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
- Institución
- Universidad Nacional de La Plata
- OAI Identificador
- oai:sedici.unlp.edu.ar:10915/35685
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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 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Articulo http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
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http://sedici.unlp.edu.ar/handle/10915/35685 |
url |
http://sedici.unlp.edu.ar/handle/10915/35685 |
dc.language.none.fl_str_mv |
eng |
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eng |
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info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/3.0/ Creative Commons Attribution 3.0 Unported (CC BY 3.0) |
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openAccess |
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http://creativecommons.org/licenses/by/3.0/ Creative Commons Attribution 3.0 Unported (CC BY 3.0) |
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