Pancreatic regeneration in type 1 diabetes: dreams on a deserted islet?

Atkinson, Mark A.; Rhodes, Christopher J.

doi:10.1007/s00125-005-1957-2

Cited by 17 publications

(13 citation statements)

References 11 publications

(15 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This indicates that elimination of insulitis plays an important role in augmenting ␤ cell regeneration. It was reported that newly formed ␤ cells were more susceptible to cytokine-induced cell death (17,39). Therefore, we speculate that anti-CD3 conditioning alone may result in control of insulitis via induction of Treg cells in some diabetic mice as described previously (10).…”

Section: Discussionsupporting

confidence: 61%

“…Investigators have been searching for therapies that would support regeneration of islet ␤ cells in type 1 diabetic individuals. Recent studies in animal models as well as patients indicate three potential mechanisms for islet regeneration in type 1 diabetes (17)(18)(19)(20): replication of existing ␤ cells, neogenesis of ␤ cells from pancreatic ductal epithelium stem cells, and transdifferentiation of exocrine into endocrine ␤ cells.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Elimination of insulitis and augmentation of islet β cell regeneration via induction of chimerism in overtly diabetic NOD mice

Zhang

Todorov

Lin

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Type 1 diabetes in both humans and nonobese diabetic (NOD) mice results from autoreactive T cell destruction of insulin-producing ␤ cells. Cure of type 1 diabetes may require both reversal of autoimmunity and regeneration of ␤ cells. Induction of chimerism via allogeneic hematopoietic cell transplantation has been shown to reestablish tolerance in both prediabetic and diabetic NOD mice. However, it is unclear whether this therapy augments ␤ cell regeneration. Furthermore, this procedure usually requires total body irradiation conditioning of recipients. The toxicity of total body irradiation conditioning and potential for graft-versus-host disease (GVHD) limit the application of allogeneic hematopoietic cell transplantation for treating type 1 diabetes. Here we report that injection of donor bone marrow and CD4 ؉ T cell-depleted spleen cells induced chimerism without causing GVHD in overtly diabetic NOD mice conditioned with anti-CD3/CD8 and that induction of chimerism in new-onset diabetic NOD mice led to elimination of insulitis, regeneration of host ␤ cells, and reversal of hyperglycemia. Therefore, this radiation-free GVHD preventive approach for induction of chimerism may represent a viable means for reversing type 1 diabetes.hematopoietic cell transplantation ͉ type 1 diabetes ͉ anti-CD3-conditioning ͉ reversal of diabetes ͉ reversal of autoimmunity

show abstract

Section: Discussionsupporting

confidence: 61%

mentioning

confidence: 99%

Elimination of insulitis and augmentation of islet β cell regeneration via induction of chimerism in overtly diabetic NOD mice

Zhang

Todorov

Lin

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…The results indicate that functional ␤-cell mass was expanded with atorvastatin in both control and STZ-treated neonatal rats and suggests a novel effect of a statin in promoting islet plasticity. endothelial cells; regeneration PANCREATIC ␤-CELL MASS is known to change dynamically in response to altered metabolic demand, and a limited regeneration is possible following ␤-cell destruction (4). Understanding the mechanisms by which ␤-cell mass can be increased offers potential for targeted ␤-cell replacement in diabetes.…”

mentioning

confidence: 99%

Effects of atorvastatin on the regeneration of pancreatic β-cells after streptozotocin treatment in the neonatal rodent

Marchand

Arany

Hill

2010

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Marchand KC, Arany EJ, Hill DJ. Effects of atorvastatin on the regeneration of pancreatic ␤-cells after streptozotocin treatment in the neonatal rodent. Am J Physiol Endocrinol Metab 299: E92-E100, 2010. First published April 13, 2010; doi:10.1152/ajpendo.00132.2010.-To investigate the role of statins in ␤-cell regeneration a model of streptozotocin (STZ)-induced ␤-cell injury was used in the neonatal rat. We hypothesized that ␤-cell growth and regeneration would increase following treatment with atorvastatin and that this would be associated with intraislet vasculogenesis. Pregnant Wistar rats were gavaged with 20 or 40 mg/kg atorvastatin for 21 days commencing on gestation day 15. Atorvastatin was detected in the circulation of the offspring. On postnatal day 4, the pups were given either a control or STZ (70 mg/kg ip) injection. ␤-Cell mass had partially recovered by postnatal day 44 following STZ treatment, and atorvastatin (20 mg/ kg) significantly increased ␤-cell mass in both STZ-treated and control animals. An increase in the numbers of small islets at postnatal day 44 was seen in STZ-treated animals following atorvastatin, suggestive of neogenesis, and glucose tolerance was improved. Treatment with atorvastatin caused an increase in the numbers of intraislet endothelial cells at postnatal day 14 and the percentage of endothelial cells undergoing DNA synthesis, suggesting that angiogenesis had preceded the increase in ␤-cell mass. The results indicate that functional ␤-cell mass was expanded with atorvastatin in both control and STZ-treated neonatal rats and suggests a novel effect of a statin in promoting islet plasticity.

show abstract

“…This notion has, however, recently come under scrutiny following the development of the concept of beta cell regeneration [1]. Evidence supporting a loss of beta cell mass comes from many fields, including incretin pharmacology, stem cell biology, obesity, pregnancy and type 2 diabetes.…”

mentioning

confidence: 99%

Pancreatic adenocarcinoma patients with localised chronic severe pancreatitis show an increased number of single beta cells, without alterations in fractional insulin area

et al. 2008

Self Cite

View full text Add to dashboard Cite

Aims/hypothesis Recent histological analysis of pancreases obtained from patients with long-standing type 1 diabetes identified chronic islet inflammation and limited evidence suggestive of beta cell replication. Studies in rodent models also suggest that beta cell replication can be induced by certain inflammatory cytokines and by gastrin. We therefore tested the hypothesis that beta cell replication is observed in non-autoimmune human pancreatic disorders in which localised inflammation or elevated gastrin levels are present. Methods Resected operative pancreatic specimens were obtained from patients diagnosed with primary adenocarcinoma (with or without chronic severe pancreatitis) or gastrinoma. Additional pancreatic tissue was obtained from autopsy control patients. Immunohistochemistry was used to assess fractional insulin area, beta cell number and replication rate and differentiation factors relevant to beta cell development.Results Fractional insulin area was similar among groups. Patients with pancreatic adenocarcinoma and localised chronic severe pancreatitis displayed significant increases in the number of single beta cells, as well as increased beta cell replication rate and levels of neurogenic differentiation 1 in islets. Patients with gastrinoma demonstrated significant increases in the number of single beta cells, but the beta cell replication rate and islet differentiation factor levels were similar to those in the control group. Conclusions/interpretation These findings indicate that chronic severe pancreatic inflammation can be associated with significant effects on beta cell number or replication rate, depending on the distribution of the cells. This information may prove useful for attempts seeking to design therapies aimed at inducing beta cell replication as a means of reversing diabetes.

show abstract

Pancreatic regeneration in type 1 diabetes: dreams on a deserted islet?

Cited by 17 publications

References 11 publications

Elimination of insulitis and augmentation of islet β cell regeneration via induction of chimerism in overtly diabetic NOD mice

Elimination of insulitis and augmentation of islet β cell regeneration via induction of chimerism in overtly diabetic NOD mice

Effects of atorvastatin on the regeneration of pancreatic β-cells after streptozotocin treatment in the neonatal rodent

Pancreatic adenocarcinoma patients with localised chronic severe pancreatitis show an increased number of single beta cells, without alterations in fractional insulin area

Contact Info

Product

Resources

About