Regulation of Pancreatic Exocrine Function by Manganese

Abstract

The pancreas is a heterogenous organ consisting of clusters of endocrine cells that are dispersed throughout the exocrine tissue. The endocrine cells secrete insulin, glucagon, somatostatin, and a variety of other peptides into the blood. The exocrine tissue consists of acinar cells that synthesize digestive enzymes and duct cells that produce bicarbonate rich fluid. Under normal physiological conditions numerous factors interact to enable the endocrine and exocrine pancreas to respond to a meal in a highly coordinated manner that contributes to the digestion and subsequent assimilation of ingested food. This regulation involves an interplay between neurotransmitters, nutrients, gastrointestinal hormones, and islet cell hormones acting through a variety of second messengers. Because of the relative richness of the pancreas in manganesel, it has been suggested that this divalent cation may also participate in the regulation of pancreatic function. This hypothesis is supported by several types of observations. Thus, manganese is taken up from the systemic circulation by the pancreas, and the concentration of manganese in the pancreatic duct is greater than in the blood2. Second-generation manganese-deficient animals may exhibit ultrastructural damage or complete atrophy of the pancreatic acinar ce113,4. These animals also exhibit beta cell dysfunction that is manifested by decreased insulin secretion and synthesis, and enhanced insulin degradations5.