Control of liver glucokinase activity: a potential new target for incretin hormones?

Autores
Francini, Flavio; Massa, Maria Laura; Polo, Monica Patricia; Villagarcía, Hernán Gonzalo; Castro, María Cecilia; Gagliardino, Juan Jose
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We tested the exendin-4 and des-fluoro-sitagliptin effects on fructose-induced increase in liver glucokinase activity in rats with impaired glucose tolerance and the exendin-4 effect on glucokinase activity in HepG2 cells incubated with fructose in the presence/absence of exendin-9-39. After 3 weeks of in vivo fructose administration we measured: (1) serum glucose, insulin and triglyceride levels; (2) liver and HepG2 cells glucokinase activity and (3) liver glucokinase and 6-phosphofructo-2-kinase/fructose-2,6- biphosphatase mRNA and protein levels. Fructose fed rats had: hypertriglyceridemia, hyperinsulinemia and high liver glucokinase activity (mainly located in the cytosolic fraction) together with higher glucokinase and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase mRNA and protein concentrations compared to control rats. Co-administration of either exendin-4 or des-fluoro-sitagliptin prevented serum and liver changes except glucokinase protein expression. Exendin-4 also prevented fructoseinduced increase in glucokinase activity in cultured HepG2 cells, effect blunted by co-incubation with exendin-9-36. In conclusion exendin-4/des-fluro-sitagliptin prevented fructose-induced effect on glucokinase activity, mainly affecting enzyme activity modulators. Exendin 9-39 blunted in vitro protective exendin-4 effect onglucokinase activity,thus suggesting a direct effect ofthe later onhepatocytes through GLP-1 receptor. Alterations of glucokinase activity modulators could play a role in the pathogenesis of liver dysfunction, becoming a potential new treatment target for GLP-1 receptor agonists
Fil: Francini, Flavio. 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: Massa, Maria Laura. 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: Polo, Monica Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Investigaciones Bioquímicas de La Plata; Argentina. Universidad Nacional de La Plata; Argentina
Fil: Villagarcía, Hernán Gonzalo. 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: Castro, María Cecilia. 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: 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
Incretins
Liver Glucokinase
Exendin-4
Pfk-2
Prediabetes
Glp-1
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:11336/10462
Acceder
id CONICETDig_59d90a837cabeb95812267fb63e2c420
oai_identifier_str oai:ri.conicet.gov.ar:11336/10462
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Control of liver glucokinase activity: a potential new target for incretin hormones?Francini, FlavioMassa, Maria LauraPolo, Monica PatriciaVillagarcía, Hernán GonzaloCastro, María CeciliaGagliardino, Juan JoseIncretinsLiver GlucokinaseExendin-4Pfk-2PrediabetesGlp-1https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3We tested the exendin-4 and des-fluoro-sitagliptin effects on fructose-induced increase in liver glucokinase activity in rats with impaired glucose tolerance and the exendin-4 effect on glucokinase activity in HepG2 cells incubated with fructose in the presence/absence of exendin-9-39. After 3 weeks of in vivo fructose administration we measured: (1) serum glucose, insulin and triglyceride levels; (2) liver and HepG2 cells glucokinase activity and (3) liver glucokinase and 6-phosphofructo-2-kinase/fructose-2,6- biphosphatase mRNA and protein levels. Fructose fed rats had: hypertriglyceridemia, hyperinsulinemia and high liver glucokinase activity (mainly located in the cytosolic fraction) together with higher glucokinase and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase mRNA and protein concentrations compared to control rats. Co-administration of either exendin-4 or des-fluoro-sitagliptin prevented serum and liver changes except glucokinase protein expression. Exendin-4 also prevented fructoseinduced increase in glucokinase activity in cultured HepG2 cells, effect blunted by co-incubation with exendin-9-36. In conclusion exendin-4/des-fluro-sitagliptin prevented fructose-induced effect on glucokinase activity, mainly affecting enzyme activity modulators. Exendin 9-39 blunted in vitro protective exendin-4 effect onglucokinase activity,thus suggesting a direct effect ofthe later onhepatocytes through GLP-1 receptor. Alterations of glucokinase activity modulators could play a role in the pathogenesis of liver dysfunction, becoming a potential new treatment target for GLP-1 receptor agonistsFil: Francini, Flavio. 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: Massa, Maria Laura. 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: Polo, Monica Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Investigaciones Bioquímicas de La Plata; Argentina. Universidad Nacional de La Plata; ArgentinaFil: Villagarcía, Hernán Gonzalo. 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: Castro, María Cecilia. 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: 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 Science Inc2015-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/10462Francini, Flavio; Massa, Maria Laura; Polo, Monica Patricia; Villagarcía, Hernán Gonzalo; Castro, María Cecilia; et al.; Control of liver glucokinase activity: a potential new target for incretin hormones?; Elsevier Science Inc; Peptides; 74; 12-2015; 57-630196-9781enginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.peptides.2015.10.006info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/26524624info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:24:23Zoai:ri.conicet.gov.ar:11336/10462instacron: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 10:24:24.201CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Control of liver glucokinase activity: a potential new target for incretin hormones?
title Control of liver glucokinase activity: a potential new target for incretin hormones?
spellingShingle Control of liver glucokinase activity: a potential new target for incretin hormones?
Francini, Flavio
Incretins
Liver Glucokinase
Exendin-4
Pfk-2
Prediabetes
Glp-1
title_short Control of liver glucokinase activity: a potential new target for incretin hormones?
title_full Control of liver glucokinase activity: a potential new target for incretin hormones?
title_fullStr Control of liver glucokinase activity: a potential new target for incretin hormones?
title_full_unstemmed Control of liver glucokinase activity: a potential new target for incretin hormones?
title_sort Control of liver glucokinase activity: a potential new target for incretin hormones?
dc.creator.none.fl_str_mv Francini, Flavio
Massa, Maria Laura
Polo, Monica Patricia
Villagarcía, Hernán Gonzalo
Castro, María Cecilia
Gagliardino, Juan Jose
author Francini, Flavio
author_facet Francini, Flavio
Massa, Maria Laura
Polo, Monica Patricia
Villagarcía, Hernán Gonzalo
Castro, María Cecilia
Gagliardino, Juan Jose
author_role author
author2 Massa, Maria Laura
Polo, Monica Patricia
Villagarcía, Hernán Gonzalo
Castro, María Cecilia
Gagliardino, Juan Jose
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Incretins
Liver Glucokinase
Exendin-4
Pfk-2
Prediabetes
Glp-1
topic Incretins
Liver Glucokinase
Exendin-4
Pfk-2
Prediabetes
Glp-1
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv We tested the exendin-4 and des-fluoro-sitagliptin effects on fructose-induced increase in liver glucokinase activity in rats with impaired glucose tolerance and the exendin-4 effect on glucokinase activity in HepG2 cells incubated with fructose in the presence/absence of exendin-9-39. After 3 weeks of in vivo fructose administration we measured: (1) serum glucose, insulin and triglyceride levels; (2) liver and HepG2 cells glucokinase activity and (3) liver glucokinase and 6-phosphofructo-2-kinase/fructose-2,6- biphosphatase mRNA and protein levels. Fructose fed rats had: hypertriglyceridemia, hyperinsulinemia and high liver glucokinase activity (mainly located in the cytosolic fraction) together with higher glucokinase and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase mRNA and protein concentrations compared to control rats. Co-administration of either exendin-4 or des-fluoro-sitagliptin prevented serum and liver changes except glucokinase protein expression. Exendin-4 also prevented fructoseinduced increase in glucokinase activity in cultured HepG2 cells, effect blunted by co-incubation with exendin-9-36. In conclusion exendin-4/des-fluro-sitagliptin prevented fructose-induced effect on glucokinase activity, mainly affecting enzyme activity modulators. Exendin 9-39 blunted in vitro protective exendin-4 effect onglucokinase activity,thus suggesting a direct effect ofthe later onhepatocytes through GLP-1 receptor. Alterations of glucokinase activity modulators could play a role in the pathogenesis of liver dysfunction, becoming a potential new treatment target for GLP-1 receptor agonists
Fil: Francini, Flavio. 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: Massa, Maria Laura. 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: Polo, Monica Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Investigaciones Bioquímicas de La Plata; Argentina. Universidad Nacional de La Plata; Argentina
Fil: Villagarcía, Hernán Gonzalo. 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: Castro, María Cecilia. 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: 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 We tested the exendin-4 and des-fluoro-sitagliptin effects on fructose-induced increase in liver glucokinase activity in rats with impaired glucose tolerance and the exendin-4 effect on glucokinase activity in HepG2 cells incubated with fructose in the presence/absence of exendin-9-39. After 3 weeks of in vivo fructose administration we measured: (1) serum glucose, insulin and triglyceride levels; (2) liver and HepG2 cells glucokinase activity and (3) liver glucokinase and 6-phosphofructo-2-kinase/fructose-2,6- biphosphatase mRNA and protein levels. Fructose fed rats had: hypertriglyceridemia, hyperinsulinemia and high liver glucokinase activity (mainly located in the cytosolic fraction) together with higher glucokinase and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase mRNA and protein concentrations compared to control rats. Co-administration of either exendin-4 or des-fluoro-sitagliptin prevented serum and liver changes except glucokinase protein expression. Exendin-4 also prevented fructoseinduced increase in glucokinase activity in cultured HepG2 cells, effect blunted by co-incubation with exendin-9-36. In conclusion exendin-4/des-fluro-sitagliptin prevented fructose-induced effect on glucokinase activity, mainly affecting enzyme activity modulators. Exendin 9-39 blunted in vitro protective exendin-4 effect onglucokinase activity,thus suggesting a direct effect ofthe later onhepatocytes through GLP-1 receptor. Alterations of glucokinase activity modulators could play a role in the pathogenesis of liver dysfunction, becoming a potential new treatment target for GLP-1 receptor agonists
publishDate 2015
dc.date.none.fl_str_mv 2015-12
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/11336/10462
Francini, Flavio; Massa, Maria Laura; Polo, Monica Patricia; Villagarcía, Hernán Gonzalo; Castro, María Cecilia; et al.; Control of liver glucokinase activity: a potential new target for incretin hormones?; Elsevier Science Inc; Peptides; 74; 12-2015; 57-63
0196-9781
url http://hdl.handle.net/11336/10462
identifier_str_mv Francini, Flavio; Massa, Maria Laura; Polo, Monica Patricia; Villagarcía, Hernán Gonzalo; Castro, María Cecilia; et al.; Control of liver glucokinase activity: a potential new target for incretin hormones?; Elsevier Science Inc; Peptides; 74; 12-2015; 57-63
0196-9781
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.peptides.2015.10.006
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/26524624
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 Elsevier Science Inc
publisher.none.fl_str_mv Elsevier Science Inc
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 13.070432

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