The Pancreatic Exocrine Cell

Although it is possible to list all of the mammalian secretory cells and to note in some detail the biochemical nature of both precursor material and final secretory product, as well as to describe the intracellular pathway of secretory product formation, this would defeat the purpose of the current discourse. Rather, it will be more instructive to examine one secretory cell in detail and to compare it to several other representative cell types. From this analysis, one may derive an overview of the general mechanisms of secretion. For this purpose, I have chosen as a starting point the pancreatic exocrine cell because this cell has been one of the most thoroughly investigated, and its secretory pattern provides an ideal model on which to build broad concepts. 

The pancreatic acinar cells are serous cells forming tubuloacinar or tubuloalveolar glands in the body of the pancreas. The acinus is composed of a single layer of pyramidal cells, with the broad bases of the 

Our current knowledge of the intracellular sequence of events regarding the formation of pancreatic zymogen granules is largely a result of the investigative efforts of Palade and his co-workers. In a classic electron microscopic radioautographic study, Caro and Palade (1964) followed the uptake and intracellular distribution of a pulse label of tritiated leucine. The label was administered intravenously to rats sub- 

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Figure 11. Schematic of the intracellular transport pathway of enzymes and precursors in the pancreatic exocrine cell (based on the data presented...

Caro, L. G., and Palade, G. E., 1964, Protein synthesis, storage, and discharge in the pancreatic exocrine cell. An autoradiographic study, /. Cell Biol. 20 473. 

Genetic mannosidosis has been described in man, Angus cattle and Murray Gray cattle, and is characterized by a deficiency of a-mannosidase leading to storage of excess mannose-rich oligosaccharides in lysosomes. Pathologically, there is vacuolation of reticuloendothelial cells in the liver and lymph nodes, pancreatic exocrine cells, and neurons. Affected cattle are ataxic, uncoordinated, fail to thrive, and die in the first year of life. 

The trypsin family of proteases plays a role in acute and chronic pancreatitis, as well as leads to its ultimate destruction [4, 105]. In pancreatitis, active exocrine enzymes are prematurely released inside the pancreatic duct. Various factors can contribute to the development of acute pancreatitis. Trypsinogen, chymotrypsinogen, procarboxypeptidase, and proelastase are inactive proforms of proteolytic enzymes produced by the pancreatic acinar cells. Following secretion these enzymes are activated in a cascade that converts trypsinogen to trypsin in the duodenum and/or small intestine. 

Al Martini s serum levels of pancreatic amylase (which digests dietary starch) and pancreatic lipase were elevated, a finding consistent with a diagnosis of acute and possibly chronic pancreatitis. The elevated levels of these enzymes in the blood are the result of their escape from the inflamed exocrine cells of the pancreas into the surrounding pancreatic veins. The cause of this inflammatory pancreatic process in this case was related to the toxic effect of acute and chronic excessive alcohol ingestion. 

The relative amount of membrane (%) is presented for a hepatocyte and a pancreatic exocrine cell. ER = endoplasmic reticulum. Adapted from [122], p. 553. 

Figure 2. Diagrammatic representation of a pancreatic exocrine cell. Secretory precursor proteins are synthesized by the RER and sequestered in the cisternae of that organelle (1). The material is then transferred by way of small vesicles to mature Golgi saccules and vacuoles (2). Within the vacuoles the secretory precursors are concentrated with the removal of water (3) and the Golgi vacuole is transformed into a mature zymogen granule (4). In response to the appropriate stimulus, the membrane of the zymogen granule fuses with the apical plasma membrane (5), and the final secretory product is released to the lumen of the gland.

The pancreas is a gland in the abdomen lying in the curvature of the stomach as it empties into the duodenum. The pancreas functions primarily as an exocrine gland, although it also has endocrine function. The exocrine cells of the pancreas are called acinar cells. They produce an alkaline fluid known as pancreatic... 

Why this elaborate mechanism for getting active digestive enzymes into the gastrointestinal tract Synthesis of the enzymes as inactive precursors protects the exocrine cells from destructive proteolytic attack. The pancreas further protects itself against self-digestion by making a specific inhibitor, a protein called pancreatic trypsin inhibitor (p. 231), that effectively prevents... 

Inflammation of the pancreas, pancreatitis, can be a consequence of excessive alcohol intake and causes severe pain. In chronic pancreatitis the exocrine cells which produce enzymes are damaged and smaller quantities of enzyme are released into the gut so that a major portion of the diet remains undigested and is not absorbed. Patients suffer malnutrition and weight loss. 

The pancreas possesses both endocrine and exocrine fnnctions. The islets of Langerhans, which contain the cells of the endocrine pancreas, secrete insnlin, glncagon, somatostatin, and other polypeptide hormones. The exocrine pancreas is composed of acini that secrete about 1 to 2 L/day of isotonic fluid that contains water, electrolytes, and pancreatic enzymes necessary for digestion. Bicarbonate is secreted primarily by the centroacinar (ductular) cells, and is the principal ion of physiologic importance. Pancreatic juice is delivered to the duodenum via the pancreatic ducts (Fig. 39-1) where the alkaline secretion (pH about 8.3) neutralizes gastric acid and provides an appropriate pH for maintaining the activity of pancreatic enzymes."... 

Pancreas A major endocrine and exocrine organ located behind the stomach. It secretes pancreatic juice into the duodenum to neutrahze the effluent from the stomach and supply digestive enzymes. It also synthesizes and secretes the hormones insulin, glucagon, and somatostatin into the bloodstream from cells within the islets of Langerhans. 

Fig. 1. Exocrine pancreas from a rat treated with l-cyano-2-hydroxy-3-butene, a naturally occurring phyochemical that induces widespread pancreatic apoptosis within 12 h of a 200 mg/kg oral dose. Arrows point to pancreatic acinar cells with the typical apoptotic nuclear morphology (i.e., homogeneous chromatin crescents or caps with intact nuclear membrane). The arrowhead indicates an apoptotic body in which the nucleus is not in the plane of section. Hematoxylin and eosin, bar = 25 pm.

Swift, G.H., Liu, Y., Rose, S.D., Bischof, L.J., Steelman, S., Buchberg, A.M., Wright, C.V., MacDonald, R.J. 1998. An endocrine-exocrine switch in the activity of the pancreatic homeodomain protein PDX1 through formation of a trimeric complex with PBXlb and MRG1 (MEIS2). Mol. Cell Biol. 18, 5109-5120. 

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