Cold-induced insulin release in vitro: evidence for exocytosis

Exposure of isolated pancreatic islets (mouse or rat) to low temperature (2 degrees C) evoked a threefold increase in insulin release irrespective of the glucose concentration in the incobation medium. Cold-induced release was transient and rewarming to 37 degrees C restored the sensitivity of B-cells to gluocose stimulation. In islets cooled to 2 degrees C, exocytotic profiles could easily be detected both by thin-section and freeze-fracture electron microscopy. As revealed by the freeze-fracture technique, the number of exocytotic profiles per membrane area was increased three- to fourfold as compared to islet cells incubated at 20 degrees C. This was paralleled by intracellular fusion of secretory vesicles. Cold-induced insulin release was not affected by theophylline, cytochalasin B, omission of extracellular Ca++ or D600. Replacement of extracellular Na+ with choline or sucrose suppressed the increase in insulin release and in frequency of exocytotic profiles recorded after exposure to 2 degrees C. It is suggested that a redistribution of Ca++ from intracellular stores, possibly mediated by an increase in intracellular Na+ triggers exocytosis of insulin granules upon exposure to cold.