The endocrine pancreas in chronic pancreatitis

Klöppel, Günter; G, Bommer; Commandeur, G.; Heitz, Ph. U.

doi:10.1007/bf00427003

Cited by 127 publications

(19 citation statements)

References 27 publications

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“…ation with ductal complexes in pancreatic duct obstruction and pancreatitis in humans [7,8]. The formation of ductal complexes in the pancreas is at least partially caused by a transdifferentiation of acinar to duct cells [9] which illustrates the remarkable differentiation plasticity of acinar cells.…”

mentioning

confidence: 99%

Modulation of rat pancreatic acinoductal transdifferentiation and expression of PDX-1 in vitro

Rooman¹,

Heremans²,

Heimberg³

et al. 2000

Diabetologia

177

180

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Regeneration, or neogenesis, of beta cells in adult pancreas is an important research issue because it could find applications in the restoration of the normal beta-cell mass in diabetic patients. In vitro neogenesis might be a means of generating additional beta cells intended for transplantation, as the number of beta cells that can be isolated from organ donors is very limited. Neogenesis can be induced in vivo in several ways [1] but the identity of the beta-cell precursors is not clear. Several lines of evidence suggest that, in addition to duct cells, exocrine acinar cells could be able to transdifferentiate into beta cells [2]. In several experimental models and pathological conditions, islet neogenesis is accompanied by the transformation of the normal exocrine tissue into ductal complexes, a process called acinoductal metaplasia. This is seen in the model of pancreatic duct ligation [3], transforming growth factor-alpha transgenic mice [4,5] and interferon-gamma transgenic mice [6]. Islet neogenesis has also been observed in associ- Diabetologia (2000) Abstract Aims/hypothesis. In adult pancreatic regeneration models exocrine acini are found to transdifferentiate to duct-like complexes. This has also been associated with the formation of new endocrine islet cells. We aimed to establish an in vitro model in which this transdifferentiation process is characterised and can be modulated. Methods. Purified rat pancreatic acini were cultured in suspension. Differentiation was analysed by immunocytochemistry, electron microscopy, western blotting and RT-PCR.Results. During culture acinar cells directly transdifferentiated without dividing, the cells lost their acinar phenotype and started to express cytokeratins 20 and 7 and fetal liver kinase-1 (Flk-1) receptors for vascular endothelial growth factor. Expression of the acinar pancreatic exocrine transcription factor (PTF-1) remained and the pancreatic duodenal homeoboxcontaining transcription factor (PDX-1) was induced. When transdifferentiation was completed, the cells started to express protein gene product 9.5, a panneuroendocrine marker. By combining these features, the transdifferentiated cells show similar characteristics to precursor cells during active beta-cell neogenesis. We were able to modulate the differentiation state by addition of nicotinamide or sodium butyrate, agents which are known to stimulate endocrine differentiation in other models. Conclusion/interpretation. Here, we present an in vitro system in which the cellular differentiation of putative pancreatic endocrine precursor cells and their PDX-1 expression can be modulated, thereby providing a possible model for the study of beta-cell transdifferentiation. [Diabetologia (2000) Corresponding author: L. Bouwens, VUB-Department of Experimental Pathology, Laarbeeklaan 103, B-1090 Brussels, Belgium Abbreviations: BrdU, Bromodeoxyuridine; CK7, cytokeratin 7; CK20, cytokeratin 20; Flk-1, fetal liver kinase-1; PDX-1, pancreatic duodenal homeodomain containing transcription factor; PGP9.5, ...

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mentioning

confidence: 99%

Modulation of rat pancreatic acinoductal transdifferentiation and expression of PDX-1 in vitro

Rooman¹,

Heremans²,

Heimberg³

et al. 2000

Diabetologia

177

180

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“…Surprisingly, the number of PP cells in chronic pancreatitis was not found to be decreased but, on the contrary, hyperplasia of PP cells was reported (Kloppel et al, 1978). If this finding is confirmed in future studies, it has to be assumed that chronic pancreatitis affects either the responsiveness of PP cells to stimuli, possibly by damage to nerves, or the secretory function of the PP cells.…”

Section: Discussionmentioning

confidence: 78%

Basal and postprandial serum concentrations of pancreatic polypeptide in pancreatitis and after pancreaticoduodenectomy

Lamers¹,

Diemel²

1981

Postgraduate Medical Journal

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SummaryBasal and postprandial serum concentrations of pancreatic polypeptide (PP) were measured in 22 normal subjects, in 6 patients with a history of acute pancreatitis, in 21 patients with chronic pancreatitis and in 6 patients with previous pancreaticoduodenectomy. Eighteen of the 21 with chronic pancreatitis and all 6 with pancreaticoduodenectomy had abnormally low serum PP-responses to the standard test meal, while all patients with a history of acute pancreatitis had normal postprandial increases in serum PP. The impaired serum PP-responses to food in patients with chronic pancreatitis were not related to the aetiology of pancreatitis, to glucose tolerance, to exocrine pancreatic function (absorption of fat) or to pancreatic calcifications. It is concluded that impaired postprandial serum PP responses in patients with pancreatitis indicate damage to the pancreas.

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“…The existence of such an influence is supported mainly by the notion that pancreatic insufficiency is followed by anatomopathologic alterations of the islets of Langerhans [57] and frequently by overt diabetes [3,58,59]. Thus, from an anatomical point of view, apart from the well-known ªislet-acinar axisº, an ªacinar-islet axisº (including the duct system) could also exist closing the circle of interactions among the components of the pancreas as previously suggested [3].…”

Section: Discussionmentioning

confidence: 82%

Association between islets of Langerhans and pancreatic ductal system in adult rat. Where endocrine and exocrine meet together?

et al. 2001

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It is common to describe the endocrine and the exocrine pancreas as if they were two distinct and independent entities. However the pancreas is an integrated organ involved in the digestion and absorption of nutrients on the one hand, and in the regulation of blood glucose homeostasis, on the other. Most probably, the unique anatomical architecture of this organ, characterized by the dispersion of the endocrine component throughout the acinar parenchyma as hundreds of thousands variable-sized clusters of endocrine cells (islets of Langerhans), has evolved to facilitate interactions between the two glandular components [1]. In order to determine reciprocal influences, many aspects of the relations occurring between exocrine and endocrine pancreas have been investigated in the past three decades [2,3]. Because of the observation that, in contrast to ªtele-insularº acini, ªperi-insularº acini are formed by larger cells, containing more zymogen granules [2, 4±6], numerous studies have addressed the role(s) played by the islet hormones in tuning acinar cell secretion and the anatomical pathways, the so called ªislet-acinar axisª, through which this influence is exerted [2,3,7]. A large body of evidence indicates that a continuous insulo-acinar venous portal system conveys hormone enriched blood from the islets to the acinar parenchyma [2, 3, 8, 9]. The amount of acinar tissue that is ac- Diabetologia (2001) 44: 575±584 Association between islets of Langerhans and pancreatic ductal system in adult rat. Where endocrine and exocrine meet together? AbstractAims/hypothesis. Studies on the functional and morphological relations between exocrine and endocrine pancreas have been conducted mainly to disclose the influence of islets of Langerhans on acinar parenchyma. Less attention has been paid to the relations occurring between islets and pancreatic ducts. Methods. A series of consecutive sections of normal adult rat pancreas were double stained with islet (hormones) and duct (cytokeratin 20) markers. Electron microscopy was conducted to investigate the ultrastructural features of duct-islet relations and anti-insulin immunogold labelling was carried out to reveal the presence of insulin in the pancreatic duct system. Results. Consecutive double-stained sections demonstrated that 73.60 2.97 % of the islets were attached to the ducts. For each series, 93.48 5.43 % of the islets contacting the duct tree were associated with small-sized ducts or centroacinar cells. Electron microscopy revealed that some insulin and somatostatin cells do face the duct lumen. Insulin was detected within the duct lumen and in the endosomal compartment of the duct cells. Conclusions/interpretation. The finding that most islets are connected with the duct system in the adult pancreas is discussed in terms of hormone secretion into the ducts, islet histogenesis and the relation among the three tissue components of the pancreas, the endocrine, the exocrine and the duct system. [Diabetologia (2001) 44: 575±584]

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The endocrine pancreas in chronic pancreatitis

Cited by 127 publications

References 27 publications

Modulation of rat pancreatic acinoductal transdifferentiation and expression of PDX-1 in vitro

Modulation of rat pancreatic acinoductal transdifferentiation and expression of PDX-1 in vitro

Basal and postprandial serum concentrations of pancreatic polypeptide in pancreatitis and after pancreaticoduodenectomy

Association between islets of Langerhans and pancreatic ductal system in adult rat. Where endocrine and exocrine meet together?

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