Cell Swelling-induced Insulin Secretion from INS-1E Cells is Inhibited by Extracellular Ca2+ and is Tetanus Toxin Resistant

Cell swelling-induced insulin secretion represents an alternative pathway of stimulation of insulin secretion. INS-1E rat tumor beta cells do not release insulin in response to cell swelling in presence of Ca2+ despite a good response to glucose challenge and appropriate increase in cell volume. Surprisingly, perifusion with Ca2+-depleted medium showed distinct secretory response of INS-1E cells to hypotonicity. Objective of this study was further characterization of the role of Ca2+ in secretory process in INS-1 and INS-1E cell lines. Ca2+ depleted hypotonic medium with 10 mu M BAPTA/AM (intracellular chelator) induced insulin secretion from both types of cells. We demonstrated expression of L-type Ca2+ channel Ca(V)1.2 and non-L-type Ca2+ channels Ca(V)2.1 (P/Qtype), Ca(V)2.2 (N-type), and Ca(V)3.1 (T-type) in both cell lines. Inhibition of L type channel with nifedipine and/or P/Q type with.-agatoxin IVA enabled distinct response to hypotonic medium also in INS-1E cells. Tetanus toxin (TeTx) in medium containing Ca2+ and a group of calcium channel blockers inhibited hypotonicity-induced insulin secretion from INS-1 cells but not from INS-1E cells. Conclusion: Hypotonicityinduced insulin secretion from INS-1E cells is inhibited by extracellular Ca2+, does not require intracellular Ca2+ and is TeTx resistant. Copyright (C) 2010 S. Karger AG, Basel