Immunofluorescence and Electron-Microscopic Observations of Intermediate Cells in the Pancreas of Mice, Rats and Humans

Abstract

The immunohistochemical method supplemented with a transmission electron-microscopic survey was used to investigate the pancreas of mice, rats and humans to demonstrate intermediate cells. Indirect immunofluorescence was applied to paraffin sections of pancreatic samples of normal rats and autopsied humans to localize amylase in the islets and excretory duct cells. The amylase immunofluorescent spots were occasionally detected in the apices and perinuclear cytoplasm of few islet and excretory duct cells, which completely disappeared in the specificity control sections. These cells, respectively, represented the islet amylase and duct amylase intermediate cells. The ultrastructural survey was conducted on pancreatic tissue samples from normal and streptozotocin-diabetic mice and rats to prove the existence of these intermediate cells. Three morphologically distinct types of intermediate cells were recognized and characterized into β-acinar, α-acinar and duct acinar types. The β-acinar and α-acinar cells contained numerous secretory granules with few large and dense, membrane-bound zymogen granules. No clear difference in the frequency of these cells between normal and diabetic tissues was qualitatively observed in either mice or rats. The duct acinar cells were occasionally seen in few small intercalated ducts of the normal mouse pancreas, which contained few dense, membrane-bound zymogen granules adjacent to a prominent Golgi complex. On the other hand, no δ-acinar, pancreatic polypeptide (PP)-acinar or acinoislet cells were observed in both normal and diabetic animals. In conclusion, the present study provides immunohistochemical and morphological evidence on the existence of different types of intermediate cells in the normal and streptozotocin-diabetic pancreas of mice, rats and humans. Although no prevalence of these cells in the streptozotocin-diabetic pancreas was observed qualitatively, their existence throws light on the possible transformation between structurally and functionally different pancreatic cells when subjected to pathological trauma. This concept might be of great significance in β-cell regeneration in insulin-dependent diabetes mellitus.

β-Cell regeneration: the pancreatic intrinsic faculty

“…cells expressing multiple markers) suggests that exocrine cells can transdifferentiate directly into b-cells -ductal cells after 90% PX [56], acinar cells after PDL [57], and acinar and ductal cells in human insulin promoter-Ifng mice in which g-interferon expression is driven from the insulin gene promoter [58] (Table 1). The coexpression of insulin and amylase has led to the hypothesis that acinar cells could represent progenitors to b-cells during regeneration in these different models [57,[59][60][61][62]. In fact, two studies using genetic lineage-tracing approaches have so far demonstrated direct reprogramming of adult acinar cells, either to b-cells or to adipocytes, by ectopic b-cell-specific transcription factor expression or after inactivation of Myc, respectively [63,64].…”

Diabetogenic effects of streptozotocin on endocrine pancreatic islets, adrenal and carbohydrate profiles in turtles,Lissemys punctata punctata(Bonnoterre) (Reptilia: Chelonia)

“…There are reports that exocrine cells are frequently transformed into endocrine cells, which are produced probably from the newly formed islets in the small pancreatic ducts after streptozotocin treatment in transgenic mice (Gu et al 1997). Morphologically, distinct intermediate beta-acinar, alpha-acinar and duct-acinar cells, have been reported to occur in streptozotocin-induced diabetic mice, hamsters and humans (Aughsteen 2002). Guz et al (2001) reported that new beta cells are formed with restoration of normoglycemia after one week of streptozotocin treatment in mice (Guz et al 2001).…”

Transgenic and other experimental models of pancreas and islet damage

“…Intriguingly, many different cell types in the pancreas are affected by the loss of β‐cells: some have reported the appearance of acinar cells expressing insulin and low levels of pdx1 [32–34]. Similarly, others have described the expression of insulin in exocrine pancreas cells (replicating ductal cells) in adult rats after a single diabetogenic dose of alloxan [35].…”