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

Autores
Altirriba, Jordi; Barberá, Joan Albert; Del Zotto, Héctor Herminio; Nadal, Belén; Piquer, Sandra; Sánchez Pla, Alex; Gagliardino, Juan José; Gomis, Ramón
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.
Centro de Endocrinología Experimental y Aplicada
Materia
Ciencias Médicas
phlorizin
tungsten derivative
streptozocin
enzyme activation
pancreas
protein
diabetes
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by/3.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/35685

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network_name_str SEDICI (UNLP)
spelling Molecular mechanisms of tungstate-induced pancreatic plasticity: A transcriptomics approachAltirriba, JordiBarberá, Joan AlbertDel Zotto, Héctor HerminioNadal, BelénPiquer, SandraSánchez Pla, AlexGagliardino, Juan JoséGomis, RamónCiencias Médicasphlorizintungsten derivativestreptozocinenzyme activationpancreasproteindiabetesBackground: 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.Centro de Endocrinología Experimental y Aplicada2009-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://sedici.unlp.edu.ar/handle/10915/35685enginfo:eu-repo/semantics/altIdentifier/url/http://www.biomedcentral.com/content/pdf/1471-2164-10-406.pdfinfo:eu-repo/semantics/altIdentifier/issn/1471-2164info:eu-repo/semantics/altIdentifier/doi/10.1186/1471-2164-10-406info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/3.0/Creative Commons Attribution 3.0 Unported (CC BY 3.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-29T10:57:03Zoai:sedici.unlp.edu.ar:10915/35685Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-29 10:57:04.1SEDICI (UNLP) - Universidad Nacional de La Platafalse
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
Ciencias Médicas
phlorizin
tungsten derivative
streptozocin
enzyme activation
pancreas
protein
diabetes
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
Barberá, Joan Albert
Del Zotto, Héctor Herminio
Nadal, Belén
Piquer, Sandra
Sánchez Pla, Alex
Gagliardino, Juan José
Gomis, Ramón
author Altirriba, Jordi
author_facet Altirriba, Jordi
Barberá, Joan Albert
Del Zotto, Héctor Herminio
Nadal, Belén
Piquer, Sandra
Sánchez Pla, Alex
Gagliardino, Juan José
Gomis, Ramón
author_role author
author2 Barberá, Joan Albert
Del Zotto, Héctor Herminio
Nadal, Belén
Piquer, Sandra
Sánchez Pla, Alex
Gagliardino, Juan José
Gomis, Ramón
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ciencias Médicas
phlorizin
tungsten derivative
streptozocin
enzyme activation
pancreas
protein
diabetes
topic Ciencias Médicas
phlorizin
tungsten derivative
streptozocin
enzyme activation
pancreas
protein
diabetes
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.
Centro de Endocrinología Experimental y Aplicada
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
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status_str publishedVersion
dc.identifier.none.fl_str_mv http://sedici.unlp.edu.ar/handle/10915/35685
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dc.language.none.fl_str_mv eng
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info:eu-repo/semantics/altIdentifier/issn/1471-2164
info:eu-repo/semantics/altIdentifier/doi/10.1186/1471-2164-10-406
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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Creative Commons Attribution 3.0 Unported (CC BY 3.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/3.0/
Creative Commons Attribution 3.0 Unported (CC BY 3.0)
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instname:Universidad Nacional de La Plata
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