Is the rat pancreas an appropriate model of the human pancreas?

Case, R. M.

doi:10.1159/000091849

Cited by 41 publications

(40 citation statements)

References 66 publications

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“…28 However, evidence is accumulating to suggest that the non-human pancreas is not always an appropriate model to study phenomena occurring in the human organ. 60 For example, recent reports aimed at elucidating the islet regenerative response in humans and mice indicated that humans increase b-cell mass primarily through neogenesis, 2 whereas the mouse regenerative response involves b-cell replication. 32 Likewise, cultured human islets have been reported to form precursor cell cultures that can be induced to redifferentiate into islet-like structures.…”

Section: Discussionmentioning

confidence: 99%

Cellular origins of adult human islet in vitro dedifferentiation

Hanley

Pilotte

Massie

et al. 2008

Laboratory Investigation

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Cultured human islets can be dedifferentiated to duct-like structures composed mainly of cytokeratin þ and nestin þ cells. Given that these structures possess the potential to redifferentiate into islet-like structures, we sought to elucidate their specific cellular origins. Adenoviral vectors were engineered for b-, a-, d-or PP-cell-specific GFP expression. A doublestranded system was designed whereby cultures were infected with two vectors: one expressed GFP behind the cumateinducible promoter sequence, and the other expressed the requisite transactivator behind the human insulin, glucagon, somatostatin or pancreatic polypeptide promoter. This system labels hormone þ cells in the islet in a cell-specific manner, allowing these cells to be tracked during the course of transformation from islet to duct-like structure. Post-infection, islets were cultured to induce dedifferentiation. Fluorescence microscopy demonstrated that a-, d-and PP-cells contributed equally to the cytokeratin þ population, with minimal b-cell contribution, whereas the converse was true for nestin þ cells. Complementary targeted cell ablation studies, using streptozotocin or similar adenoviral expression of the Bax (Bcl2-associated X protein) toxigene, validated these findings and suggested a redundancy between a-, d-and PP-cells with respect to cytokeratin þ cell derivation. These results call into question the traditional understanding of islet cells as being terminally differentiated and provide support for the concept of adult islet morphogenetic plasticity.

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Section: Discussionmentioning

confidence: 99%

Cellular origins of adult human islet in vitro dedifferentiation

Hanley

Pilotte

Massie

et al. 2008

Laboratory Investigation

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“…Unfortunately, the extent to which different transport pathways are involved in secretion varies significantly between species. This explains why the maximum pancreatic bicarbonate secretion in the rat (and probably also the mouse) is around 70 mM compared with around 140 mM in the human and in laboratory species such as the guinea pig [2,3] and why, therefore, rat and mouse pancreatic ducts represent poor models of human duct cell function [4].…”

Section: Introductionmentioning

confidence: 99%

Vectorial Bicarbonate Transport by Capan-1 Cells: a Model for Human Pancreatic Ductal Secretion

Szücs

Demeter

Burghardt

et al. 2006

Cell Physiol Biochem

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Human pancreatic ducts secrete a bicarbonate-rich fluid but our knowledge of the secretory process is based mainly on studies of animal models. Our aim was to determine whether the HCO₃^- transport mechanisms in a human ductal cell line are similar to those previously identified in guinea-pig pancreatic ducts. Intracellular pH was measured by microfluorometry in Capan-1 cell monolayers grown on permeable filters and loaded with BCECF. Epithelial polarization was assessed by immunolocalization of occludin. Expression of mRNA for key electrolyte transporters and receptors was evaluated by RT-PCR. Capan-1 cells grown on permeable supports formed confluent, polarized monolayers with well developed tight junctions. The recovery of pH_i from an acid load, induced by a short NH₄⁺ pulse, was mediated by Na⁺-dependent transporters located exclusively at the basolateral membrane. One was independent of HCO₃^- and blocked by EIPA (probably NHE1) while the other was HCO₃^--dependent and blocked by H₂DIDS (probably pNBC1). Changes in pH_i following blockade of basolateral HCO₃^- accumulation confirmed that the cells achieve vectorial HCO₃^- secretion. Dose-dependent increases in HCO₃^- secretion were observed in response to stimulation of both secretin and VPAC receptors. ATP and UTP applied to the apical membrane stimulated HCO₃^- secretion but were inhibitory when applied to the basolateral membrane. HCO₃^- secretion in guinea-pig ducts and Capan-1 cell monolayers share many common features, suggesting that the latter is an excellent model for studies of human pancreatic HCO₃^- secretion.

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“…However, due the lack of a suitable experimental model, and to concentrate on the tissue effects with a simple model to minimize any confounding factors, suturing alone was studied. Even though the anatomy and function of rat pancreas is somewhat different from human [14], the basic acute injury reaction in terms of histology can be well studied in the present model, as previously described [7]. Therefore, we chose to study suturing exposure with different levels of invasiveness rather than to compare various suturing techniques used in pancreatic surgery.…”

Section: Discussionmentioning

confidence: 99%

Effects of Diameter, Number and Tightness of Sutures on Pancreatic Injury Response

Lämsä¹,

Jin²,

Nordback³

et al. 2008

Dig Surg

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Background: We have experimental data indicating that the pancreas is easily damaged by any intervention. The present study compared the effects of suture diameter, number of needle passes and suture tightness on rat pancreas. Methods: Under anesthesia, rat pancreas was sutured either with one loose stitch of 6-0 polydioxanone (PDS II) or 3-0 PDS II, with 5 passes of loose running 6-0 PDS II, or with 6-0 PDS II loop tightened to 0.6 or 1.2 N. Amylase activity and pancreatic tissue histology at the suturing site and farther away, were evaluated 1, 3, 7 and 21 days postoperatively. Results: Each suturing exposure and the sham-operation induced temporary amylase activity elevation on day 1 when compared with the baseline. In histology, 3-0 suture, 5 needle passes and 1.2-newton loop induced more damage than 6-0 suture, single needle pass and 0.6-newton loop, respectively. Similar but milder changes were observed in samples from the remote site. Conclusions: The pancreas reacts to suturing with widespread injury response resembling that of acute pancreatitis. In attempting to reduce suturing-induced widespread injury, as few and thin sutures and as loose suture tightness as possible should be used. Although these findings may seem obvious, they have not previously been proven in terms of histology.

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Is the rat pancreas an appropriate model of the human pancreas?

Cited by 41 publications

References 66 publications

Cellular origins of adult human islet in vitro dedifferentiation

Cellular origins of adult human islet in vitro dedifferentiation

Vectorial Bicarbonate Transport by Capan-1 Cells: a Model for Human Pancreatic Ductal Secretion

Effects of Diameter, Number and Tightness of Sutures on Pancreatic Injury Response

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