Effects of islet neogenesis associated protein depend on vascular endothelial growth factor gene expression modulated by hypoxia-inducible factor 1-alpha

Autores
Román, Carolina Lisi; Maiztegui, Barbara; Mencucci, Maria Victoria; Ahrtz, Lucia; Algañarás, Macarena; del Zotto, Hector Herminio; Gagliardino, Juan Jose; Flores, Luis Emilio
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background Pharmacology has provided efficient tools to improve insulin effect/secretion but the decrease in β-cell mass remains elusive. INGAP-PP could provide a therapeutic alternative to meet that challenge. Aim To further understand the mechanism that links INGAP-PP effects upon β-cell mass and function with islet angiogenesis. Methodology Normal male Wistar rats were divided into 2 groups and injected with a single dose of 100 mg/Kg suramin or saline. Both groups were divided into 2 subgroups that received daily doses of 2 mg/kg INGAP-PP or saline for ten days. Plasma glucose, triacylglycerol, TBARS, and insulin levels were measured. Pancreas immunomorphometric analyses were also performed. Pancreatic islets were isolated to measure glucose-stimulated insulin secretion (GSIS). Specific islet mRNA levels were studied by qRT-PCR. Statistical analysis was done using ANOVA. Results No differences were recorded in body weight, food intake, or any other plasma parameter measured in all groups. Islets from INGAP-PP-treated rats significantly increased GSIS, β-cell mass, and mRNA levels of Bcl-2, Ngn-3, VEGF-A, VEGF-R2, CD31, Ang1 and Ang2, Laminin β-1, and Integrin β-1, and decreased mRNA levels of Caspase-8, Bad, and Bax. Islets from suramin-treated rats showed significant opposite effects, but INGAPP-PP administration rescued most of the suramin effects in animals treated with both compounds. Conclusion Our results reinforce the concept that INGAP-PP enhances insulin secretion and β-cell mass, acting through PI3K/Akt/mTOR pathways and simultaneously activating angiogenesis through HIF-1α-mediated VEGF-A secretion. Therefore, INGAP-PP might be a suitable antidiabetic agent able to overcome two major alterations present in T2D.
Fil: Román, Carolina Lisi. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina
Fil: Maiztegui, Barbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina
Fil: Mencucci, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina
Fil: Ahrtz, Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina
Fil: Algañarás, Macarena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina
Fil: del Zotto, Hector Herminio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina
Fil: Gagliardino, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina
Fil: Flores, Luis Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina
Materia
ANGIOGENESIS
HIF-1Α
INGAP-PP
MTOR PATHWAY
Β-CELLS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/122463
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/122463
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Effects of islet neogenesis associated protein depend on vascular endothelial growth factor gene expression modulated by hypoxia-inducible factor 1-alphaRomán, Carolina LisiMaiztegui, BarbaraMencucci, Maria VictoriaAhrtz, LuciaAlgañarás, Macarenadel Zotto, Hector HerminioGagliardino, Juan JoseFlores, Luis EmilioANGIOGENESISHIF-1ΑINGAP-PPMTOR PATHWAYΒ-CELLShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background Pharmacology has provided efficient tools to improve insulin effect/secretion but the decrease in β-cell mass remains elusive. INGAP-PP could provide a therapeutic alternative to meet that challenge. Aim To further understand the mechanism that links INGAP-PP effects upon β-cell mass and function with islet angiogenesis. Methodology Normal male Wistar rats were divided into 2 groups and injected with a single dose of 100 mg/Kg suramin or saline. Both groups were divided into 2 subgroups that received daily doses of 2 mg/kg INGAP-PP or saline for ten days. Plasma glucose, triacylglycerol, TBARS, and insulin levels were measured. Pancreas immunomorphometric analyses were also performed. Pancreatic islets were isolated to measure glucose-stimulated insulin secretion (GSIS). Specific islet mRNA levels were studied by qRT-PCR. Statistical analysis was done using ANOVA. Results No differences were recorded in body weight, food intake, or any other plasma parameter measured in all groups. Islets from INGAP-PP-treated rats significantly increased GSIS, β-cell mass, and mRNA levels of Bcl-2, Ngn-3, VEGF-A, VEGF-R2, CD31, Ang1 and Ang2, Laminin β-1, and Integrin β-1, and decreased mRNA levels of Caspase-8, Bad, and Bax. Islets from suramin-treated rats showed significant opposite effects, but INGAPP-PP administration rescued most of the suramin effects in animals treated with both compounds. Conclusion Our results reinforce the concept that INGAP-PP enhances insulin secretion and β-cell mass, acting through PI3K/Akt/mTOR pathways and simultaneously activating angiogenesis through HIF-1α-mediated VEGF-A secretion. Therefore, INGAP-PP might be a suitable antidiabetic agent able to overcome two major alterations present in T2D.Fil: Román, Carolina Lisi. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Maiztegui, Barbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Mencucci, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Ahrtz, Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Algañarás, Macarena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: del Zotto, Hector Herminio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Gagliardino, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Flores, Luis Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaElsevier Science Inc2019-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/122463Román, Carolina Lisi; Maiztegui, Barbara; Mencucci, Maria Victoria; Ahrtz, Lucia; Algañarás, Macarena; et al.; Effects of islet neogenesis associated protein depend on vascular endothelial growth factor gene expression modulated by hypoxia-inducible factor 1-alpha; Elsevier Science Inc; Peptides; 117; 170090; 7-20190196-9781CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/31121197info:eu-repo/semantics/altIdentifier/doi/10.1016/j.peptides.2019.05.002info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0196978119300622info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:21:39Zoai:ri.conicet.gov.ar:11336/122463instacron: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:34982025-09-10 13:21:39.991CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Effects of islet neogenesis associated protein depend on vascular endothelial growth factor gene expression modulated by hypoxia-inducible factor 1-alpha
title Effects of islet neogenesis associated protein depend on vascular endothelial growth factor gene expression modulated by hypoxia-inducible factor 1-alpha
spellingShingle Effects of islet neogenesis associated protein depend on vascular endothelial growth factor gene expression modulated by hypoxia-inducible factor 1-alpha
Román, Carolina Lisi
ANGIOGENESIS
HIF-1Α
INGAP-PP
MTOR PATHWAY
Β-CELLS
title_short Effects of islet neogenesis associated protein depend on vascular endothelial growth factor gene expression modulated by hypoxia-inducible factor 1-alpha
title_full Effects of islet neogenesis associated protein depend on vascular endothelial growth factor gene expression modulated by hypoxia-inducible factor 1-alpha
title_fullStr Effects of islet neogenesis associated protein depend on vascular endothelial growth factor gene expression modulated by hypoxia-inducible factor 1-alpha
title_full_unstemmed Effects of islet neogenesis associated protein depend on vascular endothelial growth factor gene expression modulated by hypoxia-inducible factor 1-alpha
title_sort Effects of islet neogenesis associated protein depend on vascular endothelial growth factor gene expression modulated by hypoxia-inducible factor 1-alpha
dc.creator.none.fl_str_mv Román, Carolina Lisi
Maiztegui, Barbara
Mencucci, Maria Victoria
Ahrtz, Lucia
Algañarás, Macarena
del Zotto, Hector Herminio
Gagliardino, Juan Jose
Flores, Luis Emilio
author Román, Carolina Lisi
author_facet Román, Carolina Lisi
Maiztegui, Barbara
Mencucci, Maria Victoria
Ahrtz, Lucia
Algañarás, Macarena
del Zotto, Hector Herminio
Gagliardino, Juan Jose
Flores, Luis Emilio
author_role author
author2 Maiztegui, Barbara
Mencucci, Maria Victoria
Ahrtz, Lucia
Algañarás, Macarena
del Zotto, Hector Herminio
Gagliardino, Juan Jose
Flores, Luis Emilio
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ANGIOGENESIS
HIF-1Α
INGAP-PP
MTOR PATHWAY
Β-CELLS
topic ANGIOGENESIS
HIF-1Α
INGAP-PP
MTOR PATHWAY
Β-CELLS
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 Pharmacology has provided efficient tools to improve insulin effect/secretion but the decrease in β-cell mass remains elusive. INGAP-PP could provide a therapeutic alternative to meet that challenge. Aim To further understand the mechanism that links INGAP-PP effects upon β-cell mass and function with islet angiogenesis. Methodology Normal male Wistar rats were divided into 2 groups and injected with a single dose of 100 mg/Kg suramin or saline. Both groups were divided into 2 subgroups that received daily doses of 2 mg/kg INGAP-PP or saline for ten days. Plasma glucose, triacylglycerol, TBARS, and insulin levels were measured. Pancreas immunomorphometric analyses were also performed. Pancreatic islets were isolated to measure glucose-stimulated insulin secretion (GSIS). Specific islet mRNA levels were studied by qRT-PCR. Statistical analysis was done using ANOVA. Results No differences were recorded in body weight, food intake, or any other plasma parameter measured in all groups. Islets from INGAP-PP-treated rats significantly increased GSIS, β-cell mass, and mRNA levels of Bcl-2, Ngn-3, VEGF-A, VEGF-R2, CD31, Ang1 and Ang2, Laminin β-1, and Integrin β-1, and decreased mRNA levels of Caspase-8, Bad, and Bax. Islets from suramin-treated rats showed significant opposite effects, but INGAPP-PP administration rescued most of the suramin effects in animals treated with both compounds. Conclusion Our results reinforce the concept that INGAP-PP enhances insulin secretion and β-cell mass, acting through PI3K/Akt/mTOR pathways and simultaneously activating angiogenesis through HIF-1α-mediated VEGF-A secretion. Therefore, INGAP-PP might be a suitable antidiabetic agent able to overcome two major alterations present in T2D.
Fil: Román, Carolina Lisi. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina
Fil: Maiztegui, Barbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina
Fil: Mencucci, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina
Fil: Ahrtz, Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina
Fil: Algañarás, Macarena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina
Fil: del Zotto, Hector Herminio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina
Fil: Gagliardino, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina
Fil: Flores, Luis Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina
description Background Pharmacology has provided efficient tools to improve insulin effect/secretion but the decrease in β-cell mass remains elusive. INGAP-PP could provide a therapeutic alternative to meet that challenge. Aim To further understand the mechanism that links INGAP-PP effects upon β-cell mass and function with islet angiogenesis. Methodology Normal male Wistar rats were divided into 2 groups and injected with a single dose of 100 mg/Kg suramin or saline. Both groups were divided into 2 subgroups that received daily doses of 2 mg/kg INGAP-PP or saline for ten days. Plasma glucose, triacylglycerol, TBARS, and insulin levels were measured. Pancreas immunomorphometric analyses were also performed. Pancreatic islets were isolated to measure glucose-stimulated insulin secretion (GSIS). Specific islet mRNA levels were studied by qRT-PCR. Statistical analysis was done using ANOVA. Results No differences were recorded in body weight, food intake, or any other plasma parameter measured in all groups. Islets from INGAP-PP-treated rats significantly increased GSIS, β-cell mass, and mRNA levels of Bcl-2, Ngn-3, VEGF-A, VEGF-R2, CD31, Ang1 and Ang2, Laminin β-1, and Integrin β-1, and decreased mRNA levels of Caspase-8, Bad, and Bax. Islets from suramin-treated rats showed significant opposite effects, but INGAPP-PP administration rescued most of the suramin effects in animals treated with both compounds. Conclusion Our results reinforce the concept that INGAP-PP enhances insulin secretion and β-cell mass, acting through PI3K/Akt/mTOR pathways and simultaneously activating angiogenesis through HIF-1α-mediated VEGF-A secretion. Therefore, INGAP-PP might be a suitable antidiabetic agent able to overcome two major alterations present in T2D.
publishDate 2019
dc.date.none.fl_str_mv 2019-07
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/11336/122463
Román, Carolina Lisi; Maiztegui, Barbara; Mencucci, Maria Victoria; Ahrtz, Lucia; Algañarás, Macarena; et al.; Effects of islet neogenesis associated protein depend on vascular endothelial growth factor gene expression modulated by hypoxia-inducible factor 1-alpha; Elsevier Science Inc; Peptides; 117; 170090; 7-2019
0196-9781
CONICET Digital
CONICET
url http://hdl.handle.net/11336/122463
identifier_str_mv Román, Carolina Lisi; Maiztegui, Barbara; Mencucci, Maria Victoria; Ahrtz, Lucia; Algañarás, Macarena; et al.; Effects of islet neogenesis associated protein depend on vascular endothelial growth factor gene expression modulated by hypoxia-inducible factor 1-alpha; Elsevier Science Inc; Peptides; 117; 170090; 7-2019
0196-9781
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://www.ncbi.nlm.nih.gov/pubmed/31121197
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.peptides.2019.05.002
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0196978119300622
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
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dc.publisher.none.fl_str_mv Elsevier Science Inc
publisher.none.fl_str_mv Elsevier Science Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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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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