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Horm Metab Res 2008; 40(11): 827-830
DOI: 10.1055/s-0028-1082050
Short Communication

© Georg Thieme Verlag KG Stuttgart · New York

Human Pancreatic Islets Express the Purinergic P2Y11 and P2Y12 Receptors

L. Lugo-Garcia 1 , B. Nadal 2 , R. Gomis 2 , P. Petit 1 , R. Gross 1 , A. D. Lajoix 1
  • 1Montpellier 1 University, CNRS UMR 5232, Centre for Pharmacology and Innovation in Diabetes, Faculty of Pharmacy, Montpellier, France
  • 2Endocrinology and Diabetes Unit, Department of Medicine, Hospital Clínic/IDIBAPS, University of Barcelona, Barcelona, Spain
Further Information

Publication History

received 25.10.2007

accepted 14.04.2008

Publication Date:
22 August 2008 (online)

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Introduction

Extracellular adenine nucleotides and their analogues are well-known to stimulate pancreatic β-cell function [1], despite recent evidence for a possible inhibitory function [2]. Attempts to identify the different P2Y receptor subtypes coupled to specific transduction pathways on pancreatic endocrine cells were mainly based on a pharmacological approach using agonists and/or antagonists more specific for a particular receptor subtype. Recent RT-PCR and Western blotting studies from our laboratory [3] point out that pancreatic β-cells, in addition to the previously described P2Y4 receptor subtype [4], also express the P2Y1, P2Y2, P2Y6, and P2Y12 isoforms.

At present, eight human P2Y receptor subtypes are known that can phylogenetically and structurally be divided into two subgroups. The first one includes P2Y1, P2Y2, P2Y4, P2Y6, P2Y11 and the second one P2Y12, P2Y13, P2Y14 [5] [6]. Concerning their transduction pathways, P2Y1, P2Y2, P2Y4, P2Y6 are coupled to phospholipase C and intracellular Ca2+mobilization. The P2Y11 receptor, upon stimulation by ATP, leads to a rise in both cAMP and IP3. The structure and ligand binding characteristics of this less studied receptor subtype have recently been deduced from computational modeling and mutational analysis [7]. Furthermore, it has been proposed as a new target for prevention of acute myocardial infarction [8] and interestingly found to associate functionally with P2Y1, promoting its internalization [9]. Concerning the second subgroup, P2Y12, P2Y13, P2Y14 are known to be coupled to Gi/o proteins.

G protein-coupled receptors (GPCR) are important targets for the development of antidiabetic drugs and, in pancreatic islets, they are mainly coupled to adenylate cyclase and to phospholipase C [10]. Three main factors prompted us to investigate the possible presence of P2Y11 and P2Y12 receptors as future antidiabetic targets in human pancreatic islets and to determine their cellular localization: 1. An increase in cAMP is responsible for the glucose-dependant insulinotropic effect of GLP-1, the most promising antidiabetic drug presently in development; 2. P2Y agonists induce a glucose-dependent increase in insulin secretion in human pancreatic islets [11]; and 3. The cAMP/PKA pathway intervenes in ATPαS insulin secretory effect in rat islets [12].

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Correspondence

A.D. Lajoix

CNRS UMR 5232

Faculté de Pharmacie

15 avenue Charles Flahault

BP 14491

34093 Montpellier Cedex 5

France

Phone: +33/467/92 65 29

Fax: +33/467/92 45 53

Email: anne-dominique.lajoix@univ-montp1.fr

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