Influence of a constant or a modulated pressure on insulin secretion by intact murine islets of Langerhans: existence of a threshold effect.

Pressure effect on cultured islets was investigated to simulate the behavior of the endocrine pancreas when subjected to an anatomical change in its environment. Insulin secretion from islets seeded on glass was determined by radioimmunoassays after 12-h exposure to constant or sine-wave pressure perturbation, at 37 degrees C and pH 7.4, under well-defined conditions applied through the culture medium. A specially devised setup allowed control of the constant component Po, the amplitude A, and the frequency f of the pressure perturbation. Under constant conditions, three Po values (760, 760 + 110, 760 + 250 mm Hg) were explored. Under sine-wave conditions, two frequencies (f = 0.2 and 4.33 Hz) were investigated for Po = 760 + 110 mm Hg and A = 10 mm Hg, as well as three amplitude values (A = +/-10, +/-50, and +/-110 mm Hg) for Po = 760 mm Hg and f = 0.2 Hz. Constant pressure inhibits secretion, by a factor of up to 60%, as well as low frequency (also by approximately 60%). Low amplitudes enhance secretion (by 41 and 31%), whereas a higher amplitude has a marked inhibiting effect (by 70%). In all cases, no linearity was observed, showing the existence of a threshold pressure effect. These results suggest that pressure may be an important parameter in certain forms of endocrine pancreatic dysfunctions.