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

Abstract

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.

Diabetes is a Complex Neurological, Multisystemic, Multipathological and Polygenomic Disorder: the Use of Strannik Software as an Effective Modality to Illustrate Its Complexity

“…the role of the amygdala (receives and processes sensory data), hypothalamus (generates neuroendocrine output/hormones), brain stem, hippocampus (shortterm memory) [128], cerebral cortex (long-term memory) [129], and the transmitting mechanism -the vagus nerve; which are implicated in this enormously sophisticated process; and hence which play an immensely significant role in the regulation of blood glucose levels by the coherent and biodynamic function of the brain with the pancreas, endocrines, etc. [130][131][132][133].…”

The sweet taste receptor, glucose transporters, and the ATP-sensitive K+ (KATP) channel: sugar sensing for the regulation of energy homeostasis

“…Glucose and metabolic sensors for cephalic-phase insulin release (CPIR) Oral stimulation with food elicits CPIR prior to nutrient absorption, which lasts for 3-6 min and limits hyperglycemia for hours after the meal to maintain glucose homeostasis [24]. Neural pathways for CPIR initiate from food-related sensory inputs that activate parasympathetic neurons in the dorsal motor nucleus of the vagus.…”

Effects of Nutrient Intake during Pregnancy and Lactation on the Endocrine Pancreas of the Offspring

“…Part of the secretion of insulin is controlled by the central nervous system, which plays a major role in the cephalic phase of insulin release (i.e., first phase). This corresponds to the pre-absorptive secretion of insulin in response to neural signals triggered by meal olfactory clues rather than changes in plasma glucose concentrations after meal intake [29,30]. Between the two components of the autonomic nervous system, the PNS is the one that carries out a significant role in regulating insulin secretion.…”

“…Between the two components of the autonomic nervous system, the PNS is the one that carries out a significant role in regulating insulin secretion. This mainly involves the release of acetylcholine and activation of muscarinic receptor 3 located on the beta cells [11,30]. However, non-cholinergic mechanisms mediated by neuropeptides such as VIP and GRP have also been reported in human and pigs.…”