Abstract
In intestinal epithelial cells (IEC), it was reported that the activation of the P2X7 receptor leads to the internalization of the glucose transporter GLUT2, which is accompanied by a reduction of IEC capacity to transport glucose. In this study, we used P2rx7−/− mice to decipher P2X7 functions in intestinal glucose transport and to evaluate the impacts on metabolism. Immunohistochemistry analyses revealed the presence of GLUT2 at the apical domain of P2rx7−/− jejunum enterocytes. Positron emission tomography and biodistribution studies demonstrated that glucose was more efficiently delivered to the circulation of knockout animals. These findings correlated with increase blood glucose, insulin, triglycerides and cholesterol levels. In fact, P2rx7−/− mice had increased serum triglyceride and cholesterol levels and displayed glucose intolerance and resistance to insulin. Finally, P2rx7−/− mice developed a hepatic steatosis characterized by a reduction of Acaca, Acacb, Fasn and Acox1 mRNA expression, as well as for ACC and FAS protein expression. Our study suggests that P2X7 could play a central role in metabolic diseases.
Highlights
Adenosine 5′-triphosphate (ATP) is secreted in the extracellular environment where it acts as a signaling molecule[1]
The presence of apical GLUT2 was accompanied by a significant augmentation in the concentration of blood glucose measured in 12-week-old knockout mice as compared to wild-type littermates (Fig. 1H)
The reduction in the level of [18F]-FDG in the proximal small intestine of knockout animals and increase in blood, suggest that glucose is rapidly absorbed by enterocytes and transported to the blood stream, supporting the idea that the P2X7 receptor is involved in the regulation of glucose entries as we previously showed in vitro[4]
Summary
Adenosine 5′-triphosphate (ATP) is secreted in the extracellular environment where it acts as a signaling molecule[1]. Other studies suggested that apical GLUT2 might be required to accommodate the important concentration of luminal glucose in postprandial conditions[19,20,21] Despite this debate about the presence and function of GLUT2 at the IEC apical compartment, GLUT2 is required for glucose export to the blood stream, and as such represent an interesting target to control glycaemia. In this context, we previously showed that the stimulation of the P2X7 receptor initiated the internalization of GLUT2 in IEC. We determined that knockout animals were suffering from symptoms mimicking human metabolic diseases, including hepatic steatosis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
