title: Synergistic insulin release induced by glucose and carbachol is not associated with an increase in cytoplasmic free calcium levels.
abstract: Synergistic insulin release is observed in combination with muscarinic agonist and glucose. In order to define the role of changes in the cytoplasmic free Ca2+ level ([Ca2+]i), the effect of combination with carbachol and glucose on both phosphoinositide breakdown in rat pancreatic islets and [Ca2+]i dynamics in single fura 2-loaded B-cells was investigated. When the islets were prelabeled with myo-[2-3H]inositol, phosphoinositide breakdown was obtained and inositol trisphosphate levels were increased in the presence of carbachol (0.5 mM). Inositol trisphosphate levels induced by carbachol were further increased by co-stimulation with 16.7 mM glucose. [Ca2+]i in single-B-cells was increased by 16.7 mM glucose. A prompt, transient rise in [Ca2+]i was induced by carbachol. However, carbachol failed to augment the [Ca2+]i response in the presence of 16.7 mM glucose. These data suggest that a synergistic release of insulin occurs without an amplification of [Ca2+]i regardless of an increase in inositol trisphosphate.
authors.affiliation: Department of Surgery, Shimane Medical University, Izumo, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Kashiwada
authors.forename: K
authors.initials: K
authors.lastname: Tanigawa
authors.forename: Y
authors.initials: Y
authors.lastname: Kato
authors.forename: K
authors.initials: K
authors.lastname: Tamura
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004357:Drug Synergism; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007328:Insulin; D010716:Phosphatidylinositols; D002217:Carbachol; D005947:Glucose; D002118:Calcium