Islet neogenesis-associated protein (INGAP): the role of its endogenous production as a positive modulator of insulin secretion

Autores
Flores, Luis Emilio; del Zotto, Hector Herminio; Fragapane, Florencia; Maiztegui, Barbara; Román, Carolina Lisi; Boschero, Antonio C.; Gagliardino, Juan Jose
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Islet neogenesis-associated protein (INGAP) is a peptide found in pancreatic exocrine-, duct- and islet- non-β-cells from normal hamsters. Its increase induced by either its exogenous administration or by the overexpression of its gene enhances β-cell secretory function and increases β-cell mass by a combination of stimulation of cell replication and islet neogenesis and reduction of β-cell apoptosis. We studied the potential modulatory role of endogenous INGAP in insulin secretion using two different experimental approaches. Hamster islets transfected with INGAP-small interfering RNA (INGAP-siRNA) were used to study glucose-stimulated insulin secretion (GSIS). In parallel, freshly isolated islets were incubated with high glucose and the same concentration of either a specific anti-INGAP rabbit serum or normal rabbit serum. INGAP-siRNA transfected islets reduced their INGAP mRNA and protein content by 35.1% and 47.2%, respectively whereas GSIS decreased by 25.8%. GSIS by transfected islets attained levels comparable to those recorded in control islets when INGAP pentadecapeptide (INGAP-PP) was added to the culture medium. INGAP antibody in the medium decreased significantly GSIS in a dose-dependent manner. These results indicate that endogenous INGAP plays a “physiological” positive modulatory role in insulin secretion, supporting its possible use in the treatment of prediabetes and Type 2 diabetes.
Fil: Flores, Luis Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico la Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentina. Universidad Nacional de La Plata; Argentina
Fil: del Zotto, Hector Herminio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico la Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentina. Universidad Nacional de La Plata; Argentina
Fil: Fragapane, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico la Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentina. Universidad Nacional de La Plata; Argentina
Fil: Maiztegui, Barbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico la Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentina. Universidad Nacional de La Plata; Argentina
Fil: Román, Carolina Lisi. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico la Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentina. Universidad Nacional de La Plata; Argentina
Fil: Boschero, Antonio C.. Universidade Estadual de Campinas; Brasil
Fil: Gagliardino, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico la Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentina. Universidad Nacional de La Plata; Argentina
Materia
Ingap
Insulin Secretion
Sirna
Hamsters
Isolated Islets
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:11336/10547

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oai_identifier_str oai:ri.conicet.gov.ar:11336/10547
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Islet neogenesis-associated protein (INGAP): the role of its endogenous production as a positive modulator of insulin secretionFlores, Luis Emiliodel Zotto, Hector HerminioFragapane, FlorenciaMaiztegui, BarbaraRomán, Carolina LisiBoschero, Antonio C.Gagliardino, Juan JoseIngapInsulin SecretionSirnaHamstersIsolated Isletshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Islet neogenesis-associated protein (INGAP) is a peptide found in pancreatic exocrine-, duct- and islet- non-β-cells from normal hamsters. Its increase induced by either its exogenous administration or by the overexpression of its gene enhances β-cell secretory function and increases β-cell mass by a combination of stimulation of cell replication and islet neogenesis and reduction of β-cell apoptosis. We studied the potential modulatory role of endogenous INGAP in insulin secretion using two different experimental approaches. Hamster islets transfected with INGAP-small interfering RNA (INGAP-siRNA) were used to study glucose-stimulated insulin secretion (GSIS). In parallel, freshly isolated islets were incubated with high glucose and the same concentration of either a specific anti-INGAP rabbit serum or normal rabbit serum. INGAP-siRNA transfected islets reduced their INGAP mRNA and protein content by 35.1% and 47.2%, respectively whereas GSIS decreased by 25.8%. GSIS by transfected islets attained levels comparable to those recorded in control islets when INGAP pentadecapeptide (INGAP-PP) was added to the culture medium. INGAP antibody in the medium decreased significantly GSIS in a dose-dependent manner. These results indicate that endogenous INGAP plays a “physiological” positive modulatory role in insulin secretion, supporting its possible use in the treatment of prediabetes and Type 2 diabetes.Fil: Flores, Luis Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico la Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentina. Universidad Nacional de La Plata; ArgentinaFil: del Zotto, Hector Herminio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico la Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentina. Universidad Nacional de La Plata; ArgentinaFil: Fragapane, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico la Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentina. Universidad Nacional de La Plata; ArgentinaFil: Maiztegui, Barbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico la Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentina. Universidad Nacional de La Plata; ArgentinaFil: Román, Carolina Lisi. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico la Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentina. Universidad Nacional de La Plata; ArgentinaFil: Boschero, Antonio C.. Universidade Estadual de Campinas; BrasilFil: Gagliardino, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico la Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentina. Universidad Nacional de La Plata; ArgentinaElsevier Science2014-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/10547Flores, Luis Emilio; del Zotto, Hector Herminio; Fragapane, Florencia; Maiztegui, Barbara; Román, Carolina Lisi; et al.; Islet neogenesis-associated protein (INGAP): the role of its endogenous production as a positive modulator of insulin secretion; Elsevier Science; Regulatory Peptides; 192-193; 8-2014; 30-340167-0115enginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.regpep.2014.08.003info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:57:29Zoai:ri.conicet.gov.ar:11336/10547instacron: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 09:57:29.535CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Islet neogenesis-associated protein (INGAP): the role of its endogenous production as a positive modulator of insulin secretion
title Islet neogenesis-associated protein (INGAP): the role of its endogenous production as a positive modulator of insulin secretion
spellingShingle Islet neogenesis-associated protein (INGAP): the role of its endogenous production as a positive modulator of insulin secretion
Flores, Luis Emilio
Ingap
Insulin Secretion
Sirna
Hamsters
Isolated Islets
title_short Islet neogenesis-associated protein (INGAP): the role of its endogenous production as a positive modulator of insulin secretion
title_full Islet neogenesis-associated protein (INGAP): the role of its endogenous production as a positive modulator of insulin secretion
title_fullStr Islet neogenesis-associated protein (INGAP): the role of its endogenous production as a positive modulator of insulin secretion
title_full_unstemmed Islet neogenesis-associated protein (INGAP): the role of its endogenous production as a positive modulator of insulin secretion
title_sort Islet neogenesis-associated protein (INGAP): the role of its endogenous production as a positive modulator of insulin secretion
dc.creator.none.fl_str_mv Flores, Luis Emilio
del Zotto, Hector Herminio
Fragapane, Florencia
Maiztegui, Barbara
Román, Carolina Lisi
Boschero, Antonio C.
Gagliardino, Juan Jose
author Flores, Luis Emilio
author_facet Flores, Luis Emilio
del Zotto, Hector Herminio
Fragapane, Florencia
Maiztegui, Barbara
Román, Carolina Lisi
Boschero, Antonio C.
Gagliardino, Juan Jose
author_role author
author2 del Zotto, Hector Herminio
Fragapane, Florencia
Maiztegui, Barbara
Román, Carolina Lisi
Boschero, Antonio C.
Gagliardino, Juan Jose
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Ingap
Insulin Secretion
Sirna
Hamsters
Isolated Islets
topic Ingap
Insulin Secretion
Sirna
Hamsters
Isolated Islets
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Islet neogenesis-associated protein (INGAP) is a peptide found in pancreatic exocrine-, duct- and islet- non-β-cells from normal hamsters. Its increase induced by either its exogenous administration or by the overexpression of its gene enhances β-cell secretory function and increases β-cell mass by a combination of stimulation of cell replication and islet neogenesis and reduction of β-cell apoptosis. We studied the potential modulatory role of endogenous INGAP in insulin secretion using two different experimental approaches. Hamster islets transfected with INGAP-small interfering RNA (INGAP-siRNA) were used to study glucose-stimulated insulin secretion (GSIS). In parallel, freshly isolated islets were incubated with high glucose and the same concentration of either a specific anti-INGAP rabbit serum or normal rabbit serum. INGAP-siRNA transfected islets reduced their INGAP mRNA and protein content by 35.1% and 47.2%, respectively whereas GSIS decreased by 25.8%. GSIS by transfected islets attained levels comparable to those recorded in control islets when INGAP pentadecapeptide (INGAP-PP) was added to the culture medium. INGAP antibody in the medium decreased significantly GSIS in a dose-dependent manner. These results indicate that endogenous INGAP plays a “physiological” positive modulatory role in insulin secretion, supporting its possible use in the treatment of prediabetes and Type 2 diabetes.
Fil: Flores, Luis Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico la Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentina. Universidad Nacional de La Plata; Argentina
Fil: del Zotto, Hector Herminio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico la Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentina. Universidad Nacional de La Plata; Argentina
Fil: Fragapane, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico la Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentina. Universidad Nacional de La Plata; Argentina
Fil: Maiztegui, Barbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico la Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentina. Universidad Nacional de La Plata; Argentina
Fil: Román, Carolina Lisi. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico la Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentina. Universidad Nacional de La Plata; Argentina
Fil: Boschero, Antonio C.. Universidade Estadual de Campinas; Brasil
Fil: Gagliardino, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico la Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentina. Universidad Nacional de La Plata; Argentina
description Islet neogenesis-associated protein (INGAP) is a peptide found in pancreatic exocrine-, duct- and islet- non-β-cells from normal hamsters. Its increase induced by either its exogenous administration or by the overexpression of its gene enhances β-cell secretory function and increases β-cell mass by a combination of stimulation of cell replication and islet neogenesis and reduction of β-cell apoptosis. We studied the potential modulatory role of endogenous INGAP in insulin secretion using two different experimental approaches. Hamster islets transfected with INGAP-small interfering RNA (INGAP-siRNA) were used to study glucose-stimulated insulin secretion (GSIS). In parallel, freshly isolated islets were incubated with high glucose and the same concentration of either a specific anti-INGAP rabbit serum or normal rabbit serum. INGAP-siRNA transfected islets reduced their INGAP mRNA and protein content by 35.1% and 47.2%, respectively whereas GSIS decreased by 25.8%. GSIS by transfected islets attained levels comparable to those recorded in control islets when INGAP pentadecapeptide (INGAP-PP) was added to the culture medium. INGAP antibody in the medium decreased significantly GSIS in a dose-dependent manner. These results indicate that endogenous INGAP plays a “physiological” positive modulatory role in insulin secretion, supporting its possible use in the treatment of prediabetes and Type 2 diabetes.
publishDate 2014
dc.date.none.fl_str_mv 2014-08
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/11336/10547
Flores, Luis Emilio; del Zotto, Hector Herminio; Fragapane, Florencia; Maiztegui, Barbara; Román, Carolina Lisi; et al.; Islet neogenesis-associated protein (INGAP): the role of its endogenous production as a positive modulator of insulin secretion; Elsevier Science; Regulatory Peptides; 192-193; 8-2014; 30-34
0167-0115
url http://hdl.handle.net/11336/10547
identifier_str_mv Flores, Luis Emilio; del Zotto, Hector Herminio; Fragapane, Florencia; Maiztegui, Barbara; Román, Carolina Lisi; et al.; Islet neogenesis-associated protein (INGAP): the role of its endogenous production as a positive modulator of insulin secretion; Elsevier Science; Regulatory Peptides; 192-193; 8-2014; 30-34
0167-0115
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.regpep.2014.08.003
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
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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