title: Stimulus-secretion coupling of hypotonicity-induced insulin release in BRIN-BD11 cells.
abstract: The stimulus-secretion coupling for hypotonicity-induced insulin release was investigated in BRIN-BD11 cells. A 50 mM decrease in extracellular NaCl caused a twofold increase in insulin release. The release of insulin evoked by hypotonicity progressively decreased in an exponential manner. The response to extracellular hypotonicity displayed a threshold value close to 20 mOsmol/L and a maximal response at about 70 mOsmol/ L. Hypotonicity also caused a rapid increase in cell volume followed by a regulatory volume decrease (RVD), cell membrane depolarization with induction of spike activity, and a rise in cytosolic Ca2+ concentration. 5-Nitro-2-(3-phenylpropylamino)benzoate inhibited the secretory response to hypoosmolarity, failed to affect the early increase in cell volume but prevented the RVD, and suppressed the hypotonicity-induced plasma membrane depolarization. Insulin release provoked by hypotonicity was inhibited by verapamil, absence of Ca2+, thapsigargin, furosemide, tributyltin, and diazoxide. On the contrary, tolbutamide augmented modestly insulin release recorded in the hypoosmolar medium. Last, a rise in extracellular K+ concentration, while augmenting basal insulin output, failed to affect insulin release in the hypoosmolar medium. Thus, the insulin secretory response to hypotonicity apparently represents a Ca2+-dependent process triggered by the gating of volume-sensitive anion channels with subsequent depolarization and gating of voltage-sensitive Ca2+ channels.
authors.affiliation: Laboratorie of Cell and Molecular Physiology, Brussels Free University, Brussels, Belgium.
authors.forename: Renaud
authors.initials: R
authors.lastname: Beauwens
authors.forename: Len
authors.initials: L
authors.lastname: Best
authors.forename: Nicolas
authors.initials: N
authors.lastname: Markadieu
authors.forename: Raphael
authors.initials: R
authors.lastname: Crutzen
authors.forename: Karim
authors.initials: K
authors.lastname: Louchami
authors.forename: Peter
authors.initials: P
authors.lastname: Brown
authors.forename: Allen P
authors.initials: AP
authors.lastname: Yates
authors.forename: Willy J
authors.initials: WJ
authors.lastname: Malaisse
authors.forename: Abdullah
authors.initials: A
authors.lastname: Sener
mesh_terms: D000086:Acetazolamide; D020533:Angiogenesis Inhibitors; D000818:Animals; D027321:Anion Transport Proteins / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D048429:Cell Size; D003600:Cytosol / Q000378:metabolism; D004232:Diuretics; D005665:Furosemide; D005942:Gluconates / Q000378:metabolism; D007038:Hypotonic Solutions; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D009579:Nitrobenzoates; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D012965:Sodium Chloride / Q000378:metabolism*; D014220:Trialkyltin Compounds
chemical_list: D020533:Angiogenesis Inhibitors; D027321:Anion Transport Proteins; D004232:Diuretics; D005942:Gluconates; D007038:Hypotonic Solutions; D007328:Insulin; D009579:Nitrobenzoates; D015221:Potassium Channels; D014220:Trialkyltin Compounds; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D012965:Sodium Chloride; C011559:tributyltin; D005665:Furosemide; D000086:Acetazolamide; C030691:gluconic acid; D002118:Calcium