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

Morten Gram Pedersen ^*, Richard Bertram  and Arthur Sherman 

^* Department of Mathematics, Technical University of Denmark, Kgs. Lyngby, Denmark; Department of Mathematics and Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida; and Laboratory of Biological Modeling, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland

Correspondence: Address reprint requests to Arthur Sherman, Tel.: 301-496-4325; E-mail: asherman{at}nih.gov.

Insulin secretion from pancreatic ß-cells is pulsatile with a period of 5–10 min 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 ß-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.

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