title: [Membrane fatty acid receptors in the β-cell: novel therapeutic targets for type 2 diabetes].
abstract: Glucose homeostasis requires a tight regulation of insulin secretion from pancreatic β-cells. Insulin release is chiefly stimulated by glucose, but also modulated by other nutrients, including long-chain fatty acids which potentiate glucose-induced insulin secretion. The discovery of G-protein coupled receptors activated by fatty acids (and other lipid derivatives) and expressed at the surface of various cell types, including β-cells, has added a new dimension to our understanding of the control of glucose homeostasis by fatty acids. Amongst these receptors, GPR40 and GPR119 have generated great interest as potential therapeutic targets to augment insulin secretion in type 2 diabetes. In fact, the promising results of a phase 2 clinical trial with a GPR40 agonist have provided a proof of concept for this therapeutic strategy. However, our understanding of the biology and pharmacology of these receptors remains incomplete.
authors.affiliation: Département de médecine de l'université de Montréal, Montréal H1W 4A4, Québec, Canada.
authors.forename: Arturo D
authors.initials: AD
authors.lastname: Mancini
authors.forename: Vincent
authors.initials: V
authors.lastname: Poitout
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005227:Fatty Acids / Q000502:physiology*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000737:chemistry* / Q000502:physiology; D011956:Receptors, Cell Surface / Q000032:analysis / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000032:analysis / Q000502:physiology*
chemical_list: D005227:Fatty Acids; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C473103:FFAR2 protein, human; C473034:FFAR1 protein, human; C106262:FFAR3 protein, human; C519853:FFAR4 protein, human; C519854:GPR119 protein, human