title: Activation of alpha adrenergic and muscarinic receptors modifies early glucose suppression of cytoplasmic Ca(2+) in pancreatic β-cells.
abstract: Elevation of glucose induces transient inhibition of insulin release by lowering cytoplasmic Ca(2+) ([Ca(2+)]i) below baseline in pancreatic β-cells. The period of [Ca(2+)]i decrease (phase 0) coincides with increased glucagon release and is therefore the starting point for antisynchronous pulses of insulin and glucagon. We now examine if activation of adrenergic α2A and muscarinic M3 receptors affects the initial [Ca(2+)]i response to increase of glucose from 3 to 20mM in β-cells situated in mouse islets. In the absence of receptor stimulation the elevation of glucose lowered [Ca(2+)]i during 90-120 s followed by rise due to opening of voltage-dependent Ca(2+) channels. The period of [Ca(2+)]i decrease was prolonged by activation of the α2A adrenergic receptors (1 μM epinephrine or 100 nM clonidine) and shortened by stimulation of the muscarinic M3 receptors (0.1 μM acetylcholine). The latter effect was mimicked by the Na/K pump inhibitor ouabain (10-100 μM). The results indicate that prolonged initial decrease (phase 0) is followed by slow [Ca(2+)]i rise and shorter decrease followed by fast rise. It is concluded that the period of initial decrease of [Ca(2+)]i regulates the subsequent β-cell response to glucose.
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden. Electronic address: bo.hellman@mcb.uu.se.
authors.forename: Bo
authors.initials: B
authors.lastname: Hellman
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
authors.forename: Heléne
authors.initials: H
authors.lastname: Dansk
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Grapengiesser
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004837:Epinephrine / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010042:Ouabain / Q000378:metabolism; D043587:Receptor, Muscarinic M3 / Q000378:metabolism*; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*
chemical_list: D043587:Receptor, Muscarinic M3; D018341:Receptors, Adrenergic, alpha-2; D010042:Ouabain; D005947:Glucose; D000109:Acetylcholine; D002118:Calcium; D004837:Epinephrine
keywords: Acetylcholine; Cytoplasmic Ca(2+); Epinephrine; Glucose; Ouabain; β-cell