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Biochim Biophys Acta Mol Cell Biol Lipids. 2018 Sep;1863(9):1132-1141. doi: 10.1016/j.bbalip.2018.06.007. Epub 2018 Jun 5.

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

Author information

1
Centre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, E1 2AT London, United Kingdom; Department of Basic Medical Science for Nursing, Kulliyyah of Nursing, IIUM, Bandar Indera Mahkota, 25200 Kuantan, Pahang, Malaysia.
2
Metabolic Signalling Group, School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia 6102, Australia.
3
Cell and Molecular Metabolism Laboratory, School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia 6102, Australia.
4
Laboratory for Molecular Pharmacology, Department for Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
5
Centre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, E1 2AT London, United Kingdom.
6
Centre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, E1 2AT London, United Kingdom; Metabolic Signalling Group, School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia 6102, Australia. Electronic address: marco.falasca@curtin.edu.au.

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.

KEYWORDS:

GPR119; GPR55; Glucagon-like peptide-1 (GLP-1); L-cells; Lysophosphatidylinositol (LPI); Mixed colonic preparation

PMID:
29883799
DOI:
10.1016/j.bbalip.2018.06.007
[Indexed for MEDLINE]

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