Control of insulin secretion by cholinergic signaling in the human pancreatic islet

Judith Molina, Rayner Rodriguez Diaz, Alberto Fachado, M. Caroline Jacques-Silva, Per Olof Berggren, Diego A Caicedo-Vierkant

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Acetylcholine regulates hormone secretion from the pancreatic islet and is thus crucial for glucose homeo-stasis. Little is known, however, about acetylcholine (cholinergic) signaling in the human islet. We recently reported that in the human islet, acetylcholine is primarily a paracrine signal released from α-cells rather than primarily a neural signal as in rodent islets. In this study, we demonstrate that the effects acetylcholine produces in the human islet are different and more complex than expected from studies conducted on cell lines and rodent islets. We found that endogenous acetylcho-line not only stimulates the insulin-secreting β-cell via the muscarinic acetylcholine receptors M3 and M5, but also the somatostatin-secreting d-cell via M1 receptors. Because somatostatin is a strong inhibitor of insulin secretion, we hypothesized that cholinergic input to the d-cell indirectly regulates β-cell function. Indeed, when all muscarinic signaling was blocked, somatostatin secretion decreased and insulin secretion unexpectedly increased, suggesting a reduced inhibitory input to β-cells. Endogenous cholinergic signaling therefore provides direct stimulatory and indirect inhibitory input to β-cells to regulate insulin secretion from the human islet.

Original languageEnglish
Pages (from-to)2714-2726
Number of pages13
JournalDiabetes
Volume63
Issue number8
DOIs
StatePublished - Jan 1 2014

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Islets of Langerhans
Cholinergic Agents
Acetylcholine
Insulin
Somatostatin
Muscarinic M5 Receptors
Rodentia
Muscarinic M3 Receptors
Somatostatin-Secreting Cells
Insulin-Secreting Cells
Muscarinic Receptors
Hormones
Glucose
Cell Line

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Control of insulin secretion by cholinergic signaling in the human pancreatic islet. / Molina, Judith; Rodriguez Diaz, Rayner; Fachado, Alberto; Jacques-Silva, M. Caroline; Berggren, Per Olof; Caicedo-Vierkant, Diego A.

In: Diabetes, Vol. 63, No. 8, 01.01.2014, p. 2714-2726.

Research output: Contribution to journalArticle

Molina, Judith ; Rodriguez Diaz, Rayner ; Fachado, Alberto ; Jacques-Silva, M. Caroline ; Berggren, Per Olof ; Caicedo-Vierkant, Diego A. / Control of insulin secretion by cholinergic signaling in the human pancreatic islet. In: Diabetes. 2014 ; Vol. 63, No. 8. pp. 2714-2726.
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