Anx7 Is Required for Nutritional Control of Gene Expression in Mouse Pancreatic Islets of Langerhans

Background Gene expression in islets of Langerhans is profoundly sensitive to glucose and other nutrients. Islets of Langerhans in the Anx7(+/−) knockout mouse exhibit a profound reduction in ITPR3 protein expression, defective intracellular calcium signaling, and defective insulin secretion. Additional data presented here also show that mRNA for ITPR3 is virtually undetectable in isolated Anx7(+/−) islets. IP3Receptor type 3 (ITPR3) expression in islets of Langerhans is closely regulated by secretory stimuli, and it has been suggested that the level of the ITPR3 expression controls the ability of the islets to respond to nutritional signals. We report that although control islets respond to glucose in vitro by a transient increment in ITPR3 mRNA, the islets from the Anx7(+/−) mouse remain low. We therefore hypothesized that the Anx7/IP3 Receptor(3)/$ Ca^{2+} $ signaling pathway plays a role in β cell responses to glucose, and that in the absence of the Anx7/ITPR3 signaling system, the islets would be unable to discriminate between fed or fasted states in vivo. Materials and Methods To test this hypothesis, we subjected Anx7(+/−) and control mice to either food and water ad libidum or to an overnight fast with access to water only. We then isolated the respective islets and compared nutrient-dependent changes in global gene expression under the four conditions using genome-based microarray technology. Results Anx7 protein expression in these islets is only about 50% of control levels in normal littermate controls, and IPTR3 message and protein are virtually zero. cDNA microarray analyses show that in control animals gene expression is significantly affected by the fasting state. Many of the affected genes have historical relevance to development and differentiation of islets. These include preproglucagon, APOJ, cadherin2, phosphoglucoisomerase, oncostatin M, PAX6, HGF, and cytokeratin 18. However, there are also many other nutritionally sensitive genes in control islets that are principally associated with cell division and DNA repair. The latter genes have not specifically been associated with islet physiology in the past. By contrast, Anx7(+/−) mouse islets exhibit a greatly reduced ability to discriminate genomically between fed and fasted states for all classes of identified genes. Many of the validated genes are specific to islets in comparison to liver tissue examined. Real-time quantitative RT-PCR analysis of islets from Anx7 heterozygous mice and littermate controls revealed remarkable down-regulation in PTEN, Glut-2, PDX-1, IGF-1, and Neuro D1 expression, but not in liver. Conclusions We conclude that reduced gene dosage in the Anx7(+/−) islet, with concomitant loss of ITPR3 expression and consequent defects in $ Ca^{2+} $ signaling, may substantially contribute to the mechanism of the loss of genomic discrimination, in vivo, between the fed and fasted states. We believe that the requirement for complete Anx7 gene dosage and IPTR3 expression in islets of Langerhans will prove to be of fundamental importance for understanding the mechanism of nutritional sensing in health and disease. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Srivastava, Meera [verfasserIn] Eidelman, Ofer Leighton, Ximena Glasman, Mirta Goping, Gertrude Pollard, Harvey B.

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2002

Schlagwörter:	Inositol 1,4,5 Triphosphate Receptor, Type 3 (ITPR3) Control Islets ANXA5 Gene Mouse Islets Normal Littermate Controls

Anmerkung:	© NSLIJ Research Institute 2002

Übergeordnetes Werk:	Enthalten in: Molecular medicine - [London] : BioMed Central, 1994, 8(2002), 12 vom: 01. Dez., Seite 781-797
Übergeordnetes Werk:	volume:8 ; year:2002 ; number:12 ; day:01 ; month:12 ; pages:781-797

Links:	Volltext

DOI / URN:	10.1007/BF03402083

Katalog-ID:	SPR008059136

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520			\|a Background Gene expression in islets of Langerhans is profoundly sensitive to glucose and other nutrients. Islets of Langerhans in the Anx7(+/−) knockout mouse exhibit a profound reduction in ITPR3 protein expression, defective intracellular calcium signaling, and defective insulin secretion. Additional data presented here also show that mRNA for ITPR3 is virtually undetectable in isolated Anx7(+/−) islets. IP3Receptor type 3 (ITPR3) expression in islets of Langerhans is closely regulated by secretory stimuli, and it has been suggested that the level of the ITPR3 expression controls the ability of the islets to respond to nutritional signals. We report that although control islets respond to glucose in vitro by a transient increment in ITPR3 mRNA, the islets from the Anx7(+/−) mouse remain low. We therefore hypothesized that the Anx7/IP3 Receptor(3)/$ Ca^{2+} $ signaling pathway plays a role in β cell responses to glucose, and that in the absence of the Anx7/ITPR3 signaling system, the islets would be unable to discriminate between fed or fasted states in vivo. Materials and Methods To test this hypothesis, we subjected Anx7(+/−) and control mice to either food and water ad libidum or to an overnight fast with access to water only. We then isolated the respective islets and compared nutrient-dependent changes in global gene expression under the four conditions using genome-based microarray technology. Results Anx7 protein expression in these islets is only about 50% of control levels in normal littermate controls, and IPTR3 message and protein are virtually zero. cDNA microarray analyses show that in control animals gene expression is significantly affected by the fasting state. Many of the affected genes have historical relevance to development and differentiation of islets. These include preproglucagon, APOJ, cadherin2, phosphoglucoisomerase, oncostatin M, PAX6, HGF, and cytokeratin 18. However, there are also many other nutritionally sensitive genes in control islets that are principally associated with cell division and DNA repair. The latter genes have not specifically been associated with islet physiology in the past. By contrast, Anx7(+/−) mouse islets exhibit a greatly reduced ability to discriminate genomically between fed and fasted states for all classes of identified genes. Many of the validated genes are specific to islets in comparison to liver tissue examined. Real-time quantitative RT-PCR analysis of islets from Anx7 heterozygous mice and littermate controls revealed remarkable down-regulation in PTEN, Glut-2, PDX-1, IGF-1, and Neuro D1 expression, but not in liver. Conclusions We conclude that reduced gene dosage in the Anx7(+/−) islet, with concomitant loss of ITPR3 expression and consequent defects in $ Ca^{2+} $ signaling, may substantially contribute to the mechanism of the loss of genomic discrimination, in vivo, between the fed and fasted states. We believe that the requirement for complete Anx7 gene dosage and IPTR3 expression in islets of Langerhans will prove to be of fundamental importance for understanding the mechanism of nutritional sensing in health and disease.
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allfields	10.1007/BF03402083 doi (DE-627)SPR008059136 (SPR)BF03402083-e DE-627 ger DE-627 rakwb eng Srivastava, Meera verfasserin aut Anx7 Is Required for Nutritional Control of Gene Expression in Mouse Pancreatic Islets of Langerhans 2002 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © NSLIJ Research Institute 2002 Background Gene expression in islets of Langerhans is profoundly sensitive to glucose and other nutrients. Islets of Langerhans in the Anx7(+/−) knockout mouse exhibit a profound reduction in ITPR3 protein expression, defective intracellular calcium signaling, and defective insulin secretion. Additional data presented here also show that mRNA for ITPR3 is virtually undetectable in isolated Anx7(+/−) islets. IP3Receptor type 3 (ITPR3) expression in islets of Langerhans is closely regulated by secretory stimuli, and it has been suggested that the level of the ITPR3 expression controls the ability of the islets to respond to nutritional signals. We report that although control islets respond to glucose in vitro by a transient increment in ITPR3 mRNA, the islets from the Anx7(+/−) mouse remain low. We therefore hypothesized that the Anx7/IP3 Receptor(3)/$ Ca^{2+} $ signaling pathway plays a role in β cell responses to glucose, and that in the absence of the Anx7/ITPR3 signaling system, the islets would be unable to discriminate between fed or fasted states in vivo. Materials and Methods To test this hypothesis, we subjected Anx7(+/−) and control mice to either food and water ad libidum or to an overnight fast with access to water only. We then isolated the respective islets and compared nutrient-dependent changes in global gene expression under the four conditions using genome-based microarray technology. Results Anx7 protein expression in these islets is only about 50% of control levels in normal littermate controls, and IPTR3 message and protein are virtually zero. cDNA microarray analyses show that in control animals gene expression is significantly affected by the fasting state. Many of the affected genes have historical relevance to development and differentiation of islets. These include preproglucagon, APOJ, cadherin2, phosphoglucoisomerase, oncostatin M, PAX6, HGF, and cytokeratin 18. However, there are also many other nutritionally sensitive genes in control islets that are principally associated with cell division and DNA repair. The latter genes have not specifically been associated with islet physiology in the past. By contrast, Anx7(+/−) mouse islets exhibit a greatly reduced ability to discriminate genomically between fed and fasted states for all classes of identified genes. Many of the validated genes are specific to islets in comparison to liver tissue examined. Real-time quantitative RT-PCR analysis of islets from Anx7 heterozygous mice and littermate controls revealed remarkable down-regulation in PTEN, Glut-2, PDX-1, IGF-1, and Neuro D1 expression, but not in liver. Conclusions We conclude that reduced gene dosage in the Anx7(+/−) islet, with concomitant loss of ITPR3 expression and consequent defects in $ Ca^{2+} $ signaling, may substantially contribute to the mechanism of the loss of genomic discrimination, in vivo, between the fed and fasted states. We believe that the requirement for complete Anx7 gene dosage and IPTR3 expression in islets of Langerhans will prove to be of fundamental importance for understanding the mechanism of nutritional sensing in health and disease. Inositol 1,4,5 Triphosphate Receptor, Type 3 (ITPR3) (dpeaa)DE-He213 Control Islets (dpeaa)DE-He213 ANXA5 Gene (dpeaa)DE-He213 Mouse Islets (dpeaa)DE-He213 Normal Littermate Controls (dpeaa)DE-He213 Eidelman, Ofer aut Leighton, Ximena aut Glasman, Mirta aut Goping, Gertrude aut Pollard, Harvey B. aut Enthalten in Molecular medicine [London] : BioMed Central, 1994 8(2002), 12 vom: 01. Dez., Seite 781-797 (DE-627)269539611 (DE-600)1475577-4 1528-3658 nnns volume:8 year:2002 number:12 day:01 month:12 pages:781-797 https://dx.doi.org/10.1007/BF03402083 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2875 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2002 12 01 12 781-797
spelling	10.1007/BF03402083 doi (DE-627)SPR008059136 (SPR)BF03402083-e DE-627 ger DE-627 rakwb eng Srivastava, Meera verfasserin aut Anx7 Is Required for Nutritional Control of Gene Expression in Mouse Pancreatic Islets of Langerhans 2002 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © NSLIJ Research Institute 2002 Background Gene expression in islets of Langerhans is profoundly sensitive to glucose and other nutrients. Islets of Langerhans in the Anx7(+/−) knockout mouse exhibit a profound reduction in ITPR3 protein expression, defective intracellular calcium signaling, and defective insulin secretion. Additional data presented here also show that mRNA for ITPR3 is virtually undetectable in isolated Anx7(+/−) islets. IP3Receptor type 3 (ITPR3) expression in islets of Langerhans is closely regulated by secretory stimuli, and it has been suggested that the level of the ITPR3 expression controls the ability of the islets to respond to nutritional signals. We report that although control islets respond to glucose in vitro by a transient increment in ITPR3 mRNA, the islets from the Anx7(+/−) mouse remain low. We therefore hypothesized that the Anx7/IP3 Receptor(3)/$ Ca^{2+} $ signaling pathway plays a role in β cell responses to glucose, and that in the absence of the Anx7/ITPR3 signaling system, the islets would be unable to discriminate between fed or fasted states in vivo. Materials and Methods To test this hypothesis, we subjected Anx7(+/−) and control mice to either food and water ad libidum or to an overnight fast with access to water only. We then isolated the respective islets and compared nutrient-dependent changes in global gene expression under the four conditions using genome-based microarray technology. Results Anx7 protein expression in these islets is only about 50% of control levels in normal littermate controls, and IPTR3 message and protein are virtually zero. cDNA microarray analyses show that in control animals gene expression is significantly affected by the fasting state. Many of the affected genes have historical relevance to development and differentiation of islets. These include preproglucagon, APOJ, cadherin2, phosphoglucoisomerase, oncostatin M, PAX6, HGF, and cytokeratin 18. However, there are also many other nutritionally sensitive genes in control islets that are principally associated with cell division and DNA repair. The latter genes have not specifically been associated with islet physiology in the past. By contrast, Anx7(+/−) mouse islets exhibit a greatly reduced ability to discriminate genomically between fed and fasted states for all classes of identified genes. Many of the validated genes are specific to islets in comparison to liver tissue examined. Real-time quantitative RT-PCR analysis of islets from Anx7 heterozygous mice and littermate controls revealed remarkable down-regulation in PTEN, Glut-2, PDX-1, IGF-1, and Neuro D1 expression, but not in liver. Conclusions We conclude that reduced gene dosage in the Anx7(+/−) islet, with concomitant loss of ITPR3 expression and consequent defects in $ Ca^{2+} $ signaling, may substantially contribute to the mechanism of the loss of genomic discrimination, in vivo, between the fed and fasted states. We believe that the requirement for complete Anx7 gene dosage and IPTR3 expression in islets of Langerhans will prove to be of fundamental importance for understanding the mechanism of nutritional sensing in health and disease. Inositol 1,4,5 Triphosphate Receptor, Type 3 (ITPR3) (dpeaa)DE-He213 Control Islets (dpeaa)DE-He213 ANXA5 Gene (dpeaa)DE-He213 Mouse Islets (dpeaa)DE-He213 Normal Littermate Controls (dpeaa)DE-He213 Eidelman, Ofer aut Leighton, Ximena aut Glasman, Mirta aut Goping, Gertrude aut Pollard, Harvey B. aut Enthalten in Molecular medicine [London] : BioMed Central, 1994 8(2002), 12 vom: 01. Dez., Seite 781-797 (DE-627)269539611 (DE-600)1475577-4 1528-3658 nnns volume:8 year:2002 number:12 day:01 month:12 pages:781-797 https://dx.doi.org/10.1007/BF03402083 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2875 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2002 12 01 12 781-797
allfields_unstemmed	10.1007/BF03402083 doi (DE-627)SPR008059136 (SPR)BF03402083-e DE-627 ger DE-627 rakwb eng Srivastava, Meera verfasserin aut Anx7 Is Required for Nutritional Control of Gene Expression in Mouse Pancreatic Islets of Langerhans 2002 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © NSLIJ Research Institute 2002 Background Gene expression in islets of Langerhans is profoundly sensitive to glucose and other nutrients. Islets of Langerhans in the Anx7(+/−) knockout mouse exhibit a profound reduction in ITPR3 protein expression, defective intracellular calcium signaling, and defective insulin secretion. Additional data presented here also show that mRNA for ITPR3 is virtually undetectable in isolated Anx7(+/−) islets. IP3Receptor type 3 (ITPR3) expression in islets of Langerhans is closely regulated by secretory stimuli, and it has been suggested that the level of the ITPR3 expression controls the ability of the islets to respond to nutritional signals. We report that although control islets respond to glucose in vitro by a transient increment in ITPR3 mRNA, the islets from the Anx7(+/−) mouse remain low. We therefore hypothesized that the Anx7/IP3 Receptor(3)/$ Ca^{2+} $ signaling pathway plays a role in β cell responses to glucose, and that in the absence of the Anx7/ITPR3 signaling system, the islets would be unable to discriminate between fed or fasted states in vivo. Materials and Methods To test this hypothesis, we subjected Anx7(+/−) and control mice to either food and water ad libidum or to an overnight fast with access to water only. We then isolated the respective islets and compared nutrient-dependent changes in global gene expression under the four conditions using genome-based microarray technology. Results Anx7 protein expression in these islets is only about 50% of control levels in normal littermate controls, and IPTR3 message and protein are virtually zero. cDNA microarray analyses show that in control animals gene expression is significantly affected by the fasting state. Many of the affected genes have historical relevance to development and differentiation of islets. These include preproglucagon, APOJ, cadherin2, phosphoglucoisomerase, oncostatin M, PAX6, HGF, and cytokeratin 18. However, there are also many other nutritionally sensitive genes in control islets that are principally associated with cell division and DNA repair. The latter genes have not specifically been associated with islet physiology in the past. By contrast, Anx7(+/−) mouse islets exhibit a greatly reduced ability to discriminate genomically between fed and fasted states for all classes of identified genes. Many of the validated genes are specific to islets in comparison to liver tissue examined. Real-time quantitative RT-PCR analysis of islets from Anx7 heterozygous mice and littermate controls revealed remarkable down-regulation in PTEN, Glut-2, PDX-1, IGF-1, and Neuro D1 expression, but not in liver. Conclusions We conclude that reduced gene dosage in the Anx7(+/−) islet, with concomitant loss of ITPR3 expression and consequent defects in $ Ca^{2+} $ signaling, may substantially contribute to the mechanism of the loss of genomic discrimination, in vivo, between the fed and fasted states. We believe that the requirement for complete Anx7 gene dosage and IPTR3 expression in islets of Langerhans will prove to be of fundamental importance for understanding the mechanism of nutritional sensing in health and disease. Inositol 1,4,5 Triphosphate Receptor, Type 3 (ITPR3) (dpeaa)DE-He213 Control Islets (dpeaa)DE-He213 ANXA5 Gene (dpeaa)DE-He213 Mouse Islets (dpeaa)DE-He213 Normal Littermate Controls (dpeaa)DE-He213 Eidelman, Ofer aut Leighton, Ximena aut Glasman, Mirta aut Goping, Gertrude aut Pollard, Harvey B. aut Enthalten in Molecular medicine [London] : BioMed Central, 1994 8(2002), 12 vom: 01. Dez., Seite 781-797 (DE-627)269539611 (DE-600)1475577-4 1528-3658 nnns volume:8 year:2002 number:12 day:01 month:12 pages:781-797 https://dx.doi.org/10.1007/BF03402083 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2875 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2002 12 01 12 781-797
allfieldsGer	10.1007/BF03402083 doi (DE-627)SPR008059136 (SPR)BF03402083-e DE-627 ger DE-627 rakwb eng Srivastava, Meera verfasserin aut Anx7 Is Required for Nutritional Control of Gene Expression in Mouse Pancreatic Islets of Langerhans 2002 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © NSLIJ Research Institute 2002 Background Gene expression in islets of Langerhans is profoundly sensitive to glucose and other nutrients. Islets of Langerhans in the Anx7(+/−) knockout mouse exhibit a profound reduction in ITPR3 protein expression, defective intracellular calcium signaling, and defective insulin secretion. Additional data presented here also show that mRNA for ITPR3 is virtually undetectable in isolated Anx7(+/−) islets. IP3Receptor type 3 (ITPR3) expression in islets of Langerhans is closely regulated by secretory stimuli, and it has been suggested that the level of the ITPR3 expression controls the ability of the islets to respond to nutritional signals. We report that although control islets respond to glucose in vitro by a transient increment in ITPR3 mRNA, the islets from the Anx7(+/−) mouse remain low. We therefore hypothesized that the Anx7/IP3 Receptor(3)/$ Ca^{2+} $ signaling pathway plays a role in β cell responses to glucose, and that in the absence of the Anx7/ITPR3 signaling system, the islets would be unable to discriminate between fed or fasted states in vivo. Materials and Methods To test this hypothesis, we subjected Anx7(+/−) and control mice to either food and water ad libidum or to an overnight fast with access to water only. We then isolated the respective islets and compared nutrient-dependent changes in global gene expression under the four conditions using genome-based microarray technology. Results Anx7 protein expression in these islets is only about 50% of control levels in normal littermate controls, and IPTR3 message and protein are virtually zero. cDNA microarray analyses show that in control animals gene expression is significantly affected by the fasting state. Many of the affected genes have historical relevance to development and differentiation of islets. These include preproglucagon, APOJ, cadherin2, phosphoglucoisomerase, oncostatin M, PAX6, HGF, and cytokeratin 18. However, there are also many other nutritionally sensitive genes in control islets that are principally associated with cell division and DNA repair. The latter genes have not specifically been associated with islet physiology in the past. By contrast, Anx7(+/−) mouse islets exhibit a greatly reduced ability to discriminate genomically between fed and fasted states for all classes of identified genes. Many of the validated genes are specific to islets in comparison to liver tissue examined. Real-time quantitative RT-PCR analysis of islets from Anx7 heterozygous mice and littermate controls revealed remarkable down-regulation in PTEN, Glut-2, PDX-1, IGF-1, and Neuro D1 expression, but not in liver. Conclusions We conclude that reduced gene dosage in the Anx7(+/−) islet, with concomitant loss of ITPR3 expression and consequent defects in $ Ca^{2+} $ signaling, may substantially contribute to the mechanism of the loss of genomic discrimination, in vivo, between the fed and fasted states. We believe that the requirement for complete Anx7 gene dosage and IPTR3 expression in islets of Langerhans will prove to be of fundamental importance for understanding the mechanism of nutritional sensing in health and disease. Inositol 1,4,5 Triphosphate Receptor, Type 3 (ITPR3) (dpeaa)DE-He213 Control Islets (dpeaa)DE-He213 ANXA5 Gene (dpeaa)DE-He213 Mouse Islets (dpeaa)DE-He213 Normal Littermate Controls (dpeaa)DE-He213 Eidelman, Ofer aut Leighton, Ximena aut Glasman, Mirta aut Goping, Gertrude aut Pollard, Harvey B. aut Enthalten in Molecular medicine [London] : BioMed Central, 1994 8(2002), 12 vom: 01. Dez., Seite 781-797 (DE-627)269539611 (DE-600)1475577-4 1528-3658 nnns volume:8 year:2002 number:12 day:01 month:12 pages:781-797 https://dx.doi.org/10.1007/BF03402083 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2875 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2002 12 01 12 781-797
allfieldsSound	10.1007/BF03402083 doi (DE-627)SPR008059136 (SPR)BF03402083-e DE-627 ger DE-627 rakwb eng Srivastava, Meera verfasserin aut Anx7 Is Required for Nutritional Control of Gene Expression in Mouse Pancreatic Islets of Langerhans 2002 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © NSLIJ Research Institute 2002 Background Gene expression in islets of Langerhans is profoundly sensitive to glucose and other nutrients. Islets of Langerhans in the Anx7(+/−) knockout mouse exhibit a profound reduction in ITPR3 protein expression, defective intracellular calcium signaling, and defective insulin secretion. Additional data presented here also show that mRNA for ITPR3 is virtually undetectable in isolated Anx7(+/−) islets. IP3Receptor type 3 (ITPR3) expression in islets of Langerhans is closely regulated by secretory stimuli, and it has been suggested that the level of the ITPR3 expression controls the ability of the islets to respond to nutritional signals. We report that although control islets respond to glucose in vitro by a transient increment in ITPR3 mRNA, the islets from the Anx7(+/−) mouse remain low. We therefore hypothesized that the Anx7/IP3 Receptor(3)/$ Ca^{2+} $ signaling pathway plays a role in β cell responses to glucose, and that in the absence of the Anx7/ITPR3 signaling system, the islets would be unable to discriminate between fed or fasted states in vivo. Materials and Methods To test this hypothesis, we subjected Anx7(+/−) and control mice to either food and water ad libidum or to an overnight fast with access to water only. We then isolated the respective islets and compared nutrient-dependent changes in global gene expression under the four conditions using genome-based microarray technology. Results Anx7 protein expression in these islets is only about 50% of control levels in normal littermate controls, and IPTR3 message and protein are virtually zero. cDNA microarray analyses show that in control animals gene expression is significantly affected by the fasting state. Many of the affected genes have historical relevance to development and differentiation of islets. These include preproglucagon, APOJ, cadherin2, phosphoglucoisomerase, oncostatin M, PAX6, HGF, and cytokeratin 18. However, there are also many other nutritionally sensitive genes in control islets that are principally associated with cell division and DNA repair. The latter genes have not specifically been associated with islet physiology in the past. By contrast, Anx7(+/−) mouse islets exhibit a greatly reduced ability to discriminate genomically between fed and fasted states for all classes of identified genes. Many of the validated genes are specific to islets in comparison to liver tissue examined. Real-time quantitative RT-PCR analysis of islets from Anx7 heterozygous mice and littermate controls revealed remarkable down-regulation in PTEN, Glut-2, PDX-1, IGF-1, and Neuro D1 expression, but not in liver. Conclusions We conclude that reduced gene dosage in the Anx7(+/−) islet, with concomitant loss of ITPR3 expression and consequent defects in $ Ca^{2+} $ signaling, may substantially contribute to the mechanism of the loss of genomic discrimination, in vivo, between the fed and fasted states. We believe that the requirement for complete Anx7 gene dosage and IPTR3 expression in islets of Langerhans will prove to be of fundamental importance for understanding the mechanism of nutritional sensing in health and disease. Inositol 1,4,5 Triphosphate Receptor, Type 3 (ITPR3) (dpeaa)DE-He213 Control Islets (dpeaa)DE-He213 ANXA5 Gene (dpeaa)DE-He213 Mouse Islets (dpeaa)DE-He213 Normal Littermate Controls (dpeaa)DE-He213 Eidelman, Ofer aut Leighton, Ximena aut Glasman, Mirta aut Goping, Gertrude aut Pollard, Harvey B. aut Enthalten in Molecular medicine [London] : BioMed Central, 1994 8(2002), 12 vom: 01. Dez., Seite 781-797 (DE-627)269539611 (DE-600)1475577-4 1528-3658 nnns volume:8 year:2002 number:12 day:01 month:12 pages:781-797 https://dx.doi.org/10.1007/BF03402083 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_2875 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2002 12 01 12 781-797
language	English
source	Enthalten in Molecular medicine 8(2002), 12 vom: 01. Dez., Seite 781-797 volume:8 year:2002 number:12 day:01 month:12 pages:781-797
sourceStr	Enthalten in Molecular medicine 8(2002), 12 vom: 01. Dez., Seite 781-797 volume:8 year:2002 number:12 day:01 month:12 pages:781-797
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Inositol 1,4,5 Triphosphate Receptor, Type 3 (ITPR3) Control Islets ANXA5 Gene Mouse Islets Normal Littermate Controls
isfreeaccess_bool	false
container_title	Molecular medicine
authorswithroles_txt_mv	Srivastava, Meera @@aut@@ Eidelman, Ofer @@aut@@ Leighton, Ximena @@aut@@ Glasman, Mirta @@aut@@ Goping, Gertrude @@aut@@ Pollard, Harvey B. @@aut@@
publishDateDaySort_date	2002-12-01T00:00:00Z
hierarchy_top_id	269539611
id	SPR008059136
language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR008059136</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20240222091159.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201005s2002 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1007/BF03402083</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR008059136</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)BF03402083-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Srivastava, Meera</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Anx7 Is Required for Nutritional Control of Gene Expression in Mouse Pancreatic Islets of Langerhans</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2002</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© NSLIJ Research Institute 2002</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background Gene expression in islets of Langerhans is profoundly sensitive to glucose and other nutrients. Islets of Langerhans in the Anx7(+/−) knockout mouse exhibit a profound reduction in ITPR3 protein expression, defective intracellular calcium signaling, and defective insulin secretion. Additional data presented here also show that mRNA for ITPR3 is virtually undetectable in isolated Anx7(+/−) islets. IP3Receptor type 3 (ITPR3) expression in islets of Langerhans is closely regulated by secretory stimuli, and it has been suggested that the level of the ITPR3 expression controls the ability of the islets to respond to nutritional signals. We report that although control islets respond to glucose in vitro by a transient increment in ITPR3 mRNA, the islets from the Anx7(+/−) mouse remain low. We therefore hypothesized that the Anx7/IP3 Receptor(3)/$ Ca^{2+} $ signaling pathway plays a role in β cell responses to glucose, and that in the absence of the Anx7/ITPR3 signaling system, the islets would be unable to discriminate between fed or fasted states in vivo. Materials and Methods To test this hypothesis, we subjected Anx7(+/−) and control mice to either food and water ad libidum or to an overnight fast with access to water only. We then isolated the respective islets and compared nutrient-dependent changes in global gene expression under the four conditions using genome-based microarray technology. Results Anx7 protein expression in these islets is only about 50% of control levels in normal littermate controls, and IPTR3 message and protein are virtually zero. cDNA microarray analyses show that in control animals gene expression is significantly affected by the fasting state. Many of the affected genes have historical relevance to development and differentiation of islets. These include preproglucagon, APOJ, cadherin2, phosphoglucoisomerase, oncostatin M, PAX6, HGF, and cytokeratin 18. However, there are also many other nutritionally sensitive genes in control islets that are principally associated with cell division and DNA repair. The latter genes have not specifically been associated with islet physiology in the past. By contrast, Anx7(+/−) mouse islets exhibit a greatly reduced ability to discriminate genomically between fed and fasted states for all classes of identified genes. Many of the validated genes are specific to islets in comparison to liver tissue examined. Real-time quantitative RT-PCR analysis of islets from Anx7 heterozygous mice and littermate controls revealed remarkable down-regulation in PTEN, Glut-2, PDX-1, IGF-1, and Neuro D1 expression, but not in liver. Conclusions We conclude that reduced gene dosage in the Anx7(+/−) islet, with concomitant loss of ITPR3 expression and consequent defects in $ Ca^{2+} $ signaling, may substantially contribute to the mechanism of the loss of genomic discrimination, in vivo, between the fed and fasted states. 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author	Srivastava, Meera
spellingShingle	Srivastava, Meera misc Inositol 1,4,5 Triphosphate Receptor, Type 3 (ITPR3) misc Control Islets misc ANXA5 Gene misc Mouse Islets misc Normal Littermate Controls Anx7 Is Required for Nutritional Control of Gene Expression in Mouse Pancreatic Islets of Langerhans
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topic_title	Anx7 Is Required for Nutritional Control of Gene Expression in Mouse Pancreatic Islets of Langerhans Inositol 1,4,5 Triphosphate Receptor, Type 3 (ITPR3) (dpeaa)DE-He213 Control Islets (dpeaa)DE-He213 ANXA5 Gene (dpeaa)DE-He213 Mouse Islets (dpeaa)DE-He213 Normal Littermate Controls (dpeaa)DE-He213
topic	misc Inositol 1,4,5 Triphosphate Receptor, Type 3 (ITPR3) misc Control Islets misc ANXA5 Gene misc Mouse Islets misc Normal Littermate Controls
topic_unstemmed	misc Inositol 1,4,5 Triphosphate Receptor, Type 3 (ITPR3) misc Control Islets misc ANXA5 Gene misc Mouse Islets misc Normal Littermate Controls
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title	Anx7 Is Required for Nutritional Control of Gene Expression in Mouse Pancreatic Islets of Langerhans
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title_full	Anx7 Is Required for Nutritional Control of Gene Expression in Mouse Pancreatic Islets of Langerhans
author_sort	Srivastava, Meera
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author_browse	Srivastava, Meera Eidelman, Ofer Leighton, Ximena Glasman, Mirta Goping, Gertrude Pollard, Harvey B.
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title_sort	anx7 is required for nutritional control of gene expression in mouse pancreatic islets of langerhans
title_auth	Anx7 Is Required for Nutritional Control of Gene Expression in Mouse Pancreatic Islets of Langerhans
abstract	Background Gene expression in islets of Langerhans is profoundly sensitive to glucose and other nutrients. Islets of Langerhans in the Anx7(+/−) knockout mouse exhibit a profound reduction in ITPR3 protein expression, defective intracellular calcium signaling, and defective insulin secretion. Additional data presented here also show that mRNA for ITPR3 is virtually undetectable in isolated Anx7(+/−) islets. IP3Receptor type 3 (ITPR3) expression in islets of Langerhans is closely regulated by secretory stimuli, and it has been suggested that the level of the ITPR3 expression controls the ability of the islets to respond to nutritional signals. We report that although control islets respond to glucose in vitro by a transient increment in ITPR3 mRNA, the islets from the Anx7(+/−) mouse remain low. We therefore hypothesized that the Anx7/IP3 Receptor(3)/$ Ca^{2+} $ signaling pathway plays a role in β cell responses to glucose, and that in the absence of the Anx7/ITPR3 signaling system, the islets would be unable to discriminate between fed or fasted states in vivo. Materials and Methods To test this hypothesis, we subjected Anx7(+/−) and control mice to either food and water ad libidum or to an overnight fast with access to water only. We then isolated the respective islets and compared nutrient-dependent changes in global gene expression under the four conditions using genome-based microarray technology. Results Anx7 protein expression in these islets is only about 50% of control levels in normal littermate controls, and IPTR3 message and protein are virtually zero. cDNA microarray analyses show that in control animals gene expression is significantly affected by the fasting state. Many of the affected genes have historical relevance to development and differentiation of islets. These include preproglucagon, APOJ, cadherin2, phosphoglucoisomerase, oncostatin M, PAX6, HGF, and cytokeratin 18. However, there are also many other nutritionally sensitive genes in control islets that are principally associated with cell division and DNA repair. The latter genes have not specifically been associated with islet physiology in the past. By contrast, Anx7(+/−) mouse islets exhibit a greatly reduced ability to discriminate genomically between fed and fasted states for all classes of identified genes. Many of the validated genes are specific to islets in comparison to liver tissue examined. Real-time quantitative RT-PCR analysis of islets from Anx7 heterozygous mice and littermate controls revealed remarkable down-regulation in PTEN, Glut-2, PDX-1, IGF-1, and Neuro D1 expression, but not in liver. Conclusions We conclude that reduced gene dosage in the Anx7(+/−) islet, with concomitant loss of ITPR3 expression and consequent defects in $ Ca^{2+} $ signaling, may substantially contribute to the mechanism of the loss of genomic discrimination, in vivo, between the fed and fasted states. We believe that the requirement for complete Anx7 gene dosage and IPTR3 expression in islets of Langerhans will prove to be of fundamental importance for understanding the mechanism of nutritional sensing in health and disease. © NSLIJ Research Institute 2002
abstractGer	Background Gene expression in islets of Langerhans is profoundly sensitive to glucose and other nutrients. Islets of Langerhans in the Anx7(+/−) knockout mouse exhibit a profound reduction in ITPR3 protein expression, defective intracellular calcium signaling, and defective insulin secretion. Additional data presented here also show that mRNA for ITPR3 is virtually undetectable in isolated Anx7(+/−) islets. IP3Receptor type 3 (ITPR3) expression in islets of Langerhans is closely regulated by secretory stimuli, and it has been suggested that the level of the ITPR3 expression controls the ability of the islets to respond to nutritional signals. We report that although control islets respond to glucose in vitro by a transient increment in ITPR3 mRNA, the islets from the Anx7(+/−) mouse remain low. We therefore hypothesized that the Anx7/IP3 Receptor(3)/$ Ca^{2+} $ signaling pathway plays a role in β cell responses to glucose, and that in the absence of the Anx7/ITPR3 signaling system, the islets would be unable to discriminate between fed or fasted states in vivo. Materials and Methods To test this hypothesis, we subjected Anx7(+/−) and control mice to either food and water ad libidum or to an overnight fast with access to water only. We then isolated the respective islets and compared nutrient-dependent changes in global gene expression under the four conditions using genome-based microarray technology. Results Anx7 protein expression in these islets is only about 50% of control levels in normal littermate controls, and IPTR3 message and protein are virtually zero. cDNA microarray analyses show that in control animals gene expression is significantly affected by the fasting state. Many of the affected genes have historical relevance to development and differentiation of islets. These include preproglucagon, APOJ, cadherin2, phosphoglucoisomerase, oncostatin M, PAX6, HGF, and cytokeratin 18. However, there are also many other nutritionally sensitive genes in control islets that are principally associated with cell division and DNA repair. The latter genes have not specifically been associated with islet physiology in the past. By contrast, Anx7(+/−) mouse islets exhibit a greatly reduced ability to discriminate genomically between fed and fasted states for all classes of identified genes. Many of the validated genes are specific to islets in comparison to liver tissue examined. Real-time quantitative RT-PCR analysis of islets from Anx7 heterozygous mice and littermate controls revealed remarkable down-regulation in PTEN, Glut-2, PDX-1, IGF-1, and Neuro D1 expression, but not in liver. Conclusions We conclude that reduced gene dosage in the Anx7(+/−) islet, with concomitant loss of ITPR3 expression and consequent defects in $ Ca^{2+} $ signaling, may substantially contribute to the mechanism of the loss of genomic discrimination, in vivo, between the fed and fasted states. We believe that the requirement for complete Anx7 gene dosage and IPTR3 expression in islets of Langerhans will prove to be of fundamental importance for understanding the mechanism of nutritional sensing in health and disease. © NSLIJ Research Institute 2002
abstract_unstemmed	Background Gene expression in islets of Langerhans is profoundly sensitive to glucose and other nutrients. Islets of Langerhans in the Anx7(+/−) knockout mouse exhibit a profound reduction in ITPR3 protein expression, defective intracellular calcium signaling, and defective insulin secretion. Additional data presented here also show that mRNA for ITPR3 is virtually undetectable in isolated Anx7(+/−) islets. IP3Receptor type 3 (ITPR3) expression in islets of Langerhans is closely regulated by secretory stimuli, and it has been suggested that the level of the ITPR3 expression controls the ability of the islets to respond to nutritional signals. We report that although control islets respond to glucose in vitro by a transient increment in ITPR3 mRNA, the islets from the Anx7(+/−) mouse remain low. We therefore hypothesized that the Anx7/IP3 Receptor(3)/$ Ca^{2+} $ signaling pathway plays a role in β cell responses to glucose, and that in the absence of the Anx7/ITPR3 signaling system, the islets would be unable to discriminate between fed or fasted states in vivo. Materials and Methods To test this hypothesis, we subjected Anx7(+/−) and control mice to either food and water ad libidum or to an overnight fast with access to water only. We then isolated the respective islets and compared nutrient-dependent changes in global gene expression under the four conditions using genome-based microarray technology. Results Anx7 protein expression in these islets is only about 50% of control levels in normal littermate controls, and IPTR3 message and protein are virtually zero. cDNA microarray analyses show that in control animals gene expression is significantly affected by the fasting state. Many of the affected genes have historical relevance to development and differentiation of islets. These include preproglucagon, APOJ, cadherin2, phosphoglucoisomerase, oncostatin M, PAX6, HGF, and cytokeratin 18. However, there are also many other nutritionally sensitive genes in control islets that are principally associated with cell division and DNA repair. The latter genes have not specifically been associated with islet physiology in the past. By contrast, Anx7(+/−) mouse islets exhibit a greatly reduced ability to discriminate genomically between fed and fasted states for all classes of identified genes. Many of the validated genes are specific to islets in comparison to liver tissue examined. Real-time quantitative RT-PCR analysis of islets from Anx7 heterozygous mice and littermate controls revealed remarkable down-regulation in PTEN, Glut-2, PDX-1, IGF-1, and Neuro D1 expression, but not in liver. Conclusions We conclude that reduced gene dosage in the Anx7(+/−) islet, with concomitant loss of ITPR3 expression and consequent defects in $ Ca^{2+} $ signaling, may substantially contribute to the mechanism of the loss of genomic discrimination, in vivo, between the fed and fasted states. We believe that the requirement for complete Anx7 gene dosage and IPTR3 expression in islets of Langerhans will prove to be of fundamental importance for understanding the mechanism of nutritional sensing in health and disease. © NSLIJ Research Institute 2002
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title_short	Anx7 Is Required for Nutritional Control of Gene Expression in Mouse Pancreatic Islets of Langerhans
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The latter genes have not specifically been associated with islet physiology in the past. By contrast, Anx7(+/−) mouse islets exhibit a greatly reduced ability to discriminate genomically between fed and fasted states for all classes of identified genes. Many of the validated genes are specific to islets in comparison to liver tissue examined. Real-time quantitative RT-PCR analysis of islets from Anx7 heterozygous mice and littermate controls revealed remarkable down-regulation in PTEN, Glut-2, PDX-1, IGF-1, and Neuro D1 expression, but not in liver. Conclusions We conclude that reduced gene dosage in the Anx7(+/−) islet, with concomitant loss of ITPR3 expression and consequent defects in $ Ca^{2+} $ signaling, may substantially contribute to the mechanism of the loss of genomic discrimination, in vivo, between the fed and fasted states. 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Anx7 Is Required for Nutritional Control of Gene Expression in Mouse Pancreatic Islets of Langerhans

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