Protein is key for digestive function of the pancreas

Scientists have identified a protein that is necessary for secretion of digestive enzymes by the pancreas. The research, published in the September issue of Developmental Cell, enhances the understanding of the normal physiology of the pancreas and provides some insight into abnormal processes that may lead to pancreatic disease.

While the most famous role of the pancreas is the production of hormones like insulin that regulate blood sugar, the pancreas also produces digestive enzymes that are secreted into the gastrointestinal tract and break down carbohydrates, proteins, and fats present in the foods we eat. The harsh digestive enzymes secreted by pancreatic acinar cells are packaged into units called zymogen granules. Upon stimulation with hormones like cholecystokinin (CCK), zymogen granules are emptied via a process called exocytosis into ducts leading to the small intestine. In some pathological conditions, the digestive enzymes are abnormally secreted backwards into the blood, damaging the pancreas and leading to a condition called pancreatitis.

The complex mechanisms involved in exocytosis are not entirely understood. Dr. Wanjin Hong and colleagues from the Institute of Molecular and Cell Biology in Singapore examined a protein called VAMP8 that has been implicated in the process of exocytosis and is present on zymogen granules. The researchers studied mice that were genetically designed to be missing VAMP8 and found that the mice had pronounced pancreatic defects. Pancreatic acinar cells lacking VAMP8 had many more zymogen granules than control acinar cells. In addition, CCK did not stimulate exocytosis in VAMP8-deficient acinar cells. "These results suggest that VAMP8 plays a definite role in regulated enzyme secretion in pancreatic acinar cells," writes Dr. Hong.

The researchers went on to examine whether VAMP8 may play a role in pancreatitis. They administered stimuli known to induce pancreatitis and measured levels of digestive enzymes in the blood in the pancreases of normal and VAMP8-deficient mice. Compared to normal mice, mice lacking VAMP8 had substantially reduced blood levels of digestive enzymes and demonstrated partial resistance to pancreatitis. This suggests that VAMP8 may be involved in the abnormal secretion of digestive enzymes associated with pancreatitis. Further research is needed to establish whether VAMP8 is directly linked to pancreatitis.

Cheng-Chun Wang, Chee Peng Ng, Lei Lu, Vadim Atlashkin, Wei Zhang, Li-Fong Seet, and Wanjin Hong: "A Role of VAMP8/Endobrevin in Regulated Exocytosis of Pancreatic Acinar Cells"

Publishing in Developmental Cell, Volume 7, Number 3, September 2004, pages 359-371.

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