Heterogeneity of the Exocrine Pancreas

The exocrine pancreas is generally considered to be a homogeneous organ at the morphological and functional levels. Recent work, reviewed here, has provided multiple reasons to question this. Morphologically, differences have been found in cell size and digestive enzyme content in "peri-" vs. "teleinsular" acini by methods including acinar separation, enzyme assay, and both light and electron microscopic immunocytochemistry. Detection of several blood group antigens in human acinar tissue showed striking cellular heterogeneity in a mosaic pattern. Stimulation of pancreatic lobules by specific secretagogues and separation of individual zymogen granules with microfluorometric assay of enzyme content also confirmed heterogeneity at the lobular and organellar level. Functionally, evidence that nonparallel digestive enzyme secretion can be taken as direct support for acinar heterogeneity is reviewed, as is the work leading to direct demonstration of secretagogue-specific heterogeneous sequestration and storage of nascent digestive enzyme protein. A general overview of pancreatic acinar cell specificity is presented; the model incorporates temporal changes in secretion from eligible acini, with secretagogue specificity of whole acini containing specific preset mixtures of digestive enzymes.