Different signaling pathways involved in glucose- and cell swelling-induced insulin secretion by rat pancreatic islets in vitro.

BACKGROUND

The objective was to compare signal transduction pathways exploited by glucose and cell swelling in stimulating insulin secretion.

METHODS

Isolated rat (Wistar) pancreatic islets were stimulated in vitro by 20 mmol/l glucose or 30% hypotonic medium (202 mOsm/kg) in various experimental conditions.

RESULTS

Glucose did not stimulate insulin release in calcium free medium. Cell swelling-induced insulin release in calcium free medium, even in the presence of the membrane permeable calcium chelator BAPTA/AM (10 micromol/l). Protein kinase C (PKC) inhibitor bisindolylmaleimide VIII (1 micromol/l) abolished the stimulation of insulin secretion by glucose but did not affect the swelling-induced insulin release. PKC activator phorbol 12-13-dibutyrate (1 micromol/l) stimulated insulin secretion in medium containing Ca2+ and did not potentiate insulin secretion stimulated by hypotonic extracellular fluid. Dilution of the medium (10-30%) had an additive effect on the glucose-induced insulin secretion. Noradrenaline (1 micromol/l) abolished glucose-induced insulin secretion but did not inhibit hypotonic stimulation either in presence or absence of Ca2+.

CONCLUSION

Glucose- and swelling-induce insulin secretion through separate signal transduction pathways. Hyposmotic stimulation is independent from both the extracellular and intracellular Ca2+, does not involve PKC activation, and could not be inhibited by noradrenaline. These data indicate a novel signaling pathway for stimulation of insulin secretion exploited by cell swelling.