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 function via specific receptor binding. Theoretically peri-insular levels depend on the islet-acinar portal system, but the actual hormone levels have never been demonstrated. Rat pancreata were perfused anterogradely or retrogradely with 125I-insulin, -somatostatin, or -glucagon (each, approximately equal to 10(-11) mol/l). Tracer binding was determined from differences between influx and efflux radioactivity. Saturable binding was observed for insulin and somatostatin, but not for glucagon. Binding in the absence of unlabelled peptides was significantly higher during 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) and 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 unlabelled ligands competing with the tracers during anterograde perfusion. This conclusion was supported by the demonstration that endogenous insulin stimulation by D-glucose, but not by L-glucose, caused a decrease in labelled insulin binding only during anterograde perfusion. Displacement curves obtained during retrograde perfusion showed that interstitial concentrations of insulin and somatostatin were 7.5 x 10(-9) and 1.1 x 10(-9) mol/l, respectively. Thus, the exocrine pancreas is indeed exposed to locally high concentrations of islet hormones.
Nakagawa
A
A
Department of Medicine, University of Louisville, Kentucky, USA.
Stagner
J I
JI
Samols
E
E
D000818:Animals; D005934:Glucagon / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007515:Islets of Langerhans / Q000378:metabolism* / Q000502:physiology; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D010179:Pancreas / Q000378:metabolism* / Q000502:physiology; D010477:Perfusion; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism*
D007328:Insulin; D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D013004:Somatostatin; D005934:Glucagon