Alpha cells secrete acetylcholine as a non-neuronal paracrine signal priming beta cell function in humans

Rayner Rodriguez Diaz, Robin Dando, M. Caroline Jacques-Silva, Alberto Fachado, Judith Molina, Midhat H Abdulreda, Camillo Ricordi, Stephen D Roper, Per Olof Berggren, Diego A Caicedo-Vierkant

Research output: Contribution to journalArticle

145 Citations (Scopus)

Abstract

Acetylcholine is a neurotransmitter that has a major role in the function of the insulin-secreting pancreatic beta cell. Parasympathetic innervation of the endocrine pancreas, the islets of Langerhans, has been shown to provide cholinergic input to the beta cell in several species, but the role of autonomic innervation in human beta cell function is at present unclear. Here we show that, in contrast to the case in mouse islets, cholinergic innervation of human islets is sparse. Instead, we find that the alpha cells of human islets provide paracrine cholinergic input to surrounding endocrine cells. Human alpha cells express the vesicular acetylcholine transporter and release acetylcholine when stimulated with kainate or a lowering in glucose concentration. Acetylcholine secretion by alpha cells in turn sensitizes the beta cell response to increases in glucose concentration. Our results demonstrate that in human islets acetylcholine is a paracrine signal that primes the beta cell to respond optimally to subsequent increases in glucose concentration. Cholinergic signaling within islets represents a potential therapeutic target in diabetes, highlighting the relevance of this advance to future drug development.

Original languageEnglish
Pages (from-to)888-892
Number of pages5
JournalNature Medicine
Volume17
Issue number7
DOIs
StatePublished - Jul 1 2011

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Cholinergic Agents
Acetylcholine
Islets of Langerhans
Glucose
Vesicular Acetylcholine Transport Proteins
Cells
Insulin-Secreting Cells
Kainic Acid
Medical problems
Neurotransmitter Agents
Endocrine Cells
Insulin
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Alpha cells secrete acetylcholine as a non-neuronal paracrine signal priming beta cell function in humans. / Rodriguez Diaz, Rayner; Dando, Robin; Jacques-Silva, M. Caroline; Fachado, Alberto; Molina, Judith; Abdulreda, Midhat H; Ricordi, Camillo; Roper, Stephen D; Berggren, Per Olof; Caicedo-Vierkant, Diego A.

In: Nature Medicine, Vol. 17, No. 7, 01.07.2011, p. 888-892.

Research output: Contribution to journalArticle

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