title: Control of insulin secretion by cholinergic signaling in the human pancreatic islet.
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.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL.
authors.forename: Judith
authors.initials: J
authors.lastname: Molina
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, FLDiabetes Research Institute, University of Miami Miller School of Medicine, Miami, FLThe Rolf Luft Research Center for Diabetes & Endocrinology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Rayner
authors.initials: R
authors.lastname: Rodriguez-Diaz
authors.affiliation: Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL.
authors.forename: Alberto
authors.initials: A
authors.lastname: Fachado
authors.affiliation: Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL.
authors.forename: M Caroline
authors.initials: MC
authors.lastname: Jacques-Silva
authors.affiliation: Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FLThe Rolf Luft Research Center for Diabetes & Endocrinology, Karolinska Institutet, Stockholm, SwedenDivision of Integrative Biosciences and Biotechnology, WCU Program, University of Science and Technology, Pohang, Korea per-olof.berggren@ki.se acaicedo@med.miami.edu.
authors.forename: Per-Olof
authors.initials: PO
authors.lastname: Berggren
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, FLDiabetes Research Institute, University of Miami Miller School of Medicine, Miami, FLDepartment of Physiology and Biophysics, Miller School of Medicine, University of Miami, Miami, FLProgram in Neuroscience, Miller School of Medicine, University of Miami, Miami, FL per-olof.berggren@ki.se acaicedo@med.miami.edu.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Caicedo
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D015374:Biosensing Techniques; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D003593:Cytoplasm; D005786:Gene Expression Regulation; D005934:Glucagon / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013004:Somatostatin / Q000378:metabolism
chemical_list: D007328:Insulin; D011976:Receptors, Muscarinic; D013004:Somatostatin; D005934:Glucagon; D000109:Acetylcholine; D002118:Calcium