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 Berman-Weinberg, Norma S Kenyon, Camillo Ricordi, Antonello Pileggi, Ruth Molano, Per Olof Berggren, Diego A Caicedo-Vierkant

Research output: Contribution to journalArticle

86 Citations (Scopus)

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
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

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Purinergic P2X3 Receptors
Adenosine Triphosphate
Insulin
Glucose
Cell Membrane
Purinergic P2 Receptors
In Situ Hybridization
Rodentia
Western Blotting
Immunohistochemistry
Hormones
Polymerase Chain Reaction

Keywords

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

ASJC Scopus subject areas

  • General

Cite this

ATP-gated P2X3 receptors constitute a positive autocrine signal for insulin release in the human pancreatic β cell. / Jacques-Silva, M. Caroline; Correa-Medina, Mayrin; Cabrera, Over; Rodriguez Diaz, Rayner; Makeeva, Natalia; Fachado, Alberto; Diez, Juan; Berman-Weinberg, Dora; Kenyon, Norma S; Ricordi, Camillo; Pileggi, Antonello; Molano, Ruth; Berggren, Per Olof; Caicedo-Vierkant, Diego A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 14, 06.04.2010, p. 6465-6470.

Research output: Contribution to journalArticle

Jacques-Silva, M. Caroline ; Correa-Medina, Mayrin ; Cabrera, Over ; Rodriguez Diaz, Rayner ; Makeeva, Natalia ; Fachado, Alberto ; Diez, Juan ; Berman-Weinberg, Dora ; Kenyon, Norma S ; Ricordi, Camillo ; Pileggi, Antonello ; Molano, Ruth ; Berggren, Per Olof ; Caicedo-Vierkant, Diego A. / ATP-gated P2X3 receptors constitute a positive autocrine signal for insulin release in the human pancreatic β cell. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 14. pp. 6465-6470.
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