title: The G protein-coupled receptor P2Y14 influences insulin release and smooth muscle function in mice.
abstract: UDP sugars were identified as extracellular signaling molecules, assigning a new function to these compounds in addition to their well defined role in intracellular substrate metabolism and storage. Previously regarded as an orphan receptor, the G protein-coupled receptor P2Y14 (GPR105) was found to bind extracellular UDP and UDP sugars. Little is known about the physiological functions of this G protein-coupled receptor. To study its physiological role, we used a gene-deficient mouse strain expressing the bacterial LacZ reporter gene to monitor the physiological expression pattern of P2Y14. We found that P2Y14 is mainly expressed in pancreas and salivary glands and in subpopulations of smooth muscle cells of the gastrointestinal tract, blood vessels, lung, and uterus. Among other phenotypical differences, knock-out mice showed a significantly impaired glucose tolerance following oral and intraperitoneal glucose application. An unchanged insulin tolerance suggested altered pancreatic islet function. Transcriptome analysis of pancreatic islets showed that P2Y14 deficiency significantly changed expression of components involved in insulin secretion. Insulin secretion tests revealed a reduced insulin release from P2Y14-deficient islets, highlighting P2Y14 as a new modulator of proper insulin secretion.
authors.affiliation: From the Institute of Biochemistry, Integrated Research and Treatment Center for Adiposity Diseases.
authors.forename: Jaroslawna
authors.initials: J
authors.lastname: Meister
authors.affiliation: From the Institute of Biochemistry.
authors.forename: Diana
authors.initials: D
authors.lastname: Le Duc
authors.affiliation: Institute of Anatomy, and.
authors.forename: Albert
authors.initials: A
authors.lastname: Ricken
authors.affiliation: Institute of Laboratory Medicine, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Burkhardt
authors.affiliation: Institute of Laboratory Medicine, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Thiery
authors.affiliation: the Institute of Veterinary Physiology, Faculty of Veterinary Medicine, University of Leipzig, 04109 Leipzig, Germany.
authors.forename: Helga
authors.initials: H
authors.lastname: Pfannkuche
authors.affiliation: the Department of Environmental Immunology, UFZ-Helmholtz Centre for Environmental Research Leipzig-Halle, 04318 Leipzig, Germany, the Department of Dermatology, Venerology and Allergology, Leipzig University Medical Center, 04109 Leipzig, Germany, and.
authors.forename: Tobias
authors.initials: T
authors.lastname: Polte
authors.affiliation: Takeda Cambridge Ltd., Cambridge CB4 0PZ, United Kingdom.
authors.forename: Johannes
authors.initials: J
authors.lastname: Grosse
authors.affiliation: From the Institute of Biochemistry, schoberg@medizin.uni-leipzig.de.
authors.forename: Torsten
authors.initials: T
authors.lastname: Schöneberg
authors.affiliation: From the Institute of Biochemistry, Integrated Research and Treatment Center for Adiposity Diseases.
authors.forename: Angela
authors.initials: A
authors.lastname: Schulz
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D005746:Gastric Emptying; D018149:Glucose Intolerance; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009130:Muscle, Smooth / Q000502:physiology*; D016133:Polymerase Chain Reaction; D058470:Receptors, Purinergic P2Y / Q000235:genetics / Q000502:physiology*
chemical_list: D017931:DNA Primers; D007328:Insulin; C509795:P2ry14 protein, mouse; D058470:Receptors, Purinergic P2Y
keywords: G Protein-coupled Receptor (GPCR); Gene Knockout; Glucose Metabolism; Pancreatic Islet; Signal Transduction