Oleoyl-lysophosphatidylinositol enhances glucagon-like peptide-1 secretion from enteroendocrine L-cells through GPR119

The gastrointestinal tract is increasingly viewed as critical in controlling glucose metabolism, because of its role in secreting multiple glucoregulatory hormones, such as glucagon like peptide-1 (GLP-1). Here we investigate the molecular pathways behind the GLP-1- and insulin-secreting capabilitie...

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Main Authors: Ahmad Arifin, Syamsul, Paternoster, Silvano, Carlessi, Rodrigo, Casari, Ilaria, Ekberge, Jeppe Hvidtfeldt, Maffucci, Tania, Newsholme, Philip, Rosenkilde, Mette M., Falasca, Marco
Format: Article
Language:English
English
English
Published: Elsevier 2018
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Online Access:http://irep.iium.edu.my/64800/
http://irep.iium.edu.my/64800/
http://irep.iium.edu.my/64800/
http://irep.iium.edu.my/64800/7/64800_Oleoyl-lysophosphatidylinositol%20enhances_SCOPUS.pdf
http://irep.iium.edu.my/64800/13/64800_Oleoyl-lysophosphatidylinositol%20enhances.pdf
http://irep.iium.edu.my/64800/19/64800_Oleoyl-lysophosphatidylinositol%20enhances%20_WoS.pdf
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spelling iium-648002019-01-24T03:14:14Z http://irep.iium.edu.my/64800/ Oleoyl-lysophosphatidylinositol enhances glucagon-like peptide-1 secretion from enteroendocrine L-cells through GPR119 Ahmad Arifin, Syamsul Paternoster, Silvano Carlessi, Rodrigo Casari, Ilaria Ekberge, Jeppe Hvidtfeldt Maffucci, Tania Newsholme, Philip Rosenkilde, Mette M. Falasca, Marco QH301 Biology RM283 Endocrinotheraphy RM300 Drugs and their action The gastrointestinal tract is increasingly viewed as critical in controlling glucose metabolism, because of its role in secreting multiple glucoregulatory hormones, such as glucagon like peptide-1 (GLP-1). Here we investigate the molecular pathways behind the GLP-1- and insulin-secreting capabilities of a novel GPR119 agonist, Oleoyl-lysophosphatidylinositol (Oleoyl-LPI). Oleoyl-LPI is the only LPI species able to potently stimulate the release of GLP-1 in vitro, from murine and human L-cells, and ex-vivo from murine colonic primary cell preparations. Here we show that Oleoyl-LPI mediates GLP-1 secretion through GPR119 as this activity is ablated in cells lacking GPR119 and in colonic primary cell preparation from GPR119-/- mice. Similarly, Oleoyl-LPI-mediated insulin secretion is impaired in islets isolated from GPR119-/- mice. On the other hand, GLP-1 secretion is not impaired in cells lacking GPR55 in vitro or in colonic primary cell preparation from GPR55-/- mice. We therefore conclude that GPR119 is the Oleoyl-LPI receptor, upstream of ERK1/2 and cAMP/PKA/CREB pathways, where primarily ERK1/2 is required for GLP-1 secretion, while CREB activation appears dispensable Elsevier 2018-06-05 Article PeerReviewed application/pdf en http://irep.iium.edu.my/64800/7/64800_Oleoyl-lysophosphatidylinositol%20enhances_SCOPUS.pdf application/pdf en http://irep.iium.edu.my/64800/13/64800_Oleoyl-lysophosphatidylinositol%20enhances.pdf application/pdf en http://irep.iium.edu.my/64800/19/64800_Oleoyl-lysophosphatidylinositol%20enhances%20_WoS.pdf Ahmad Arifin, Syamsul and Paternoster, Silvano and Carlessi, Rodrigo and Casari, Ilaria and Ekberge, Jeppe Hvidtfeldt and Maffucci, Tania and Newsholme, Philip and Rosenkilde, Mette M. and Falasca, Marco (2018) Oleoyl-lysophosphatidylinositol enhances glucagon-like peptide-1 secretion from enteroendocrine L-cells through GPR119. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, 1863 (9). pp. 1132-1141. ISSN 1388-1981 https://www.sciencedirect.com/science/article/pii/S1388198118301288?via%3Dihub 10.1016/j.bbalip.2018.06.007
repository_type Digital Repository
institution_category Local University
institution International Islamic University Malaysia
building IIUM Repository
collection Online Access
language English
English
English
topic QH301 Biology
RM283 Endocrinotheraphy
RM300 Drugs and their action
spellingShingle QH301 Biology
RM283 Endocrinotheraphy
RM300 Drugs and their action
Ahmad Arifin, Syamsul
Paternoster, Silvano
Carlessi, Rodrigo
Casari, Ilaria
Ekberge, Jeppe Hvidtfeldt
Maffucci, Tania
Newsholme, Philip
Rosenkilde, Mette M.
Falasca, Marco
Oleoyl-lysophosphatidylinositol enhances glucagon-like peptide-1 secretion from enteroendocrine L-cells through GPR119
description The gastrointestinal tract is increasingly viewed as critical in controlling glucose metabolism, because of its role in secreting multiple glucoregulatory hormones, such as glucagon like peptide-1 (GLP-1). Here we investigate the molecular pathways behind the GLP-1- and insulin-secreting capabilities of a novel GPR119 agonist, Oleoyl-lysophosphatidylinositol (Oleoyl-LPI). Oleoyl-LPI is the only LPI species able to potently stimulate the release of GLP-1 in vitro, from murine and human L-cells, and ex-vivo from murine colonic primary cell preparations. Here we show that Oleoyl-LPI mediates GLP-1 secretion through GPR119 as this activity is ablated in cells lacking GPR119 and in colonic primary cell preparation from GPR119-/- mice. Similarly, Oleoyl-LPI-mediated insulin secretion is impaired in islets isolated from GPR119-/- mice. On the other hand, GLP-1 secretion is not impaired in cells lacking GPR55 in vitro or in colonic primary cell preparation from GPR55-/- mice. We therefore conclude that GPR119 is the Oleoyl-LPI receptor, upstream of ERK1/2 and cAMP/PKA/CREB pathways, where primarily ERK1/2 is required for GLP-1 secretion, while CREB activation appears dispensable
format Article
author Ahmad Arifin, Syamsul
Paternoster, Silvano
Carlessi, Rodrigo
Casari, Ilaria
Ekberge, Jeppe Hvidtfeldt
Maffucci, Tania
Newsholme, Philip
Rosenkilde, Mette M.
Falasca, Marco
author_facet Ahmad Arifin, Syamsul
Paternoster, Silvano
Carlessi, Rodrigo
Casari, Ilaria
Ekberge, Jeppe Hvidtfeldt
Maffucci, Tania
Newsholme, Philip
Rosenkilde, Mette M.
Falasca, Marco
author_sort Ahmad Arifin, Syamsul
title Oleoyl-lysophosphatidylinositol enhances glucagon-like peptide-1 secretion from enteroendocrine L-cells through GPR119
title_short Oleoyl-lysophosphatidylinositol enhances glucagon-like peptide-1 secretion from enteroendocrine L-cells through GPR119
title_full Oleoyl-lysophosphatidylinositol enhances glucagon-like peptide-1 secretion from enteroendocrine L-cells through GPR119
title_fullStr Oleoyl-lysophosphatidylinositol enhances glucagon-like peptide-1 secretion from enteroendocrine L-cells through GPR119
title_full_unstemmed Oleoyl-lysophosphatidylinositol enhances glucagon-like peptide-1 secretion from enteroendocrine L-cells through GPR119
title_sort oleoyl-lysophosphatidylinositol enhances glucagon-like peptide-1 secretion from enteroendocrine l-cells through gpr119
publisher Elsevier
publishDate 2018
url http://irep.iium.edu.my/64800/
http://irep.iium.edu.my/64800/
http://irep.iium.edu.my/64800/
http://irep.iium.edu.my/64800/7/64800_Oleoyl-lysophosphatidylinositol%20enhances_SCOPUS.pdf
http://irep.iium.edu.my/64800/13/64800_Oleoyl-lysophosphatidylinositol%20enhances.pdf
http://irep.iium.edu.my/64800/19/64800_Oleoyl-lysophosphatidylinositol%20enhances%20_WoS.pdf
first_indexed 2023-09-18T21:31:58Z
last_indexed 2023-09-18T21:31:58Z
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