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Primers on Molecular Pathways : Bicarbonate Transport by the Pancreas

The pancreas has both endocrine and exocrine functions. As an endocrine organ, stimulation of the pancreatic -cells results in insulin secretion to control systemic glucose levels. The exocrine function of the pancreas and the need for alkaline pancreatic secretion (pH 8.0–8.5) have been appreciated for more than 40 years. Yet, our knowledge of the cellular mechanisms (signaling, transporters and channels) which accomplish these critical functions has evolved greatly. In the mid-1990s, basolateral Na-bicarbonate (HCO3–) uptake by NBCe1 (Slc4a4) was shown to be critical for the generation of approximately 75% of stimulated HCO3– secretion. In the last 10 years, several new HCO3– transporters in the Slc26 family and their interaction with the cystic fibrosis transmembrane conductance regulator-chloride channel have elucidated the HCO3– exit step at the ductal lumen. Most recently, both IRBIT (inositol 1, 4, 5-trisphosphate receptor-binding protein) and WNK [with no lysine (K)] kinase have been implicated as additional HCO3– secretory controllers.

cystic fibrosis transmembrane conductance regulator; SLC26 family; pancreatic duct

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