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Title (Primary) The G protein-coupled receptor P2Y14 influences insulin release and smooth muscle function in mice
Author Meister, J.; Le Duc, D.; Ricken, A.; Burkhardt, R.; Thiery, J.; Pfannkuche, H.; Polte, T.; Grosse, J.; Schöneberg, T.; Schulz, A.;
Journal Journal of Biological Chemistry
Year 2014
Department IMMU;
Volume 289
Language englisch;
POF III (all) F11;
Keywords G protein-coupled receptor (GPCR); gene knockout; glucose metabolism; pancreatic islet; signal transduction
UFZ wide themes RU3;
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 (GPCR) P2Y14 (GPR105) was found to bind extracellular UDP and UDP-sugars. Little is known about the physiological functions of this GPCR. To study its physiological role we used a gene-deficient (KO) 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 KO 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.
ID 15019
Persistent UFZ Identifier http://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=15019
Meister, J., Le Duc, D., Ricken, A., Burkhardt, R., Thiery, J., Pfannkuche, H., Polte, T., Grosse, J., Schöneberg, T., Schulz, A. (2014):
The G protein-coupled receptor P2Y14 influences insulin release and smooth muscle function in mice
J. Biol. Chem. 289 , 23353 - 23366