insulin secretion in type 1 diabetes.
455	22486180	HbA1c-based diabetes diagnosis among patients with glucokinase mutation (GCK-MODY) is affected by a genetic variant of glucose-6-phosphatase (G6PC2).
456	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).
457	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.
458	22908330	Autoantigen recognition is required for recruitment of IGRP(206-214)-autoreactive CD8+ T cells but is dispensable for tolerance.
459	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.
460	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.
461	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.
462	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.
463	22908330	Autoantigen recognition is required for recruitment of IGRP(206-214)-autoreactive CD8+ T cells but is dispensable for tolerance.
464	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.
465	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.
466	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.
467	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.
468	22908330	Autoantigen recognition is required for recruitment of IGRP(206-214)-autoreactive CD8+ T cells but is dispensable for tolerance.
469	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.
470	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.
471	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.
472	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.
473	22908330	Autoantigen recognition is required for recruitment of IGRP(206-214)-autoreactive CD8+ T cells but is dispensable for tolerance.
474	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.
475	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.
476	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.
477	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.
478	22908330	Autoantigen recognition is required for recruitment of IGRP(206-214)-autoreactive CD8+ T cells but is dispensable for tolerance.
479	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.
480	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.
481	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.
482	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.
483	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.
484	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.
485	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.
486	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.
487	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.
488	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.
489	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.
490	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.
491	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.
492	22984506	We genotyped previously reported polymorphisms (or their proxies) in/near G6PC2, MTNR1B, GCK, DGKB, GCKR, ADCY5, MADD, CRY2, ADRA2A, FADS1, PROX1, SLC2A2, GLIS3, C2CD4B, IGF1, and IRS1 in 3,548 Diabetes Prevention Program participants.
493	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).
494	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.
495	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.
496	23155466	Using the HLA-A2 NOD-scid IL2rγ(null) mouse model, HLA-A2-restricted IGRP-specific CD8 T-cells induced a destructive insulitis.
497	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).
498	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.
499	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.
500	23155466	Using the HLA-A2 NOD-scid IL2rγ(null) mouse model, HLA-A2-restricted IGRP-specific CD8 T-cells induced a destructive insulitis.
501	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).
502	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.
503	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.
504	23155466	Using the HLA-A2 NOD-scid IL2rγ(null) mouse model, HLA-A2-restricted IGRP-specific CD8 T-cells induced a destructive insulitis.
505	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).
506	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.
507	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.
508	23155466	Using the HLA-A2 NOD-scid IL2rγ(null) mouse model, HLA-A2-restricted IGRP-specific CD8 T-cells induced a destructive insulitis.
509	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).
510	23840762	Large scale meta-analyses of fasting plasma glucose raising variants in GCK, GCKR, MTNR1B and G6PC2 and their impacts on type 2 diabetes mellitus risk.