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Biophys. J. BioFAST: First Published April 15, 2005. doi:10.1529/biophysj.104.055681
© 2005 by the Biophysical Society.

A more recent version of this article appeared on July 1, 2005.
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BIOPHYSICAL THEORY AND MODELING

Intra- and Inter-islet Synchronization of Metabolically Driven Insulin Secretion

Morten Gram Pedersen 1, Richard Bertram 2 and Arthur Sherman 3*

1 Technical University of Denmark
2 Florida State University
3 National Institutes of Health

* To whom correspondence should be addressed. E-mail: asherman{at}nih.gov.

Submitted on November 8, 2004
Revised on December 7, 2004
Accepted on 6 April 2005


  Abstract
Insulin secretion from pancreatic {beta}-cells is pulsatile with a period of 5-10 minutes and is believed to be responsible for plasma insulin oscillations with similar frequency. To observe an overall oscillatory insulin profile it is necessary that the insulin secretion from individual {beta}-cells is synchronized within islets, and that the population of islets is also synchronized. We have recently developed a model in which pulsatile insulin secretion is produced as a result of calcium-driven electrical oscillations in combination with oscillations in glycolysis. We use this model to investigate possible mechanisms for intra-islet and inter-islet synchronization. We show that electrical coupling is sufficient to synchronize both electrical bursting activity and metabolic oscillations. We also demonstrate that islets can synchronize by mutually entraining each other by their effects on a simple model ``liver'', which responds to the level of insulin secretion by adjusting the blood glucose concentration in an appropriate way. Since all islets are exposed to the blood, the distributed islet-liver system can synchronize the individual islet insulin oscillations. Thus, we demonstrate how intra-islet and inter-islet synchronization of insulin oscillations may be achieved.

Key Words: Pulsatile insulin release, entrainment, glucose homeostasis, mathematical modeling




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Copyright © 2005 by the Biophysical Society.