Stimulation of insulin release by elevated pressure gradient.

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In an attempt to stimulate the contractile events which presumably lead to intracellular translocation and exocytosis of the beta granule, the effect of elevated pressure on the rate of insulin release was studied. In vitro preparations of pancreas were incubated in media of low glucose content (1.65 mM) for several consecutive 15 min periods. The effect of pressure gradients, ranging from 0 to 45 mm Hg above atmospheric pressure, on insulin release was tested during the second period by introducing a mixture of 95% O2-5% CO2 into the incubation flasks. The results have shown that: 1) a rise in the pressure gradient over the gas phase was accompanied by an increase in the concentration of insulin released into the medium; 2) there was a direct relationship between the pressure gradient and the rate of insulin release; 3) the enhanced rate of insulin release caused by elevated pressure was not reversed immediately after release of pressure, but the effect was completely abolished within a period of 15 min; and 4) the stimulating effect of high glucose concentration on the rate of insulin release was completely blocked in the presence of 1 mM DNP, but the pressure-induced stimulation of insulin release was insensitive to this agent. In view of recent evidence implicating the microtubular-microfilamentous system in the secretory process of insulin, it is suggested that the application of pressure to the islet cells provides the necessary motive force to facilitate the intracellular translocation and extrusion of the beta granules normally performed by the beta cell contractile structures.