Islet cell neogenesis in the pancreas

Bouwens, Luc; Klöppel, Günter

doi:10.1007/bf00202885

Cited by 90 publications

(82 citation statements)

References 58 publications

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“…As early as 21.5 days post coïtum, GK fetuses exhibited a lower pancreatic weight and total pancreatic beta-cell mass, the value of this last parameter representing in the GK fetuses only 23 % of that of normal fetuses. It is known that the development of beta cells during intrauterine life mainly relies upon the neogenesis of beta cell from the putative precursor cells [27,28]. One might suggest that a shortage of these putative cells at the early stage of development associated with the possible alteration of proliferative capacity of the beta cells could be a cause of the deficiency of the beta-cell mass observed in the 21.5-day-old GK fetuses.…”

Section: Discussionmentioning

confidence: 99%

Impaired development of pancreatic beta-cell mass is a primary event during the progression to diabetes in the GK rat

et al. 1997

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Established non-insulin-dependent diabetes mellitus (NIDDM) is associated with profound insulin secretory defects that occur together with insulin resistance. The basis for the insulin secretory defects is unknown and is difficult to study in human subjects because it is not possible to identify prospectively those subjects in whom glucose control will deteriorate. The fact that total beta-cell mass is decreased in NIDDM patients compared to weight-matched control subjects [1] offers strong support for the notion that insulin production may become insufficient if beta-cell growth is deficient. The contribution of decreased beta-cell mass to deficient insulin secretion Diabetologia (1997) 40: 916-925 Impaired development of pancreatic beta-cell mass is a primary event during the progression to diabetes in the GK rat

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Section: Discussionmentioning

confidence: 99%

Impaired development of pancreatic beta-cell mass is a primary event during the progression to diabetes in the GK rat

et al. 1997

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“…It is hypothesised that in these conditions mature duct cells can transiently regain a more pluripotent phenotype [36] and ultimately differentiate into endocrine cells. Some external stimuli can enhance the endocrine differentiation process [36,40]. It is therefore interesting to in-vestigate the effect of KGF using the above models of adult pancreas regeneration in which there seem to be a recapitulation of embryonic development.…”

Section: Effect Of Kgf On Beta Cell and Ductal Cell Proliferationmentioning

confidence: 99%

Keratinocyte growth factor and beta-cell differentiation in human fetal pancreatic endocrine precursor cells

et al. 2003

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Aims and hypothesis. Keratinocyte growth factor (KGF) is a member of the heparin-binding fibroblast growth factor family with a high degree of specificity for epithelial cells in vitro and in vivo. Our aim was to study the effect of KGF on beta-cell growth and differentiation on islet-like cell clusters derived from human fetal pancreas. Methods. We investigated the effects of KGF, in vitro, on beta-cell differentiation from undifferentiated pancreatic precursor cells and in vivo after transplantating human fetal pancreatic cells into athymic rats treated with KGF. Results. Treatment of islet-like cell clusters with KGF in vitro did not change the number of insulin producing cells, as measured by the measurement of insulin content or DNA. The in vivo treatment of recipient rats with KGF increased the number of beta cells within the grafts 8 weeks after transplantation. At this time, glucose-stimulated insulin secretion was evaluated by glucose stimulation tests in rats bearing the transplants. Measurements of human C-peptide concentrations after glucose challenge showed that the newly differentiated beta cells in the KGF-treated group were functionally competent as opposed to the control group, where the graft failed to release insulin appropriately. Conclusion/interpretation. These findings suggest that in vivo, KGF is capable of inducing human fetal beta-cell expansion. The growth promoting effect of KGF on beta cells occurred mainly through the activation of ductal cell proliferation and their subsequent differentiation into beta cells. [Diabetologia (2003) 46:822-829]

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“…This problem could be solved by finding ways of generating more islet cells from the available pancreatic tissue, by the process of neogenesis [2,3] or by stimulating proliferation of beta cells [4]. Despite much progress in our understanding of pancreas development during the last decade, the extracellular factors that specify islet cell differentiation in the embryo remain unknown [5].…”

Section: Introductionmentioning

confidence: 99%

“…Despite much progress in our understanding of pancreas development during the last decade, the extracellular factors that specify islet cell differentiation in the embryo remain unknown [5]. In adult mammals, the endocrine pancreas can expand or regenerate under certain experimental conditions, either as a result of islet cell proliferation [4], or neogenesis from progenitor cells [3,[6][7][8]. In vitro, very few studies have been able to demonstrate the feasibility of inducing islet neogenesis from adult tissue.…”

Section: Introductionmentioning

confidence: 99%

In vitro generation of insulin-producing beta cells from adult exocrine pancreatic cells

Baeyens¹,

Breuck²,

Lardon³

et al. 2004

Diabetologia

Self Cite

289

224

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Aims/hypothesis: Transplantation of insulinproducing beta cells from donors can cure diabetes, but they are available in insufficient quantities. In this study, we investigated the possibility of generating insulinproducing cells from adult rat exocrine cells cultured in the presence of growth factors. Methods: Rat exocrine pancreatic cells were isolated and treated in vitro with epidermal growth factor (EGF) and leukaemia inhibitory factor (LIF). Analysis was performed by immunocytochemistry, DNA measurement and radioimmunoassay. Cells were transplanted to alloxan-treated (70 mg/kg) nude mice and glycaemia was monitored for 21 days. Nephrectomy was performed on day 15. Results: In a 3-day culture period, addition of LIF plus EGF to the medium resulted in an 11-fold increase of the beta cell mass. This could not be attributed to the very low mitotic activity of contaminating beta cells. Furthermore, when contaminating beta cells were initially destroyed with alloxan, this effect was even more pronounced. The newly formed cells secreted insulin in response to glucose and were immunoreactive for C-peptide-I, Pdx-1 and GLUT-2, which are characteristics of mature beta cells. Electron microscopy showed that they also contained insulinimmunoreactive secretory granules. Some insulin-positive cells were immunoreactive for amylase and cytokeratin-20, or were binucleated, which are characteristics of exocrine cells. The cells were able to restore normoglycaemia when transplanted to alloxan-diabetic mice, and hyperglycaemia recurred upon removal of the graft. Conclusions/interpretation: Our study shows that functional beta cells can be generated from exocrine tissue by transdifferentiation and thereby may offer a new perspective for beta cell therapy.

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Islet cell neogenesis in the pancreas

Cited by 90 publications

References 58 publications

Impaired development of pancreatic beta-cell mass is a primary event during the progression to diabetes in the GK rat

Impaired development of pancreatic beta-cell mass is a primary event during the progression to diabetes in the GK rat

Keratinocyte growth factor and beta-cell differentiation in human fetal pancreatic endocrine precursor cells

In vitro generation of insulin-producing beta cells from adult exocrine pancreatic cells

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