The metabolic relevance of the UDP-glucose receptor P2Y14
Introduction: The G protein-coupled receptor P2Y14 is activated by UDP, UDP-glucose and other UDP-sugars. Northern blot and qPCR analyses showed that P2Y14 is widely expressed in human and mouse tissues. Most studies focus on P2Y14 presence in immune cells, suggesting a physiological relevance in immune and inflammatory responses. Although the highest expression is found in the gastrointestinal (GI) tract and adipose tissue little is known about the metabolic relevance of P2Y14.
Aim: To clarify the physiological role of P2Y14 with specific focus on energy homeostasis we use a P2Y14-deficient mouse model.
Methods: P2Y14-knockout (KO) mouse strain expresses the bacterial LacZ reporter gene to monitor the physiological expression pattern of P2Y14. KO and wild-type (WT) mice were compared in numerous functional tests including glucose- and insulin tolerance tests under standard and western-type diets.
Results: We found that P2Y14 is mainly expressed in a subpopulation of smooth muscle cells of the GI tract, pancreas, salivary glands, blood vessels, lung and uterus. Among other phenotypical differences KO mice showed a significantly impaired glucose tolerance following oral and intraperitoneal glucose application. By performing insulin tolerance and insulin secretion tests we could pinpoint this phenotype to a reduced insulin release from pancreatic islets lacking P2Y14.
Conclusion: Our study revealed P2Y14 as a new modulator of proper insulin secretion. Further, transcriptome analysis of pancreatic islets will contribute to understand the intracellular signal transduction pathways of the P2Y14-receptor.