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

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

Diabetes (2014-03-25)
Judith Molina, Rayner Rodriguez-Diaz, Alberto Fachado, M Caroline Jacques-Silva, Per-Olof Berggren, Alejandro Caicedo
ABSTRACT

Acetylcholine regulates hormone secretion from the pancreatic islet and is thus crucial for glucose homeostasis. 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 acetylcholine not only stimulates the insulin-secreting β-cell via the muscarinic acetylcholine receptors M3 and M5, but also the somatostatin-secreting δ-cell via M1 receptors. Because somatostatin is a strong inhibitor of insulin secretion, we hypothesized that cholinergic input to the δ-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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-CHRM1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-CHRM3 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-Somatostatin Antibody, clone YC7, culture supernatant, clone YC7, Chemicon®
Sigma-Aldrich
Anti-Muscarinic Acetylcholine Receptor m1 Antibody, Chemicon®, from rabbit