Acute necrotizing pancreatitis in the opossum: Earliest morphological changes involve acinar cells

Disruption of IFT results in both exocrine and endocrine abnormalities in the pancreas of Tg737 mutant mice

“…The formation of halo-granules has been reported in acini shortly after secretin hyperstimulation as well as in models of pancreatitis induced by duct ligation. 70,71 These data suggest that the acini in the Tg737 orpk mutants are active in the release of granule contents and is in agreement with the high levels of amylase detected in the circulation at this time point. In addition, there were cytoplasmic vacuoles detected in the mutant acini that are not present in the controls (Figure 6b) suggestive of cell injury.…”

“…Halo-granules and elevated serum amylase have been reported previously in models of induced pancreatitis resulting from ductal obstruction or after hyperstimulation of the pancreas by secretin administration. 70,71 The formation of these halogranules has been attributed to fluid uptake by acinar cells and due to active granule secretion. Whether this pathology in the Tg737 orpk mutants represents a defect in regulating zymogen granule release or is simply an indicator of severe acinar cell injury remains to be determined; however, unlike the models of pancreatitis, there is no sign of a significant inflammatory response in the Tg737 orpk mutants.…”

“…In 5-day-old mutants, the acinar cells exhibited even more extensive vacuolization, reduction in the general size of the zymogen granules, and dilatation of the rough endoplasmic reticulum (Figure 6c, d). [70][71][72][73] In contrast to the acini, ultrastructural analysis of a-and b-cells in the islets showed no obvious morphological differences between wild-type and mutant pancreata at days 1 and 5 ( Figure 6e and data not shown).…”

Tauroursodeoxycholic acid reduces endoplasmic reticulum stress, trypsin activation, and acinar cell apoptosis while increasing secretion in rat pancreatic acini

“…This includes dilatation or vacuolation of the ER and loss of membrane-bound ribosomes (1,17,25,27). ER changes seem a common reaction of acini to the induction of ER stress (18,23).…”

Early events in acute pancreatitis

“…Another hypothesis suggested that periductal cells represented the site of initial damage and that pancreatic juice leaking from the pancreatic duct was responsible for the onset of pancreatitis [16]. Subsequent controlled studies performed in animal models that simulate the human disease have demonstrated that the acinar cell is the initial site of morphological damage [17]. This conclusion has been supported by genetic studies in patients with a hereditary form of pancreatitis that is linked to mutations in the trypsinogen gene [18,19].…”