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...
| Main Authors: | , , , , , , , , |
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| Format: | Journal Article |
| Published: |
2018
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| Online Access: | http://hdl.handle.net/20.500.11937/68737 |
| _version_ | 1848761877728854016 |
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| author | Arifin, S. Paternoster, Silvano Carlessi, Rodrigo Casari, Ilaria Ekberg, J. Maffucci, T. Newsholme, Philip Rosenkilde, M. Falasca, Marco |
| author_facet | Arifin, S. Paternoster, Silvano Carlessi, Rodrigo Casari, Ilaria Ekberg, J. Maffucci, T. Newsholme, Philip Rosenkilde, M. Falasca, Marco |
| author_sort | Arifin, S. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| 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. |
| first_indexed | 2025-11-14T10:38:39Z |
| format | Journal Article |
| id | curtin-20.500.11937-68737 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:38:39Z |
| publishDate | 2018 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-687372018-09-06T03:37:14Z Oleoyl-lysophosphatidylinositol enhances glucagon-like peptide-1 secretion from enteroendocrine L-cells through GPR119. Arifin, S. Paternoster, Silvano Carlessi, Rodrigo Casari, Ilaria Ekberg, J. Maffucci, T. Newsholme, Philip Rosenkilde, M. Falasca, Marco 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. 2018 Journal Article http://hdl.handle.net/20.500.11937/68737 10.1016/j.bbalip.2018.06.007 restricted |
| spellingShingle | Arifin, S. Paternoster, Silvano Carlessi, Rodrigo Casari, Ilaria Ekberg, J. Maffucci, T. Newsholme, Philip Rosenkilde, M. Falasca, Marco Oleoyl-lysophosphatidylinositol enhances glucagon-like peptide-1 secretion from enteroendocrine L-cells through GPR119. |
| title | 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_short | 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. |
| url | http://hdl.handle.net/20.500.11937/68737 |