Oleoyl-lysophosphatidylinositol enhances glucagon-like peptide-1 secretion from enteroendocrine L-cells through GPR119
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Oleoyl-lysophosphatidylinositol enhances glucagon-like peptide-1 secretion from enteroendocrine L-cells through GPR119. / Arifin, Syamsul A.; Paternoster, Silvano; Carlessi, Rodrigo; Casari, Ilaria; Ekberg, Jeppe Hvidtfeldt; Maffucci, Tania; Newsholme, Philip; Rosenkilde, Mette M.; Falasca, Marco.
In: B B A - Molecular and Cell Biology of Lipids, Vol. 1863, No. 9, 2018, p. 1132-1141.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Oleoyl-lysophosphatidylinositol enhances glucagon-like peptide-1 secretion from enteroendocrine L-cells through GPR119
AU - Arifin, Syamsul A.
AU - Paternoster, Silvano
AU - Carlessi, Rodrigo
AU - Casari, Ilaria
AU - Ekberg, Jeppe Hvidtfeldt
AU - Maffucci, Tania
AU - Newsholme, Philip
AU - Rosenkilde, Mette M.
AU - Falasca, Marco
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - Lysophosphatidylinositol (LPI)
KW - Glucagon-like peptide-1 (GLP-1)
KW - GPR119
KW - GPR55
KW - L-cells
KW - Mixed colonic preparation
U2 - 10.1016/j.bbalip.2018.06.007
DO - 10.1016/j.bbalip.2018.06.007
M3 - Journal article
C2 - 29883799
VL - 1863
SP - 1132
EP - 1141
JO - B B A - Molecular and Cell Biology of Lipids
JF - B B A - Molecular and Cell Biology of Lipids
SN - 1388-1981
IS - 9
ER -
ID: 212954733