title: Glucose transporter 2 expression is down regulated following P2X7 activation in enterocytes.
abstract: With the diabetes epidemic affecting the world population, there is an increasing demand for means to regulate glycemia. Dietary glucose is first absorbed by the intestine before entering the blood stream. Thus, the regulation of glucose absorption by intestinal epithelial cells (IECs) could represent a way to regulate glycemia. Among the molecules involved in glycemia homeostasis, extracellular ATP, a paracrine signaling molecule, was reported to induce insulin secretion from pancreatic β cells by activating P2Y and P2X receptors. In rat's jejunum, P2X7 expression was previously immunolocalized to the apex of villi, where it has been suspected to play a role in apoptosis. However, using an antibody recognizing the receptor extracellular domain and thus most of the P2X7 isoforms, we showed that expression of this receptor is apparent in the top two-thirds of villi. These data suggest a different role for this receptor in IECs. Using the non-cancerous IEC-6 cells and differentiated Caco-2 cells, glucose transport was reduced by more than 30% following P2X7 stimulation. This effect on glucose transport was not due to P2X7-induced cell apoptosis, but rather was the consequence of glucose transporter 2 (Glut2)'s internalization. The signaling pathway leading to P2X7-dependent Glut2 internalization involved the calcium-independent activation of phospholipase Cγ1 (PLCγ1), PKCδ, and PKD1. Although the complete mechanism regulating Glut2 internalization following P2X7 activation is not fully understood, modulation of P2X7 receptor activation could represent an interesting approach to regulate intestinal glucose absorption.
authors.affiliation: Department of Anatomy and Cell Biology, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Bourzac
authors.forename: Karine
authors.initials: K
authors.lastname: L'Ériger
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Larrivée
authors.forename: Guillaume
authors.initials: G
authors.lastname: Arguin
authors.forename: Maude S
authors.initials: MS
authors.lastname: Bilodeau
authors.forename: Jana
authors.initials: J
authors.lastname: Stankova
authors.forename: Fernand-Pierre
authors.initials: FP
authors.lastname: Gendron
mesh_terms: D000818:Animals; D002460:Cell Line; D015536:Down-Regulation; D020895:Enterocytes / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D051273:Glucose Transporter Type 2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011493:Protein Kinase C / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000378:metabolism; D058911:Purinergic P2X Receptor Agonists / Q000494:pharmacology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D058486:Receptors, Purinergic P2X7 / Q000235:genetics / Q000378:metabolism*
chemical_list: D051273:Glucose Transporter Type 2; D058911:Purinergic P2X Receptor Agonists; D034741:RNA, Small Interfering; D058486:Receptors, Purinergic P2X7; C495680:SLC2A2 protein, human; C495683:Slc2a2 protein, rat; C089212:protein kinase D; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D005947:Glucose