Original Publication Date
The Biophysical Journal
DOI of Original Publication
Date of Submission
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.
From The Biophysical Journal, Fendler, B., Zhang, M., Satin, L., et al., Synchronization of Pancreatic Islet Oscillations by Intrapancreatic Ganglia: A Modeling Study, Vol. 97, Page 722. Copyright © 2009 Biophysical Society. Published by Elsevier Inc. Reprinted with permission.
Is Part Of
VCU Pharmacology and Toxicology Publications