ATP-gated P2X3 receptors constitute a positive autocrine signal for insulin release in the human pancreatic β cell

M. Caroline Jacques-Silva, Mayrin Correa-Medina, Over Cabrera, Rayner Rodriguez-Diaz, Natalia Makeeva, Alberto Fachado, Juan Diez, Dora M. Berman, Norma S. Kenyon, Camillo Ricordi, Antonello Pileggi, R. Damaris Molano, Per Olof Berggren, Alejandro Caicedo

Research output: Contribution to journalArticle

87 Scopus citations

Abstract

Extracellular ATP has been proposed as a paracrine signal in rodent islets, but it is unclear what role ATP plays in human islets. We now show the presence of an ATP signaling pathway that enhances the human β cell's sensitivity and responsiveness to glucose fluctuations. By using in situ hybridization, RT-PCR, immunohistochemistry, and Western blotting as well as recordings of cytoplasmic-free Ca2+ concentration, [Ca2+]i, and hormone release in vitro, we show that human β cells express ionotropic ATP receptors of the P2X3 type and that activation of these receptors by ATP coreleased with insulin amplifies glucose-induced insulin secretion. Released ATP activates P2X3 receptors in the β-cell plasma membrane, resulting in increased [Ca2+]i and enhanced insulin secretion. Therefore, in human islets, released ATP forms a positive autocrine feedback loop that sensitizes the β cell's secretory machinery. This may explain how the human pancreatic β cell can respond so effectively to relatively modest changes in glucose concentration under physiological conditions in vivo.

Original languageEnglish (US)
Pages (from-to)6465-6470
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number14
DOIs
StatePublished - Apr 6 2010

    Fingerprint

Keywords

  • Extracellular ATP
  • Human pancreatic β cell
  • Insulin secretion
  • P2X receptor
  • Positive autocrine feedback

ASJC Scopus subject areas

  • General

Cite this