Synchronization of pancreatic islet oscillations by intrapancreatic ganglia: a modeling study

Biophys J. 2009 Aug 5;97(3):722-9. doi: 10.1016/j.bpj.2009.05.016.

Abstract

Plasma insulin measurements from mice, rats, dogs, and humans indicate that insulin levels are oscillatory, reflecting pulsatile insulin secretion from individual islets. An unanswered question, however, is how the activity of a population of islets is coordinated to yield coherent oscillations in plasma insulin. Here, using mathematical modeling, we investigate the feasibility of a potential islet synchronization mechanism, cholinergic signaling. This hypothesis is based on well-established experimental evidence demonstrating intrapancreatic parasympathetic (cholinergic) ganglia and recent in vitro evidence that a brief application of a muscarinic agonist can transiently synchronize islets. We demonstrate using mathematical modeling that periodic pulses of acetylcholine released from cholinergic neurons is indeed able to coordinate the activity of a population of simulated islets, even if only a fraction of these are innervated. The role of islet-to-islet heterogeneity is also considered. The results suggest that the existence of cholinergic input to the pancreas may serve as a regulator of endogenous insulin pulsatility in vivo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetylcholine / metabolism*
  • Adenosine Triphosphate / metabolism
  • Algorithms
  • Animals
  • Calcium / metabolism
  • Carbachol / pharmacology
  • Cell Membrane / physiology
  • Computer Simulation
  • Cytosol / metabolism
  • Ganglia, Parasympathetic / drug effects
  • Ganglia, Parasympathetic / physiology*
  • Glucose / metabolism
  • Glycolysis / physiology
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / innervation
  • Islets of Langerhans / physiology*
  • Mice
  • Mitochondria / metabolism
  • Models, Neurological*
  • Muscarinic Agonists / pharmacology
  • Periodicity

Substances

  • Insulin
  • Muscarinic Agonists
  • Inositol 1,4,5-Trisphosphate
  • Adenosine Triphosphate
  • Carbachol
  • Glucose
  • Acetylcholine
  • Calcium