Amplitude modulation of pulsatile insulin secretion by intrapancreatic ganglion neurons

Neuron activity and insulin release were measured simultaneously from 33 pr eparations of intrapancreatic canine ganglia and pancreatic parenchyma adja cent to the ganglia. The electrical activity of single neurons of the gangl ia was recorded with intracellular microelectrodes, and insulin release fro m the attached islets was determined with an enzyme-linked immunosorbent as say. Insulin release was 62 +/- 18 fmol preparation/min in the presence of 10 mmol/l glucose and pulsatile (3.7 +/- 0.4 min/pulse). Corresponding meas urements of neuronal electrical activity showed a stable membrane potential of -53.5 +/- 0.6 mV. Short, high-frequency (20 Hz) preganglionic nerve sti mulation evoked action potentials and, in 46% of the preparations, a threef old rise in the insulin secretory rate associated with increased amplitude of the insulin pulses. The effects were blocked by 10 mu mol/l tetrodotoxin (TTX). In other preparations, continuous low-frequency (0.05-0.5 Hz) prega nglionic nerve stimulation evoked action potentials and, in 50% of the prep arations, a gradual increase of insulin release associated with augmentatio n of insulin pulse amplitude without alteration of the duration. The effect s were blocked by 50 mu mol/l hexamethonium (HEX). In the remaining prepara tions, no change in insulin release was observed during nerve stimulation. In the absence of stimulation, neither TTX nor HEX affected the membrane po tential or insulin secretion. These first simultaneous measurements of intr apancreatic ganglion activity and insulin secretion are consistent with amp litude modulation of pulsatile insulin secretion induced by changes in elec trical activity in a population of intrapancreatic ganglion neurons.