%0 Journal Article
%T A closed-loop negative feedback model for the pancreas: A new paradigm and pathway to a cure.
%A Dressel TD
%A Custer CM
%J Medicine (Baltimore)
%V 103
%N 28
%D 2024 Jul 12
%M 38996137
%F 1.817
%R 10.1097/MD.0000000000038802
%X <B>OBJECTIVE: </B>To develop a model that describes how the pancreas functions, how the rate of synthesis of digestive enzymes is regulated, and finally what puts the pancreas to rest between meals.<BR><B>METHODS: </B>We applied the principals of control theory to previously published canine data to develop a model for how the canine pancreas functions. Using this model, we then describe the steps needed to apply this model to the human pancreas.<BR><B>RESULTS: </B>This new closed-loop negative feedback model describes what regulates digestive enzyme synthesis. This model is based on basolateral exocytosis of butyrylcholinesterase (BCHE) into the interstitial space. It is this level of BCHE * BCHE activity that controls the rate of canine pancreas digestive enzyme synthesis, and in the absence of stimulation from the vagus nerve, puts the pancreas to rest between meals.<BR><B>CONCLUSIONS: </B>Finding secretagogue-specific inhibitory enzymes in the human pancreas that are analogous to BCHE in the canine, and blocking its associated receptors, may lead to a cure for human pancreatitis.