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 language | English |
|---|---|
| Pages (from-to) | 2714-2726 |
| Number of pages | 13 |
| Journal | Diabetes |
| Volume | 63 |
| Issue number | 8 |
| DOIs | |
| State | Published - Jan 1 2014 |
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ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
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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 journal › Article
}
TY - JOUR
T1 - Control of insulin secretion by cholinergic signaling in the human pancreatic islet
AU - Molina, Judith
AU - Rodriguez Diaz, Rayner
AU - Fachado, Alberto
AU - Jacques-Silva, M. Caroline
AU - Berggren, Per Olof
AU - Caicedo-Vierkant, Diego A
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84905040917&partnerID=8YFLogxK
U2 - 10.2337/db13-1371
DO - 10.2337/db13-1371
M3 - Article
C2 - 24658304
AN - SCOPUS:84905040917
VL - 63
SP - 2714
EP - 2726
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 8
ER -