Population-of-controllers model explains heterogeneous insulin secretion experiments

De Gaetano, Andrea, Gaz, Claudio Roberto, Palumbo, Pasquale and Panunzi, Simona (2014) Population-of-controllers model explains heterogeneous insulin secretion experiments. In: 9th European Conference on Mathematical and Theoretical Biology (ECMTB); 15-19 Jun 2014, Gothenburg, Sweden. (Unpublished)


The secretion of insulin by the pancreas has been the object of much attention over the past several decades. Insulin is known to be secreted by pancreatic beta-cells in response to hyperglycemia: its blood concentrations however exhibit both high-frequency (period approx. 5 minutes) and low-frequency (period approx. 1.5 hours) oscillations. Furthermore, characteristic insulin secretory responses to challenge maneuvers have been described, such as frequency entrainment upon sinusoidal glycemic stimulation, substantial insulin peaks following minimal glucose administrations, progressively strengthened insulin secretion response after repeated administrations of the same amount of glucose, insulin and glucose characteristic curves after Intra-venous administration of glucose boli in health, in pre-diabetic conditions and in Type 2 Diabetes Mellitus. Previous modeling of beta-cell physiology has been mainly directed to the intracellular chain of events giving rise to single-cell or cell-cluster hormone release oscillations, but the large size, long period and complex morphology of the diverse responses to whole-body glucose stimuli has not yet been coherently explained. Since the seminal work of Grodsky it was hypothesized that the population of pancreatic beta-cells, possibly functionally aggregated in Langerhan´s islets, could be viewed as a set of separate, similar but not identical controllers. The present work shows how a single model based on a population of independent islet controllers can reproduce very closely a diverse array of actually observed experimental results, with the same set of working parameters.

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