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

Abstract

SummaryInsulin 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, --~ 10-11 mol/1). 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/1, respectively. Thus, the exocrine pancreas is indeed exposed to locally high concentrations of islet hormones. [Diabetologia (1995) 38: 262-268]

Hypoxia Inducible Factor-1 Mediates Effects of Insulin on Pancreatic Cancer Cells and Disturbs Host Energy Homeostasis

“…4 At high concentrations, interstitial insulin nourishes exocrine pancreatic cells. 5,6 When pancreatic cancer occurs, insulin may stimulate the growth of the cancer cells as well. In vitro, insulin has been found to stimulate proliferation and glycolysis in pancreatic cancer cells.…”

Intermediate Filament Keratins in The Exocrine Pancreas

“…Two estimates indicate that the concentration of insulin and somatostatin is in the nanomolar range. The first comes from a study evaluating saturable binding of iodinated tracer for insulin and somatostatin in the rat pancreas perfused anterograde or retrograde (219). Binding was higher for retrograde perfusion which was attributed to endogenous hormone released during anterograde perfusion.…”

“…These investigators concluded that the inhibitory effect of insulin antisera was mediated by the local release of and action on the exocrine pancreas of somatostatin and PP (165). In a related study, Nakagawa et al concluded that the net effect of islet peptides on the exocrine pancreas was negative because exocrine secretion was greater with retrograde than anterograde perfusion (219). Thus the action of insulin could be mediated at least in part by suppressing the secretion of inhibitory islet peptides.…”

“…This could be achieved using the hyperinsulinemic euglycemic clamp with automated insulin minipumps combined with continuous closed loop subcutaneous glucose monitoring devices (170). It could be argued that there is a greater requirement for high dose insulin because pancreatic acinar cells receive a portal blood flow (175) with ~10 times higher insulin concentration than the systemic circulation (218,219). Furthermore, stress hormones, such as adrenaline, cortisol and glucagon, and inflammatory cytokines (TNFα and IL-1β) reduce tissue sensitivity of insulin, so a higher dose of insulin may be necessary to overcome this.…”

Bradykinin-induced secretion of insulin, glucagon and somatostatin

“…In addition, islet hormone (insulin and somatostatin) receptors exist on the plasma membrane of pancreatic acinar cells and the periacinal islet hormone concentrations are at least 20-fold higher in concentration than those in the systemic circulation . Thus, pancreatic islet hormones may regulate the secretion of the exocrine pancreas (Nakagawa et al, 1995;Hasegawa et al, 1993).…”