GLP-1 and GLP-2 as Ying and Yang of Intestinal Lipoprotein Production: Evidence for predominance of GLP-2-stimulated postprandial lipemia in normal and insulin Resistant States

Autores
Hein, Gustavo Juan; Baker, Chris; Hsieh, Joanne; Farr, Sara; Khosrow, Adeli
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The glucagon-like peptides (GLP-1 and GLP-2) are processed from the proglucagon polypeptide and secreted in equimolar amounts but have opposite effects on chylomicron (CM) production, with GLP-1 significantly reducing and GLP-2 increasing postprandial chylomicronemia. In the current study, we evaluated the apparent paradoxical roles of GLP-1 and GLP-2 under physiological conditions in the Syrian golden hamster, a model with close similarity to humans in terms of lipoprotein metabolism. A short (30-min) intravenous infusion of GLP-2 resulted in a marked increase in postprandial apolipoprotein B48 (apoB48) and triglyceride (TG) levels in the TG-rich lipoprotein (TRL) fraction, whereas GLP-1 infusion decreased lipid absorption and levels of TRL-TG and apoB48. GLP-1 and GLP-2 coinfusion resulted in net increased lipid absorption and an increase in TRL-TG and apoB48. However, prolonged (120-min) coinfusion of GLP-1 and GLP-2 decreased postprandial lipemia. Blocking dipeptidyl peptidase-4 activity resulted in decreased postprandial lipemia. Interestingly, fructose-fed, insulin-resistant hamsters showed a more pronounced response, including possible hypersensitivity to GLP-2 or reduced sensitivity to GLP-1. In conclusion, under normal physiological conditions, the actions of GLP-2 predominate; however, when GLP-1 activity is sustained, the hypolipidemic action of GLP-1 predominates. Pharmacological inhibition of GLP-1 degradation tips the balance toward an inhibitory effect on intestinal production of atherogenic CM particles.
Fil: Hein, Gustavo Juan. University Of Toronto. Hospital For Sick Children; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Cs.veterinarias. Instituto de Ciencias Veterinarias del Litoral; Argentina
Fil: Baker, Chris. University Of Toronto. Hospital For Sick Children; Canadá
Fil: Hsieh, Joanne. University Of Toronto. Hospital For Sick Children; Canadá
Fil: Farr, Sara. University Of Toronto. Hospital For Sick Children; Canadá
Fil: Khosrow, Adeli. University Of Toronto. Hospital For Sick Children; Canadá
Materia
Apolipoprotein B
Chylomicrons
Glucagon-Like Peptide
Dipeptidyl Peptidase-4
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:11336/16339
Acceder
id CONICETDig_8c86e0459c12514a99de332a4bfbcca7
oai_identifier_str oai:ri.conicet.gov.ar:11336/16339
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling GLP-1 and GLP-2 as Ying and Yang of Intestinal Lipoprotein Production: Evidence for predominance of GLP-2-stimulated postprandial lipemia in normal and insulin Resistant StatesHein, Gustavo JuanBaker, ChrisHsieh, JoanneFarr, SaraKhosrow, AdeliApolipoprotein BChylomicronsGlucagon-Like PeptideDipeptidyl Peptidase-4https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The glucagon-like peptides (GLP-1 and GLP-2) are processed from the proglucagon polypeptide and secreted in equimolar amounts but have opposite effects on chylomicron (CM) production, with GLP-1 significantly reducing and GLP-2 increasing postprandial chylomicronemia. In the current study, we evaluated the apparent paradoxical roles of GLP-1 and GLP-2 under physiological conditions in the Syrian golden hamster, a model with close similarity to humans in terms of lipoprotein metabolism. A short (30-min) intravenous infusion of GLP-2 resulted in a marked increase in postprandial apolipoprotein B48 (apoB48) and triglyceride (TG) levels in the TG-rich lipoprotein (TRL) fraction, whereas GLP-1 infusion decreased lipid absorption and levels of TRL-TG and apoB48. GLP-1 and GLP-2 coinfusion resulted in net increased lipid absorption and an increase in TRL-TG and apoB48. However, prolonged (120-min) coinfusion of GLP-1 and GLP-2 decreased postprandial lipemia. Blocking dipeptidyl peptidase-4 activity resulted in decreased postprandial lipemia. Interestingly, fructose-fed, insulin-resistant hamsters showed a more pronounced response, including possible hypersensitivity to GLP-2 or reduced sensitivity to GLP-1. In conclusion, under normal physiological conditions, the actions of GLP-2 predominate; however, when GLP-1 activity is sustained, the hypolipidemic action of GLP-1 predominates. Pharmacological inhibition of GLP-1 degradation tips the balance toward an inhibitory effect on intestinal production of atherogenic CM particles.Fil: Hein, Gustavo Juan. University Of Toronto. Hospital For Sick Children; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Cs.veterinarias. Instituto de Ciencias Veterinarias del Litoral; ArgentinaFil: Baker, Chris. University Of Toronto. Hospital For Sick Children; CanadáFil: Hsieh, Joanne. University Of Toronto. Hospital For Sick Children; CanadáFil: Farr, Sara. University Of Toronto. Hospital For Sick Children; CanadáFil: Khosrow, Adeli. University Of Toronto. Hospital For Sick Children; CanadáAmerican Diabetes Association2013-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/16339Hein, Gustavo Juan; Baker, Chris; Hsieh, Joanne; Farr, Sara; Khosrow, Adeli; GLP-1 and GLP-2 as Ying and Yang of Intestinal Lipoprotein Production: Evidence for predominance of GLP-2-stimulated postprandial lipemia in normal and insulin Resistant States; American Diabetes Association; Diabetes; 62; 2; 6-2013; 373-3810012-1797enginfo:eu-repo/semantics/altIdentifier/url/http://diabetes.diabetesjournals.org/content/early/2012/09/19/db12-0202.abstractinfo:eu-repo/semantics/altIdentifier/doi/10.2337/db12-0202info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-05T09:44:35Zoai:ri.conicet.gov.ar:11336/16339instacron: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:34982025-11-05 09:44:35.907CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv GLP-1 and GLP-2 as Ying and Yang of Intestinal Lipoprotein Production: Evidence for predominance of GLP-2-stimulated postprandial lipemia in normal and insulin Resistant States
title GLP-1 and GLP-2 as Ying and Yang of Intestinal Lipoprotein Production: Evidence for predominance of GLP-2-stimulated postprandial lipemia in normal and insulin Resistant States
spellingShingle GLP-1 and GLP-2 as Ying and Yang of Intestinal Lipoprotein Production: Evidence for predominance of GLP-2-stimulated postprandial lipemia in normal and insulin Resistant States
Hein, Gustavo Juan
Apolipoprotein B
Chylomicrons
Glucagon-Like Peptide
Dipeptidyl Peptidase-4
title_short GLP-1 and GLP-2 as Ying and Yang of Intestinal Lipoprotein Production: Evidence for predominance of GLP-2-stimulated postprandial lipemia in normal and insulin Resistant States
title_full GLP-1 and GLP-2 as Ying and Yang of Intestinal Lipoprotein Production: Evidence for predominance of GLP-2-stimulated postprandial lipemia in normal and insulin Resistant States
title_fullStr GLP-1 and GLP-2 as Ying and Yang of Intestinal Lipoprotein Production: Evidence for predominance of GLP-2-stimulated postprandial lipemia in normal and insulin Resistant States
title_full_unstemmed GLP-1 and GLP-2 as Ying and Yang of Intestinal Lipoprotein Production: Evidence for predominance of GLP-2-stimulated postprandial lipemia in normal and insulin Resistant States
title_sort GLP-1 and GLP-2 as Ying and Yang of Intestinal Lipoprotein Production: Evidence for predominance of GLP-2-stimulated postprandial lipemia in normal and insulin Resistant States
dc.creator.none.fl_str_mv Hein, Gustavo Juan
Baker, Chris
Hsieh, Joanne
Farr, Sara
Khosrow, Adeli
author Hein, Gustavo Juan
author_facet Hein, Gustavo Juan
Baker, Chris
Hsieh, Joanne
Farr, Sara
Khosrow, Adeli
author_role author
author2 Baker, Chris
Hsieh, Joanne
Farr, Sara
Khosrow, Adeli
author2_role author
author
author
author
dc.subject.none.fl_str_mv Apolipoprotein B
Chylomicrons
Glucagon-Like Peptide
Dipeptidyl Peptidase-4
topic Apolipoprotein B
Chylomicrons
Glucagon-Like Peptide
Dipeptidyl Peptidase-4
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The glucagon-like peptides (GLP-1 and GLP-2) are processed from the proglucagon polypeptide and secreted in equimolar amounts but have opposite effects on chylomicron (CM) production, with GLP-1 significantly reducing and GLP-2 increasing postprandial chylomicronemia. In the current study, we evaluated the apparent paradoxical roles of GLP-1 and GLP-2 under physiological conditions in the Syrian golden hamster, a model with close similarity to humans in terms of lipoprotein metabolism. A short (30-min) intravenous infusion of GLP-2 resulted in a marked increase in postprandial apolipoprotein B48 (apoB48) and triglyceride (TG) levels in the TG-rich lipoprotein (TRL) fraction, whereas GLP-1 infusion decreased lipid absorption and levels of TRL-TG and apoB48. GLP-1 and GLP-2 coinfusion resulted in net increased lipid absorption and an increase in TRL-TG and apoB48. However, prolonged (120-min) coinfusion of GLP-1 and GLP-2 decreased postprandial lipemia. Blocking dipeptidyl peptidase-4 activity resulted in decreased postprandial lipemia. Interestingly, fructose-fed, insulin-resistant hamsters showed a more pronounced response, including possible hypersensitivity to GLP-2 or reduced sensitivity to GLP-1. In conclusion, under normal physiological conditions, the actions of GLP-2 predominate; however, when GLP-1 activity is sustained, the hypolipidemic action of GLP-1 predominates. Pharmacological inhibition of GLP-1 degradation tips the balance toward an inhibitory effect on intestinal production of atherogenic CM particles.
Fil: Hein, Gustavo Juan. University Of Toronto. Hospital For Sick Children; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Cs.veterinarias. Instituto de Ciencias Veterinarias del Litoral; Argentina
Fil: Baker, Chris. University Of Toronto. Hospital For Sick Children; Canadá
Fil: Hsieh, Joanne. University Of Toronto. Hospital For Sick Children; Canadá
Fil: Farr, Sara. University Of Toronto. Hospital For Sick Children; Canadá
Fil: Khosrow, Adeli. University Of Toronto. Hospital For Sick Children; Canadá
description The glucagon-like peptides (GLP-1 and GLP-2) are processed from the proglucagon polypeptide and secreted in equimolar amounts but have opposite effects on chylomicron (CM) production, with GLP-1 significantly reducing and GLP-2 increasing postprandial chylomicronemia. In the current study, we evaluated the apparent paradoxical roles of GLP-1 and GLP-2 under physiological conditions in the Syrian golden hamster, a model with close similarity to humans in terms of lipoprotein metabolism. A short (30-min) intravenous infusion of GLP-2 resulted in a marked increase in postprandial apolipoprotein B48 (apoB48) and triglyceride (TG) levels in the TG-rich lipoprotein (TRL) fraction, whereas GLP-1 infusion decreased lipid absorption and levels of TRL-TG and apoB48. GLP-1 and GLP-2 coinfusion resulted in net increased lipid absorption and an increase in TRL-TG and apoB48. However, prolonged (120-min) coinfusion of GLP-1 and GLP-2 decreased postprandial lipemia. Blocking dipeptidyl peptidase-4 activity resulted in decreased postprandial lipemia. Interestingly, fructose-fed, insulin-resistant hamsters showed a more pronounced response, including possible hypersensitivity to GLP-2 or reduced sensitivity to GLP-1. In conclusion, under normal physiological conditions, the actions of GLP-2 predominate; however, when GLP-1 activity is sustained, the hypolipidemic action of GLP-1 predominates. Pharmacological inhibition of GLP-1 degradation tips the balance toward an inhibitory effect on intestinal production of atherogenic CM particles.
publishDate 2013
dc.date.none.fl_str_mv 2013-06
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/11336/16339
Hein, Gustavo Juan; Baker, Chris; Hsieh, Joanne; Farr, Sara; Khosrow, Adeli; GLP-1 and GLP-2 as Ying and Yang of Intestinal Lipoprotein Production: Evidence for predominance of GLP-2-stimulated postprandial lipemia in normal and insulin Resistant States; American Diabetes Association; Diabetes; 62; 2; 6-2013; 373-381
0012-1797
url http://hdl.handle.net/11336/16339
identifier_str_mv Hein, Gustavo Juan; Baker, Chris; Hsieh, Joanne; Farr, Sara; Khosrow, Adeli; GLP-1 and GLP-2 as Ying and Yang of Intestinal Lipoprotein Production: Evidence for predominance of GLP-2-stimulated postprandial lipemia in normal and insulin Resistant States; American Diabetes Association; Diabetes; 62; 2; 6-2013; 373-381
0012-1797
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://diabetes.diabetesjournals.org/content/early/2012/09/19/db12-0202.abstract
info:eu-repo/semantics/altIdentifier/doi/10.2337/db12-0202
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
dc.publisher.none.fl_str_mv American Diabetes Association
publisher.none.fl_str_mv American Diabetes Association
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
_version_ 1847977058969321472
score 13.121305

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