Proposed mechanisms for oligonucleotide IMT504 induced diabetes reversion in a mouse model of immunodependent diabetes

Autores
Bianchi, Maria Silvia; Bianchi, Stefania; Hernando Insua, Andrés; Martinez, Leandro Marcelo; Lago, Néstor R.; Libertun, Carlos; Chasseing, Norma Alejandra; Montaner, Alejandro Daniel; Lux, Victoria Adela R.
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Type 1 diabetes (T1D) originates from autoimmune β-cell destruction. IMT504 is an immunomodulatory oligonucleotide that increases mesenchymal stem cells cloning capacity and reverts toxic diabetes in rats. Here we evaluated long-term (20 doses) and short-term (2-6 doses) effects of IMT504 (20 mg/kg/day, sc) in an immunodependent diabetes model: multiple low dose streptozotocin-injected BALB/c mice (40 mg/kg/day, i.p. for 5 consecutive days). We determined blood glucose, glucose tolerance, serum insulin, islet morphology, islet infiltration, serum cytokines, progenitor cell markers, immunomodulatory proteins, proliferation, apoptosis, and islet gene expression. Long-term results: IMT504 reduced glycemia, induced β-cell recovery and impaired islet infiltration. Short-term analysis: IMT504 induced early blood glucose decrease, infiltration inhibition, increased β-cell proliferation and decreased apoptosis, increased islet indoleamine 2,3-dioxygenase (IDO) expression, increased serum tumor necrosis factor and interleukin-6 (IL-6). IMT504 affected islet gene expression: Preproinsulin-2, Proglucagon, Somatostatin, Nestin, Regenerating gene-1 and C-X-C motif ligand-1 cytokine (Cxcl1) increased in islets from diabetic mice and were decreased by IMT504. IMT504 downregulated Platelet endothelial cell adhesion molecule-1 (Pecam1) in islets from control and diabetic mice, whereas it increased Regenerating gene-2 (Reg2) in islets of diabetic mice. The IMT504-induced increase in IL-6 and islet IDO expression, and decreased islet Pecam1 and Cxcl1 mRNA expression could participate in keeping leukocyte infiltration at bay, whereas upregulation of Reg2 may mediate β-cell regeneration. We conclude that IMT504 effectively reversed immunodependent diabetes in mice. Corroboration of these effects in a model of autoimmune diabetes more similar to human T1D could provide promising results for the treatment of this disease.
Fil: Bianchi, Maria Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Bianchi, Stefania. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Hernando Insua, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. Cesar Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología ; Argentina
Fil: Martinez, Leandro Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Lago, Néstor R.. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Libertun, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Chasseing, Norma Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Montaner, Alejandro Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. Cesar Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología ; Argentina
Fil: Lux, Victoria Adela R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Materia
Diabetes
Oligonucleotide
Im504
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/24032
Acceder
id CONICETDig_1109dc3d55771c84169bb54866d1fba7
oai_identifier_str oai:ri.conicet.gov.ar:11336/24032
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Proposed mechanisms for oligonucleotide IMT504 induced diabetes reversion in a mouse model of immunodependent diabetesBianchi, Maria SilviaBianchi, StefaniaHernando Insua, AndrésMartinez, Leandro MarceloLago, Néstor R.Libertun, CarlosChasseing, Norma AlejandraMontaner, Alejandro DanielLux, Victoria Adela R.DiabetesOligonucleotideIm504https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Type 1 diabetes (T1D) originates from autoimmune β-cell destruction. IMT504 is an immunomodulatory oligonucleotide that increases mesenchymal stem cells cloning capacity and reverts toxic diabetes in rats. Here we evaluated long-term (20 doses) and short-term (2-6 doses) effects of IMT504 (20 mg/kg/day, sc) in an immunodependent diabetes model: multiple low dose streptozotocin-injected BALB/c mice (40 mg/kg/day, i.p. for 5 consecutive days). We determined blood glucose, glucose tolerance, serum insulin, islet morphology, islet infiltration, serum cytokines, progenitor cell markers, immunomodulatory proteins, proliferation, apoptosis, and islet gene expression. Long-term results: IMT504 reduced glycemia, induced β-cell recovery and impaired islet infiltration. Short-term analysis: IMT504 induced early blood glucose decrease, infiltration inhibition, increased β-cell proliferation and decreased apoptosis, increased islet indoleamine 2,3-dioxygenase (IDO) expression, increased serum tumor necrosis factor and interleukin-6 (IL-6). IMT504 affected islet gene expression: Preproinsulin-2, Proglucagon, Somatostatin, Nestin, Regenerating gene-1 and C-X-C motif ligand-1 cytokine (Cxcl1) increased in islets from diabetic mice and were decreased by IMT504. IMT504 downregulated Platelet endothelial cell adhesion molecule-1 (Pecam1) in islets from control and diabetic mice, whereas it increased Regenerating gene-2 (Reg2) in islets of diabetic mice. The IMT504-induced increase in IL-6 and islet IDO expression, and decreased islet Pecam1 and Cxcl1 mRNA expression could participate in keeping leukocyte infiltration at bay, whereas upregulation of Reg2 may mediate β-cell regeneration. We conclude that IMT504 effectively reversed immunodependent diabetes in mice. Corroboration of these effects in a model of autoimmune diabetes more similar to human T1D could provide promising results for the treatment of this disease.Fil: Bianchi, Maria Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Bianchi, Stefania. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Hernando Insua, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. Cesar Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología ; ArgentinaFil: Martinez, Leandro Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Lago, Néstor R.. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Libertun, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Chasseing, Norma Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Montaner, Alejandro Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. Cesar Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología ; ArgentinaFil: Lux, Victoria Adela R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaAmerican Physiological Society2016-07-21info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/24032Bianchi, Maria Silvia; Bianchi, Stefania; Hernando Insua, Andrés; Martinez, Leandro Marcelo; Lago, Néstor R.; et al.; Proposed mechanisms for oligonucleotide IMT504 induced diabetes reversion in a mouse model of immunodependent diabetes; American Physiological Society; American Journal Of Physiology-endocrinology And Metabolism; 311; 2; 21-7-2016; E380-E3950193-18491522-1555CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1152/ajpendo.00104.2016info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:58:48Zoai:ri.conicet.gov.ar:11336/24032instacron: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:34982025-10-15 14:58:48.928CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Proposed mechanisms for oligonucleotide IMT504 induced diabetes reversion in a mouse model of immunodependent diabetes
title Proposed mechanisms for oligonucleotide IMT504 induced diabetes reversion in a mouse model of immunodependent diabetes
spellingShingle Proposed mechanisms for oligonucleotide IMT504 induced diabetes reversion in a mouse model of immunodependent diabetes
Bianchi, Maria Silvia
Diabetes
Oligonucleotide
Im504
title_short Proposed mechanisms for oligonucleotide IMT504 induced diabetes reversion in a mouse model of immunodependent diabetes
title_full Proposed mechanisms for oligonucleotide IMT504 induced diabetes reversion in a mouse model of immunodependent diabetes
title_fullStr Proposed mechanisms for oligonucleotide IMT504 induced diabetes reversion in a mouse model of immunodependent diabetes
title_full_unstemmed Proposed mechanisms for oligonucleotide IMT504 induced diabetes reversion in a mouse model of immunodependent diabetes
title_sort Proposed mechanisms for oligonucleotide IMT504 induced diabetes reversion in a mouse model of immunodependent diabetes
dc.creator.none.fl_str_mv Bianchi, Maria Silvia
Bianchi, Stefania
Hernando Insua, Andrés
Martinez, Leandro Marcelo
Lago, Néstor R.
Libertun, Carlos
Chasseing, Norma Alejandra
Montaner, Alejandro Daniel
Lux, Victoria Adela R.
author Bianchi, Maria Silvia
author_facet Bianchi, Maria Silvia
Bianchi, Stefania
Hernando Insua, Andrés
Martinez, Leandro Marcelo
Lago, Néstor R.
Libertun, Carlos
Chasseing, Norma Alejandra
Montaner, Alejandro Daniel
Lux, Victoria Adela R.
author_role author
author2 Bianchi, Stefania
Hernando Insua, Andrés
Martinez, Leandro Marcelo
Lago, Néstor R.
Libertun, Carlos
Chasseing, Norma Alejandra
Montaner, Alejandro Daniel
Lux, Victoria Adela R.
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Diabetes
Oligonucleotide
Im504
topic Diabetes
Oligonucleotide
Im504
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Type 1 diabetes (T1D) originates from autoimmune β-cell destruction. IMT504 is an immunomodulatory oligonucleotide that increases mesenchymal stem cells cloning capacity and reverts toxic diabetes in rats. Here we evaluated long-term (20 doses) and short-term (2-6 doses) effects of IMT504 (20 mg/kg/day, sc) in an immunodependent diabetes model: multiple low dose streptozotocin-injected BALB/c mice (40 mg/kg/day, i.p. for 5 consecutive days). We determined blood glucose, glucose tolerance, serum insulin, islet morphology, islet infiltration, serum cytokines, progenitor cell markers, immunomodulatory proteins, proliferation, apoptosis, and islet gene expression. Long-term results: IMT504 reduced glycemia, induced β-cell recovery and impaired islet infiltration. Short-term analysis: IMT504 induced early blood glucose decrease, infiltration inhibition, increased β-cell proliferation and decreased apoptosis, increased islet indoleamine 2,3-dioxygenase (IDO) expression, increased serum tumor necrosis factor and interleukin-6 (IL-6). IMT504 affected islet gene expression: Preproinsulin-2, Proglucagon, Somatostatin, Nestin, Regenerating gene-1 and C-X-C motif ligand-1 cytokine (Cxcl1) increased in islets from diabetic mice and were decreased by IMT504. IMT504 downregulated Platelet endothelial cell adhesion molecule-1 (Pecam1) in islets from control and diabetic mice, whereas it increased Regenerating gene-2 (Reg2) in islets of diabetic mice. The IMT504-induced increase in IL-6 and islet IDO expression, and decreased islet Pecam1 and Cxcl1 mRNA expression could participate in keeping leukocyte infiltration at bay, whereas upregulation of Reg2 may mediate β-cell regeneration. We conclude that IMT504 effectively reversed immunodependent diabetes in mice. Corroboration of these effects in a model of autoimmune diabetes more similar to human T1D could provide promising results for the treatment of this disease.
Fil: Bianchi, Maria Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Bianchi, Stefania. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Hernando Insua, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. Cesar Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología ; Argentina
Fil: Martinez, Leandro Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Lago, Néstor R.. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Libertun, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Chasseing, Norma Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Montaner, Alejandro Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. Cesar Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología ; Argentina
Fil: Lux, Victoria Adela R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
description Type 1 diabetes (T1D) originates from autoimmune β-cell destruction. IMT504 is an immunomodulatory oligonucleotide that increases mesenchymal stem cells cloning capacity and reverts toxic diabetes in rats. Here we evaluated long-term (20 doses) and short-term (2-6 doses) effects of IMT504 (20 mg/kg/day, sc) in an immunodependent diabetes model: multiple low dose streptozotocin-injected BALB/c mice (40 mg/kg/day, i.p. for 5 consecutive days). We determined blood glucose, glucose tolerance, serum insulin, islet morphology, islet infiltration, serum cytokines, progenitor cell markers, immunomodulatory proteins, proliferation, apoptosis, and islet gene expression. Long-term results: IMT504 reduced glycemia, induced β-cell recovery and impaired islet infiltration. Short-term analysis: IMT504 induced early blood glucose decrease, infiltration inhibition, increased β-cell proliferation and decreased apoptosis, increased islet indoleamine 2,3-dioxygenase (IDO) expression, increased serum tumor necrosis factor and interleukin-6 (IL-6). IMT504 affected islet gene expression: Preproinsulin-2, Proglucagon, Somatostatin, Nestin, Regenerating gene-1 and C-X-C motif ligand-1 cytokine (Cxcl1) increased in islets from diabetic mice and were decreased by IMT504. IMT504 downregulated Platelet endothelial cell adhesion molecule-1 (Pecam1) in islets from control and diabetic mice, whereas it increased Regenerating gene-2 (Reg2) in islets of diabetic mice. The IMT504-induced increase in IL-6 and islet IDO expression, and decreased islet Pecam1 and Cxcl1 mRNA expression could participate in keeping leukocyte infiltration at bay, whereas upregulation of Reg2 may mediate β-cell regeneration. We conclude that IMT504 effectively reversed immunodependent diabetes in mice. Corroboration of these effects in a model of autoimmune diabetes more similar to human T1D could provide promising results for the treatment of this disease.
publishDate 2016
dc.date.none.fl_str_mv 2016-07-21
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/11336/24032
Bianchi, Maria Silvia; Bianchi, Stefania; Hernando Insua, Andrés; Martinez, Leandro Marcelo; Lago, Néstor R.; et al.; Proposed mechanisms for oligonucleotide IMT504 induced diabetes reversion in a mouse model of immunodependent diabetes; American Physiological Society; American Journal Of Physiology-endocrinology And Metabolism; 311; 2; 21-7-2016; E380-E395
0193-1849
1522-1555
CONICET Digital
CONICET
url http://hdl.handle.net/11336/24032
identifier_str_mv Bianchi, Maria Silvia; Bianchi, Stefania; Hernando Insua, Andrés; Martinez, Leandro Marcelo; Lago, Néstor R.; et al.; Proposed mechanisms for oligonucleotide IMT504 induced diabetes reversion in a mouse model of immunodependent diabetes; American Physiological Society; American Journal Of Physiology-endocrinology And Metabolism; 311; 2; 21-7-2016; E380-E395
0193-1849
1522-1555
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1152/ajpendo.00104.2016
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Physiological Society
publisher.none.fl_str_mv American Physiological Society
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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score 13.22299

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