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 be havior of the endocrine pancreas when subjected to an anatomical chang e in its environment. Insulin secretion from islets seeded on glass wa s determined by radioimmunoassays after 12-h exposure to constant or s ine-wave pressure perturbation, al 37 degrees C and pH 7.4, under well -defined conditions applied through the culture medium. A specially de vised setup allowed control of the constant component P-o, the amplitu de A, and the frequency f of the pressure perturbation. Under constant conditions, three P-o values (760, 760 + 110, 760 + 250 mm Hg) were e xplored. Under sine-wave conditions, two frequencies (f = 0.2 and 4.33 Hz) were investigated for P-o = 760 + 110 mm Hg and A = 10 mm Hg, as well as three amplitude values (A = +/-10, +/-50, and +/-110 mm Hg) fo r P-o = 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 similar to 60%). Low amplitudes enhance secretion (by 41 and 31%), whereas a h igher amplitude has a marked inhibiting effect (by 70%). In all cases, no linearity was observed, showing the existence of a threshold press ure effect. These results suggest that pressure may be an important pa rameter in certain forms of endocrine pancreatic dysfunctions.