title: Thiopental-induced insulin secretion via activation of IP3-sensitive calcium stores in rat pancreatic β-cells.
abstract: While glucose-stimulated insulin secretion depends on Ca(2+) influx through voltage-gated Ca(2+) channels in the cell membrane of the pancreatic β-cell, there is also ample evidence for an important role of intracellular Ca(2+) stores in insulin secretion, particularly in relation to drug stimuli. We report here that thiopental, a common anesthetic agent, triggers insulin secretion from the intact pancreas and primary cultured rat pancreatic β-cells. We investigated the underlying mechanisms by measurements of whole cell K(+) and Ca(2+) currents, membrane potential, cytoplasmic Ca(2+) concentration ([Ca(2+)](i)), and membrane capacitance. Thiopental-induced insulin secretion was first detected by enzyme-linked immunoassay, then further assessed by membrane capacitance measurement, which revealed kinetics distinct from glucose-induced insulin secretion. The thiopental-induced secretion was independent of cell membrane depolarization and closure of ATP-sensitive potassium (K(ATP)) channels. However, accompanied by the insulin secretion stimulated by thiopental, we recorded a significant intracellular [Ca(2+)] increase that was not from Ca(2+) influx across the cell membrane, but from intracellular Ca(2+) stores. The thiopental-induced [Ca(2+)](i) rise in β-cells was sensitive to thapsigargin, a blocker of the endoplasmic reticulum Ca(2+) pump, as well as to heparin (0.1 mg/ml) and 2-aminoethoxydiphenyl borate (2-APB; 100 μM), drugs that inhibit inositol 1,4,5-trisphosphate (IP(3)) binding to the IP(3) receptor, and to U-73122, a phospholipase C inhibitor, but insensitive to ryanodine. Thapsigargin also diminished thiopental-induced insulin secretion. Thus, we conclude that thiopental-induced insulin secretion is mediated by activation of the intracellular IP(3)-sensitive Ca(2+) store.
authors.affiliation: Shandong Univ. School of Medicine, Institute of Physiology, Jinan, Shandong, China.
authors.forename: Hai-Qiang
authors.initials: HQ
authors.lastname: Dou
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Xu
authors.forename: Jin-Peng
authors.initials: JP
authors.lastname: Sun
authors.forename: Shujiang
authors.initials: S
authors.lastname: Shang
authors.forename: Shu
authors.initials: S
authors.lastname: Guo
authors.forename: Liang-Hong
authors.initials: LH
authors.lastname: Zheng
authors.forename: Chao-Chao
authors.initials: CC
authors.lastname: Chen
authors.forename: Iain C
authors.initials: IC
authors.lastname: Bruce
authors.forename: Xiao
authors.initials: X
authors.lastname: Yu
authors.forename: Zhuan
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D018686:Anesthetics, Intravenous; D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D004963:Estrenes / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007328:Insulin / Q000032:analysis / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012433:Ryanodine / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D013874:Thiopental / Q000494:pharmacology*
chemical_list: D018686:Anesthetics, Intravenous; D001896:Boron Compounds; D004963:Estrenes; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007328:Insulin; D015221:Potassium Channels; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D012433:Ryanodine; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D006493:Heparin; C109986:2-aminoethoxydiphenyl borate; D005947:Glucose; D013874:Thiopental; D002118:Calcium