title: Ca2+ influx does not trigger glucose-induced traffic of the insulin granules and alteration of their distribution.
abstract: This study investigated mechanisms by which glucose increases readily releasable secretory granules via acting on preexocytotic steps, i.e., intracellular granule movement and granule access to the plasma membrane using a pancreatic beta-cell line, MIN6. Glucose-induced activation of the movement occurred at a substimulatory concentration with regard to insulin output. Glucose activation of the movement was inhibited by pretreatment with thapsigargin plus acetylcholine to suppress intracellular Ca2+ mobilization. Inhibitors of calmodulin and myosin light chain kinase also suppressed glucose activation of the movement. Simultaneous addition of glucose with Ca2+ channel blockers or the ATP-sensitive K+ channel opener diazoxide failed to suppress the traffic activation, and addition of these substances on top of glucose stimulation resulted in a further increase. Although stimulatory glucose had minimal changes in the intracellular granule distribution, inhibition of Ca2+ influx revealed increases by glucose of the granules in the cell periphery. In contrast, high K+ depolarization decreased the peripheral granules. Glucose-induced granule margination was abolished when the protein kinase C activity was downregulated. These findings indicate that preexocytotic control of insulin release is regulated by distinct mechanisms from Ca2+ influx, which triggers insulin exocytosis. The nature of the regulation by glucose may explain a part of potentiating effects of the hexose independent of the closure of the ATP-sensitive K+ channel.
authors: Department of Pharmacology, Oita University, Faculty of Medicine, Oita 879-5593, Japan. niki@med.iota-u.ac.jp
authors: Ichiro
authors: I
authors: Niki
authors: Tae
authors: T
authors: Niwa
authors: Wei
authors: W
authors: Yu
authors: Dorota
authors: D
authors: Budzko
authors: Takashi
authors: T
authors: Miki
authors: Takao
authors: T
authors: Senda
mesh_terms: D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D003981:Diazoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005947:Glucose / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D009568:Nitrendipine / Q000494:pharmacology; D010766:Phosphorylation; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
chemical_list: D007328:Insulin; D018994:Myosin Light Chains; D009568:Nitrendipine; D009543:Nifedipine; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate; D003981:Diazoxide; D002118:Calcium