Amplitude Modulation of Pulsatile Insulin Secretion by Intrapancreatic Ganglion Neurons

  1. Lei Sha,
  2. Johanna Westerlund,
  3. Joseph H. Szurszewski and
  4. Peter Bergsten
  1. From the Department of Medical Cell Biology (J.W., P.B.), Uppsala University, Uppsala, Sweden; and the Department of Physiology and Biophysics (L.S., J.H.S.), Mayo Clinic and Mayo Foundation, Rochester, Minnesota.
  1. Address correspondence and reprint requests to Dr. Peter Bergsten, Department of Medical Cell Biology, Uppsala University, Box 571, SE-751 23 Uppsala, Sweden. E-mail: peter.bergsten{at}medcellbiol.uu.se .

Abstract

Neuron activity and insulin release were measured simultaneously from 33 preparations of intrapancreatic canine ganglia and pancreatic parenchyma adjacent to the ganglia. The electrical activity of single neurons of the ganglia was recorded with intracellular microelectrodes, and insulin release from the attached islets was determined with an enzyme-linked immunosorbent assay. 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 measurements of neuronal electrical activity showed a stable membrane potential of -53.5 ± 0.6 mV. Short, high-frequency (20 Hz) preganglionic nerve stimulation evoked action potentials and, in 46% of the preparations, a threefold rise in the insulin secretory rate associated with increased amplitude of the insulin pulses. The effects were blocked by 10 μmol/l tetrodotoxin (TTX). In other preparations, continuous low-frequency (0.05-0.5 Hz) preganglionic nerve stimulation evoked action potentials and, in 50% of the preparations, a gradual increase of insulin release associated with augmentation of insulin pulse amplitude without alteration of the duration. The effects were blocked by 50 μmol/l hexamethonium (HEX). In the remaining preparations, no change in insulin release was observed during nerve stimulation. In the absence of stimulation, neither TTX nor HEX affected the membrane potential or insulin secretion. These first simultaneous measurements of intrapancreatic ganglion activity and insulin secretion are consistent with amplitude modulation of pulsatile insulin secretion induced by changes in electrical activity in a population of intrapancreatic ganglion neurons.

Footnotes

  • [Ca2+]i, cytoplasmic calcium concentration; ELISA, enzyme-linked immunosorbent assay; ESPS, excitatory postsynaptic potential; HEX, hexamethonium; TTX, tetrodotoxin.

    • Accepted September 14, 2000.
    • Received June 7, 1999.
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