1994 Volume 41 Issue 6 Pages 677-683
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.