Molecular mechanisms of tungstate-induced pancreatic plasticity: A transcriptomics approach

Autores
Altirriba, Jordi; Barbera, Albert; del Zotto, Hector Herminio; Nadal, Belen; Piquer, Sandra; Sánchez Pla, Alex; Gagliardino, Juan Jose; Gomis, Ramon
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Sodium tungstate is known to be an effective anti-diabetic agent, able to increase beta cell mass in animal models of diabetes, although the molecular mechanisms of this treatment and the genes that control pancreas plasticity are yet to be identified. Using a transcriptomics approach, the aim of the study is to unravel the molecular mechanisms which participate in the recovery of exocrine and endocrine function of streptozotocin (STZ) diabetic rats treated with tungstate, determining the hyperglycemia contribution and the direct effect of tungstate. Results: Streptozotocin (STZ)-diabetic rats were treated orally with tungstate for five weeks. Treated (STZ)-diabetic rats showed a partial recovery of exocrine and endocrine function, with lower glycemia, increased insulinemia and amylasemia, and increased beta cell mass achieved by reducing beta cell apoptosis and raising beta cell proliferation. The microarray analysis of the pancreases led to the identification of three groups of differentially expressed genes: genes altered due to diabetes, genes restored by the treatment, and genes specifically induced by tungstate in the diabetic animals. The results were corroborated by quantitative PCR. A detailed description of the pathways involved in the pancreatic effects of tungstate is provided in this paper. Hyperglycemia contribution was studied in STZ-diabetic rats treated with phloridzin, and the direct effect of tungstate was determined in INS-1E cells treated with tungstate or serum from untreated or treated STZ-rats, observing that tungstate action in the pancreas takes places via hyperglycemia-independent pathways and via a combination of tungstate direct and indirect (through the serum profile modification) effects. Finally, the MAPK pathway was evaluated, observing that it has a key role in the tungstate-induced increase of beta cell proliferation as tungstate activates the mitogen-activated protein kinase (MAPK) pathway directly by increasing p42/p44 phosphorylation and indirectly by decreasing the expression of raf kinase inhibitor protein (Rkip), a negative modulator of the pathway. Conclusion: In conclusion, tungstate improves pancreatic function through a combination of hyperglycemia-independent pathways and through its own direct and indirect effects, whereas the MAPK pathway has a key role in the tungstate-induced increase of beta cell proliferation.
Fil: Altirriba, Jordi. Hospital Clinic de Barcelona; España. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas; España
Fil: Barbera, Albert. Hospital Clinic de Barcelona; España
Fil: del Zotto, Hector Herminio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Endocrinología Experimental y Aplicada (i); Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina
Fil: Nadal, Belen. Hospital Clinic de Barcelona; España. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas; España
Fil: Piquer, Sandra. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas; España. Hospital Clinic de Barcelona; España
Fil: Sánchez Pla, Alex. Universidad Autónoma de Barcelona. Hospital Vall D' Hebron; España. Universidad de Barcelona; España
Fil: Gagliardino, Juan Jose. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Endocrinología Experimental y Aplicada (i); Argentina
Fil: Gomis, Ramon. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas; España. Hospital Clinic de Barcelona; España
Materia
TUNGSTATO
CELULAS B
DIABETES
MASA DE CELULS B
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/96573
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/96573
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Molecular mechanisms of tungstate-induced pancreatic plasticity: A transcriptomics approachAltirriba, JordiBarbera, Albertdel Zotto, Hector HerminioNadal, BelenPiquer, SandraSánchez Pla, AlexGagliardino, Juan JoseGomis, RamonTUNGSTATOCELULAS BDIABETESMASA DE CELULS Bhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background: Sodium tungstate is known to be an effective anti-diabetic agent, able to increase beta cell mass in animal models of diabetes, although the molecular mechanisms of this treatment and the genes that control pancreas plasticity are yet to be identified. Using a transcriptomics approach, the aim of the study is to unravel the molecular mechanisms which participate in the recovery of exocrine and endocrine function of streptozotocin (STZ) diabetic rats treated with tungstate, determining the hyperglycemia contribution and the direct effect of tungstate. Results: Streptozotocin (STZ)-diabetic rats were treated orally with tungstate for five weeks. Treated (STZ)-diabetic rats showed a partial recovery of exocrine and endocrine function, with lower glycemia, increased insulinemia and amylasemia, and increased beta cell mass achieved by reducing beta cell apoptosis and raising beta cell proliferation. The microarray analysis of the pancreases led to the identification of three groups of differentially expressed genes: genes altered due to diabetes, genes restored by the treatment, and genes specifically induced by tungstate in the diabetic animals. The results were corroborated by quantitative PCR. A detailed description of the pathways involved in the pancreatic effects of tungstate is provided in this paper. Hyperglycemia contribution was studied in STZ-diabetic rats treated with phloridzin, and the direct effect of tungstate was determined in INS-1E cells treated with tungstate or serum from untreated or treated STZ-rats, observing that tungstate action in the pancreas takes places via hyperglycemia-independent pathways and via a combination of tungstate direct and indirect (through the serum profile modification) effects. Finally, the MAPK pathway was evaluated, observing that it has a key role in the tungstate-induced increase of beta cell proliferation as tungstate activates the mitogen-activated protein kinase (MAPK) pathway directly by increasing p42/p44 phosphorylation and indirectly by decreasing the expression of raf kinase inhibitor protein (Rkip), a negative modulator of the pathway. Conclusion: In conclusion, tungstate improves pancreatic function through a combination of hyperglycemia-independent pathways and through its own direct and indirect effects, whereas the MAPK pathway has a key role in the tungstate-induced increase of beta cell proliferation.Fil: Altirriba, Jordi. Hospital Clinic de Barcelona; España. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas; EspañaFil: Barbera, Albert. Hospital Clinic de Barcelona; EspañaFil: del Zotto, Hector Herminio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Endocrinología Experimental y Aplicada (i); Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; ArgentinaFil: Nadal, Belen. Hospital Clinic de Barcelona; España. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas; EspañaFil: Piquer, Sandra. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas; España. Hospital Clinic de Barcelona; EspañaFil: Sánchez Pla, Alex. Universidad Autónoma de Barcelona. Hospital Vall D' Hebron; España. Universidad de Barcelona; EspañaFil: Gagliardino, Juan Jose. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Endocrinología Experimental y Aplicada (i); ArgentinaFil: Gomis, Ramon. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas; España. Hospital Clinic de Barcelona; EspañaBioMed Central2009-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/96573Altirriba, Jordi; Barbera, Albert; del Zotto, Hector Herminio; Nadal, Belen; Piquer, Sandra; et al.; Molecular mechanisms of tungstate-induced pancreatic plasticity: A transcriptomics approach; BioMed Central; BMC Genomics; 10; 1; 8-2009; 1-131471-2164CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://bmcgenomics.biomedcentral.com/articles/10.1186/1471-2164-10-406info:eu-repo/semantics/altIdentifier/doi/10.1186/1471-2164-10-406info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:39:59Zoai:ri.conicet.gov.ar:11336/96573instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:39:59.561CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Molecular mechanisms of tungstate-induced pancreatic plasticity: A transcriptomics approach
title Molecular mechanisms of tungstate-induced pancreatic plasticity: A transcriptomics approach
spellingShingle Molecular mechanisms of tungstate-induced pancreatic plasticity: A transcriptomics approach
Altirriba, Jordi
TUNGSTATO
CELULAS B
DIABETES
MASA DE CELULS B
title_short Molecular mechanisms of tungstate-induced pancreatic plasticity: A transcriptomics approach
title_full Molecular mechanisms of tungstate-induced pancreatic plasticity: A transcriptomics approach
title_fullStr Molecular mechanisms of tungstate-induced pancreatic plasticity: A transcriptomics approach
title_full_unstemmed Molecular mechanisms of tungstate-induced pancreatic plasticity: A transcriptomics approach
title_sort Molecular mechanisms of tungstate-induced pancreatic plasticity: A transcriptomics approach
dc.creator.none.fl_str_mv Altirriba, Jordi
Barbera, Albert
del Zotto, Hector Herminio
Nadal, Belen
Piquer, Sandra
Sánchez Pla, Alex
Gagliardino, Juan Jose
Gomis, Ramon
author Altirriba, Jordi
author_facet Altirriba, Jordi
Barbera, Albert
del Zotto, Hector Herminio
Nadal, Belen
Piquer, Sandra
Sánchez Pla, Alex
Gagliardino, Juan Jose
Gomis, Ramon
author_role author
author2 Barbera, Albert
del Zotto, Hector Herminio
Nadal, Belen
Piquer, Sandra
Sánchez Pla, Alex
Gagliardino, Juan Jose
Gomis, Ramon
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv TUNGSTATO
CELULAS B
DIABETES
MASA DE CELULS B
topic TUNGSTATO
CELULAS B
DIABETES
MASA DE CELULS B
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: Sodium tungstate is known to be an effective anti-diabetic agent, able to increase beta cell mass in animal models of diabetes, although the molecular mechanisms of this treatment and the genes that control pancreas plasticity are yet to be identified. Using a transcriptomics approach, the aim of the study is to unravel the molecular mechanisms which participate in the recovery of exocrine and endocrine function of streptozotocin (STZ) diabetic rats treated with tungstate, determining the hyperglycemia contribution and the direct effect of tungstate. Results: Streptozotocin (STZ)-diabetic rats were treated orally with tungstate for five weeks. Treated (STZ)-diabetic rats showed a partial recovery of exocrine and endocrine function, with lower glycemia, increased insulinemia and amylasemia, and increased beta cell mass achieved by reducing beta cell apoptosis and raising beta cell proliferation. The microarray analysis of the pancreases led to the identification of three groups of differentially expressed genes: genes altered due to diabetes, genes restored by the treatment, and genes specifically induced by tungstate in the diabetic animals. The results were corroborated by quantitative PCR. A detailed description of the pathways involved in the pancreatic effects of tungstate is provided in this paper. Hyperglycemia contribution was studied in STZ-diabetic rats treated with phloridzin, and the direct effect of tungstate was determined in INS-1E cells treated with tungstate or serum from untreated or treated STZ-rats, observing that tungstate action in the pancreas takes places via hyperglycemia-independent pathways and via a combination of tungstate direct and indirect (through the serum profile modification) effects. Finally, the MAPK pathway was evaluated, observing that it has a key role in the tungstate-induced increase of beta cell proliferation as tungstate activates the mitogen-activated protein kinase (MAPK) pathway directly by increasing p42/p44 phosphorylation and indirectly by decreasing the expression of raf kinase inhibitor protein (Rkip), a negative modulator of the pathway. Conclusion: In conclusion, tungstate improves pancreatic function through a combination of hyperglycemia-independent pathways and through its own direct and indirect effects, whereas the MAPK pathway has a key role in the tungstate-induced increase of beta cell proliferation.
Fil: Altirriba, Jordi. Hospital Clinic de Barcelona; España. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas; España
Fil: Barbera, Albert. Hospital Clinic de Barcelona; España
Fil: del Zotto, Hector Herminio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Endocrinología Experimental y Aplicada (i); Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina
Fil: Nadal, Belen. Hospital Clinic de Barcelona; España. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas; España
Fil: Piquer, Sandra. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas; España. Hospital Clinic de Barcelona; España
Fil: Sánchez Pla, Alex. Universidad Autónoma de Barcelona. Hospital Vall D' Hebron; España. Universidad de Barcelona; España
Fil: Gagliardino, Juan Jose. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Endocrinología Experimental y Aplicada (i); Argentina
Fil: Gomis, Ramon. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas; España. Hospital Clinic de Barcelona; España
description Background: Sodium tungstate is known to be an effective anti-diabetic agent, able to increase beta cell mass in animal models of diabetes, although the molecular mechanisms of this treatment and the genes that control pancreas plasticity are yet to be identified. Using a transcriptomics approach, the aim of the study is to unravel the molecular mechanisms which participate in the recovery of exocrine and endocrine function of streptozotocin (STZ) diabetic rats treated with tungstate, determining the hyperglycemia contribution and the direct effect of tungstate. Results: Streptozotocin (STZ)-diabetic rats were treated orally with tungstate for five weeks. Treated (STZ)-diabetic rats showed a partial recovery of exocrine and endocrine function, with lower glycemia, increased insulinemia and amylasemia, and increased beta cell mass achieved by reducing beta cell apoptosis and raising beta cell proliferation. The microarray analysis of the pancreases led to the identification of three groups of differentially expressed genes: genes altered due to diabetes, genes restored by the treatment, and genes specifically induced by tungstate in the diabetic animals. The results were corroborated by quantitative PCR. A detailed description of the pathways involved in the pancreatic effects of tungstate is provided in this paper. Hyperglycemia contribution was studied in STZ-diabetic rats treated with phloridzin, and the direct effect of tungstate was determined in INS-1E cells treated with tungstate or serum from untreated or treated STZ-rats, observing that tungstate action in the pancreas takes places via hyperglycemia-independent pathways and via a combination of tungstate direct and indirect (through the serum profile modification) effects. Finally, the MAPK pathway was evaluated, observing that it has a key role in the tungstate-induced increase of beta cell proliferation as tungstate activates the mitogen-activated protein kinase (MAPK) pathway directly by increasing p42/p44 phosphorylation and indirectly by decreasing the expression of raf kinase inhibitor protein (Rkip), a negative modulator of the pathway. Conclusion: In conclusion, tungstate improves pancreatic function through a combination of hyperglycemia-independent pathways and through its own direct and indirect effects, whereas the MAPK pathway has a key role in the tungstate-induced increase of beta cell proliferation.
publishDate 2009
dc.date.none.fl_str_mv 2009-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/96573
Altirriba, Jordi; Barbera, Albert; del Zotto, Hector Herminio; Nadal, Belen; Piquer, Sandra; et al.; Molecular mechanisms of tungstate-induced pancreatic plasticity: A transcriptomics approach; BioMed Central; BMC Genomics; 10; 1; 8-2009; 1-13
1471-2164
CONICET Digital
CONICET
url http://hdl.handle.net/11336/96573
identifier_str_mv Altirriba, Jordi; Barbera, Albert; del Zotto, Hector Herminio; Nadal, Belen; Piquer, Sandra; et al.; Molecular mechanisms of tungstate-induced pancreatic plasticity: A transcriptomics approach; BioMed Central; BMC Genomics; 10; 1; 8-2009; 1-13
1471-2164
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://bmcgenomics.biomedcentral.com/articles/10.1186/1471-2164-10-406
info:eu-repo/semantics/altIdentifier/doi/10.1186/1471-2164-10-406
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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