Glucagon like peptide-1-induced glucose metabolism in differentiated human muscle satellite cells is attenuated by hyperglycemia.

<h4>Background</h4>Glucagon like peptide-1 (GLP-1) stimulates insulin secretion from the pancreas but also has extra-pancreatic effects. GLP-1 may stimulate glucose uptake in cultured muscle cells but the mechanism is not clearly defined. Furthermore, while the pancreatic effects of GLP-...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Charlotte J Green, Tora I Henriksen, Bente K Pedersen, Thomas P J Solomon
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/36c06a0a792045cbabbc70713ac261cc
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:36c06a0a792045cbabbc70713ac261cc
record_format	dspace
spelling	oai:doaj.org-article:36c06a0a792045cbabbc70713ac261cc2021-11-18T07:07:24ZGlucagon like peptide-1-induced glucose metabolism in differentiated human muscle satellite cells is attenuated by hyperglycemia.1932-620310.1371/journal.pone.0044284https://doaj.org/article/36c06a0a792045cbabbc70713ac261cc2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22937169/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Glucagon like peptide-1 (GLP-1) stimulates insulin secretion from the pancreas but also has extra-pancreatic effects. GLP-1 may stimulate glucose uptake in cultured muscle cells but the mechanism is not clearly defined. Furthermore, while the pancreatic effects of GLP-1 are glucose-dependent, the glucose-dependency of its extra-pancreatic effects has not been examined.<h4>Methods</h4>Skeletal muscle satellite cells isolated from young (22.5 ± 0.97 yr), lean (BMI 22.5 ± 0.6 kg/m(2)), healthy males were differentiated in media containing either 22.5 mM (high) or 5 mM (normal) glucose for 7 days in the absence or presence of insulin and/or various GLP-1 concentrations. Myocellular effects of GLP-1, insulin and glucose were assessed by western-blot, glucose uptake and glycogen synthesis.<h4>Results</h4>We firstly show that the GLP-1 receptor protein is expressed in differentiated human muscle satellite cells (myocytes). Secondly, we show that in 5 mM glucose media, exposure of myocytes to GLP-1 results in a dose dependent increase in glucose uptake, GLUT4 amount and subsequently glycogen synthesis in a PI3K dependent manner, independent of the insulin signaling cascade. Importantly, we provide evidence that differentiation of human satellite cells in hyperglycemic (22.5 mM glucose) conditions increases GLUT1 expression, and renders the cells insulin resistant and interestingly GLP-1 resistant in terms of glucose uptake and glycogen synthesis. Hyperglycemic conditions did not affect the ability of insulin to phosphorylate downstream targets, PKB or GSK3. Interestingly we show that at 5 mM glucose, GLP-1 increases GLUT4 protein levels and that this effect is abolished by hyperglycemia.<h4>Conclusions</h4>GLP-1 increases glucose uptake and glycogen synthesis into fully-differentiated human satellite cells in a PI3-K dependent mechanism potentially through increased GLUT4 protein levels. The latter occurs independently of the insulin signaling pathway. Attenuation of both GLP-1 and insulin-induced glucose metabolism by hyperglycemia is likely to occur downstream of PI3K.Charlotte J GreenTora I HenriksenBente K PedersenThomas P J SolomonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 8, p e44284 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Charlotte J Green Tora I Henriksen Bente K Pedersen Thomas P J Solomon Glucagon like peptide-1-induced glucose metabolism in differentiated human muscle satellite cells is attenuated by hyperglycemia.
description	<h4>Background</h4>Glucagon like peptide-1 (GLP-1) stimulates insulin secretion from the pancreas but also has extra-pancreatic effects. GLP-1 may stimulate glucose uptake in cultured muscle cells but the mechanism is not clearly defined. Furthermore, while the pancreatic effects of GLP-1 are glucose-dependent, the glucose-dependency of its extra-pancreatic effects has not been examined.<h4>Methods</h4>Skeletal muscle satellite cells isolated from young (22.5 ± 0.97 yr), lean (BMI 22.5 ± 0.6 kg/m(2)), healthy males were differentiated in media containing either 22.5 mM (high) or 5 mM (normal) glucose for 7 days in the absence or presence of insulin and/or various GLP-1 concentrations. Myocellular effects of GLP-1, insulin and glucose were assessed by western-blot, glucose uptake and glycogen synthesis.<h4>Results</h4>We firstly show that the GLP-1 receptor protein is expressed in differentiated human muscle satellite cells (myocytes). Secondly, we show that in 5 mM glucose media, exposure of myocytes to GLP-1 results in a dose dependent increase in glucose uptake, GLUT4 amount and subsequently glycogen synthesis in a PI3K dependent manner, independent of the insulin signaling cascade. Importantly, we provide evidence that differentiation of human satellite cells in hyperglycemic (22.5 mM glucose) conditions increases GLUT1 expression, and renders the cells insulin resistant and interestingly GLP-1 resistant in terms of glucose uptake and glycogen synthesis. Hyperglycemic conditions did not affect the ability of insulin to phosphorylate downstream targets, PKB or GSK3. Interestingly we show that at 5 mM glucose, GLP-1 increases GLUT4 protein levels and that this effect is abolished by hyperglycemia.<h4>Conclusions</h4>GLP-1 increases glucose uptake and glycogen synthesis into fully-differentiated human satellite cells in a PI3-K dependent mechanism potentially through increased GLUT4 protein levels. The latter occurs independently of the insulin signaling pathway. Attenuation of both GLP-1 and insulin-induced glucose metabolism by hyperglycemia is likely to occur downstream of PI3K.
format	article
author	Charlotte J Green Tora I Henriksen Bente K Pedersen Thomas P J Solomon
author_facet	Charlotte J Green Tora I Henriksen Bente K Pedersen Thomas P J Solomon
author_sort	Charlotte J Green
title	Glucagon like peptide-1-induced glucose metabolism in differentiated human muscle satellite cells is attenuated by hyperglycemia.
title_short	Glucagon like peptide-1-induced glucose metabolism in differentiated human muscle satellite cells is attenuated by hyperglycemia.
title_full	Glucagon like peptide-1-induced glucose metabolism in differentiated human muscle satellite cells is attenuated by hyperglycemia.
title_fullStr	Glucagon like peptide-1-induced glucose metabolism in differentiated human muscle satellite cells is attenuated by hyperglycemia.
title_full_unstemmed	Glucagon like peptide-1-induced glucose metabolism in differentiated human muscle satellite cells is attenuated by hyperglycemia.
title_sort	glucagon like peptide-1-induced glucose metabolism in differentiated human muscle satellite cells is attenuated by hyperglycemia.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/36c06a0a792045cbabbc70713ac261cc
work_keys_str_mv	AT charlottejgreen glucagonlikepeptide1inducedglucosemetabolismindifferentiatedhumanmusclesatellitecellsisattenuatedbyhyperglycemia AT toraihenriksen glucagonlikepeptide1inducedglucosemetabolismindifferentiatedhumanmusclesatellitecellsisattenuatedbyhyperglycemia AT bentekpedersen glucagonlikepeptide1inducedglucosemetabolismindifferentiatedhumanmusclesatellitecellsisattenuatedbyhyperglycemia AT thomaspjsolomon glucagonlikepeptide1inducedglucosemetabolismindifferentiatedhumanmusclesatellitecellsisattenuatedbyhyperglycemia
_version_	1718423909076828160

Glucagon like peptide-1-induced glucose metabolism in differentiated human muscle satellite cells is attenuated by hyperglycemia.

Ejemplares similares