IN-SITU BINDING OF ISLET HORMONES IN THE ISOLATED-PERFUSED RAT PANCREAS - EVIDENCE FOR LOCAL HIGH-CONCENTRATIONS OF ISLET HORMONES VIA THE ISLET-ACINAR AXIS

Insulin and somatostatin reportedly affect pancreatic acinar cell func tion via specific receptor binding. Theoretically peri-insular levels depend on the islet-acinar portal system, but the actual hormone level s have never been demonstrated. Rat pancreata were perfused anterograd ely or retrogradely with I-125-insulin, -somatostatin, or -glucagon (e ach, congruent to 10(-11) mol/l). Tracer binding was determined from d ifferences between influx and efflux radioactivity. Saturable binding was observed for insulin and somatostatin, but not for glucagon. Bindi ng in the absence of unlabelled peptides was significantly higher duri ng retrograde perfusion than during anterograde perfusion for insulin (25.9 +/- 2.6 vs 16.0 +/- 2.1%, mean +/- SD: each, n = 4; p < 0.001) a nd somatostatin (18.4 +/- 2.0 vs 13.6 +/- 1.2%; each, n = 3; p < 0.05) . Non-specific binding was similar in both directions. These findings are attributable to endogenous hormones acting as unlabeled ligands co mpeting with the tracers during anterograde perfusion. This conclusion was supported by the demonstration that endogenous insulin stimulatio n by D-glucose, but not by L-glucose, caused a decrease in labelled in sulin binding only during anterograde perfusion. Displacement curves o btained during retrograde perfusion showed that interstitial concentra tions of insulin and somatostatin were 7.5 x 10(-9) and 1.1 x 10(-9) m ol/l, respectively. Thus, the exocrine pancreas is indeed exposed to l ocally high concentrations of islet hormones.