Stimulus-secretion coupling of hypotonicity-induced insulin release in BRIN-BD11 cells

• Published in: Endocrine 2006-12, Vol.30 (3), p.353-363
• Main Authors: Beauwens, Renaud, Best, Len, Markadieu, Nicolas, Crutzen, Raphael, Louchami, Karim, Brown, Peter, Yates, Allen P, Malaisse, Willy J, Sener, Abdullah
• Format: Article
• Language: English
• Subjects: Acetazolamide; Angiogenesis Inhibitors; Animals; Anion channels; Anion Transport Proteins - metabolism; Benzoic acid; Calcium - metabolism; Calcium channels; Calcium channels (voltage-gated); Cell Line; Cell membranes; Cell Size; Channel gating; Cytosol - metabolism; Depolarization; Diuretics; Endocrinology; Furosemide; Gluconates - metabolism; Hypotonic Solutions; Hypotonicity; Insulin; Insulin - metabolism; Insulin Secretion; Insulin-Secreting Cells - cytology; Insulin-Secreting Cells - metabolism; Membrane potential; Membrane Potentials - physiology; Nitrobenzoates; Potassium Channels - metabolism; Rats; Secretion; Sodium Chloride - metabolism; Stimulus-secretion coupling; Thapsigargin; Tolbutamide; Trialkyltin Compounds; Tributyltin; Verapamil
• ISSN: 1355-008X; 1559-0100
• DOI: 10.1007/s12020-006-0014-3

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.