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

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

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Abstract

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

Item Type:	Article (Journal)
Additional Information:	4312/64800
Uncontrolled Keywords:	Oleoyl-lysophosphatidylinositol, glucagon like peptide-1, CREB,
Subjects:	Q Science > QH Natural history > QH301 Biology R Medicine > RM Therapeutics. Pharmacology > RM283 Endocrinotheraphy R Medicine > RM Therapeutics. Pharmacology > RM300 Drugs and their action
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Nursing
Depositing User:	Syamsul Ahmad Arifin
Date Deposited:	27 Jul 2018 14:42
Last Modified:	24 Jan 2019 11:14
URI:	http://irep.iium.edu.my/id/eprint/64800

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