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The nervous system has a significant impact in glucose homeostasis and endocrine pancreatic secretion in humans, especially during the cephalic phase of insulin release (CPIR); that is, before a meal is absorbed. However, the underlying mechanisms of this neural-pancreatic interaction are not well understood and therefore often neglected, despite their significance to achieving an optimal glucose control. As a result, the dynamics of insulin release from the pancreas are currently described by mathematical models that reproduce the behavior of the β cells using exclusively glucose levels and other hormones as inputs. To bridge this gap, we have combined, for the first time, metabolic and neural mathematical models in a unified system to reproduce to a great extent the ideal glucoregulation observed in healthy subjects. Our results satisfactorily replicate the CPIR and its impact during the post-absorptive phase. Furthermore, the proposed model gives insight into the physiological interaction between the brain and the pancreas in healthy people and suggests the potential of considering the neural information for restoring glucose control in people with diabetes. Graphical Abstract (a) Physiological scenario. Diagram of the biological interaction among the most important organs involved in glucose control during meal intake. (b) Scheme of the unified bio-inspired neural-metabolic model. Each of the boxes represents one subsystem of the model. The pink shades boxes depicts the novel subsystems introduced to the current metabolic models (grey shaded boxes). Insulin-related action and mass fluxes (solid black lines) and glucose-related action and mass flux (dotted black lines) are depicted to show the relationship among the blocks. I(t), I c (t), G(t) and SI related to plasma insulin, plasma cephalic insulin, plasma glucose and insulin sensitivity, respectively.

Modeling the effect of the cephalic phase of insulin secretion on glucose metabolism