title: Anti-hyperglycemic activity of a TGR5 agonist isolated from Olea europaea.
abstract: Olive tree (Olea europeaea) leaves are well known for their effect on metabolism in particular as a traditional anti-diabetic and anti-hypertensive herbal drug. These properties are until now only attributed to oleuropein, the major secoiridoid of olive leaves. Here we describe the isolation and the identification of another constituent implicated in the anti-diabetic effect of this plant, i.e. oleanolic acid. We show that this triterpene is an agonist for TGR5, a member of G-protein coupled receptor activated by bile acids and which mediates some of their various cellular and physiological effect. Oleanolic acid lowers serum glucose and insulin levels in mice fed with a high fat diet and it enhances glucose tolerance. Our data suggest that both oleuropein and oleanolic acid are involved in the anti-diabetic effect of olive leaves and further emphasize the potential role of TGR5 agonists to improve metabolic disorders.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/Université Louis Pasteur, 67404 Illkirch, France.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sato
authors.forename: Cédric
authors.initials: C
authors.lastname: Genet
authors.forename: Axelle
authors.initials: A
authors.lastname: Strehle
authors.forename: Charles
authors.initials: C
authors.lastname: Thomas
authors.forename: Annelise
authors.initials: A
authors.lastname: Lobstein
authors.forename: Alain
authors.initials: A
authors.lastname: Wagner
authors.forename: Charles
authors.initials: C
authors.lastname: Mioskowski
authors.forename: Johan
authors.initials: J
authors.lastname: Auwerx
authors.forename: Régis
authors.initials: R
authors.lastname: Saladin
mesh_terms: D000284:Administration, Oral; D000818:Animals; D006943:Hyperglycemia / Q000188:drug therapy* / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D031658:Olea / Q000378:metabolism*; D010936:Plant Extracts / Q000008:administration & dosage*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism*; D016896:Treatment Outcome