a mathematical model of the pancreatic duct cell generating.pdfVIP

ORIGINAL ARTICLE A Mathematical Model of the Pancreatic Duct Cell Generating High Bicarbonate Concentrations in Pancreatic Juice David C. Whitcomb, MD, PhD,* and G. Bard Ermentrout, PhD† he human pancreas secretes an impressive amount of so- Objective: To develop a simple, physiologically based mathemati- Tdium bicarbonate–rich fluid with each meal. The majority cal model of pancreatic duct cell secretion using experimentally de- of fluid and bicarbonate in pancreatic juice arises from the pan- rived parameters that generates pancreatic fluid bicarbonate concen- trations of 140 mM after CFTR activation. creatic duct cells even though they compose only about 5% of the pancreatic mass. Dysfunction of duct cell bicarbonate se- Methods: A new mathematical model was developed simulating a cretion, as seen with mutations with the cystic fibrosis trans- duct cell within a proximal pancreatic duct and included a sodium-2- membrane conductance regulator (CFTR) gene in cystic fibro- bicarbonate cotransporter (NBC) and sodium-potassium pump (NaK pump) on a chloride-impermeable basolateral membrane, CFTR on sis, leads to severe dysfunction of the pancreatic duct cells and the luminal membrane with 0.2 to 1 bicarbonate to chloride perme- eventual destruction of the exocrine pancreas.1–3 ability ratio. Chloride-bicarbonate antiporters (Cl−/HCO3− AP) were