Regeneration of Pancreatic β Cells from Intra-Islet Precursor Cells in an Experimental Model of Diabetes

Guz, Yelena; Nasir, Irem; Teitelman, Gladys

doi:10.1210/endo.142.11.8501

Cited by 191 publications

(24 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We previously showed that a dose of 200 mg/Kg of streptozotocin eliminated almost all the beta cells of islets a few hours after it was injected [8]. Few IN+ cells reappear in islets of hyperglycaemic (H) 7-day post-SZ mice (Fig.…”

Section: Insulin-dependent Increase In the Number Of Beta Cellsmentioning

confidence: 90%

“…This antibody is highly specific for the nuclear form of Pdx-1. However, the high sensitivity of the confocal microscope allowed us to distinguish a weak cytoplasmic staining, which was not detected using a microscope with a conventional optical system [8].…”

Section: Methodsmentioning

confidence: 99%

“…These techniques have been described [7,8]. In brief, the sections were incubated sequentially in an empirically derived optimal dilution of control serum or primary antibody raised in species "X" containing 1% goat serum in Tris-saline solution (TS; 0.9% NaCl in 0.1 mol/l Tris, pH 7.4) for 18 h; a 1:50 dilution of anti-(species x) biotinylated IgG solution in 1% goat serum in TS for 30 min; and a 1:100 dilution of peroxidase-avidin complex for 30 min (avidin-biotin complex: ABC technique).…”

Section: Methodsmentioning

confidence: 99%

“…We have reported that newly differentiated beta cells appeared in the pancreases of mice in which diabetes was induced by injecting streptozotocin (SZ), a beta-cell toxin [7]. The re-establishment of normal glucose concentrations by exogenously administered insulin 1 day after the injection of SZ led to an increase in beta-cell neogenesis and to the development of morphologically normal pancreatic islets [8], although the functional capacity of these cells has not been determined. Our results suggested that the new beta cells that appeared There is currently an active search for sources of new beta cells that could be used to replace the original population destroyed by injury or disease [1,2,3,4,5,6].…”

mentioning

confidence: 99%

“…One group of progenitors expressed the glucose transporter 2 (GLUT2) while the second set of beta-cell progenitors coexpressed SOM and Pdx-1, a key transcription factor required for the development of the pancreas and for the regulation of insulin expression [9,10]. We postulated that both GLUT2 and Pdx-1/SOM+ cells matured into GLUT-2+ Pdx-1+ cells containing only insulin [8].…”

mentioning

confidence: 99%

See 4 more Smart Citations

Detrimental effect of protracted hyperglycaemia on beta-cell neogenesis in a mouse murine model of diabetes

2002

View full text Add to dashboard Cite

Aims/hypothesis. Previous studies have shown that new beta cells differentiate from intra-islet precursors in pancreatic islets of mice in which diabetes is induced by injecting a high dose of the beta-cell toxin streptozotocin. Moreover, the re-establishment of euglycaemia by insulin therapy 1 day after streptozotocin treatment improved the process of regeneration. We sought to assess whether a 1-week delay in the restoration of euglycaemia would affect beta-cell regeneration. Methods. Adult CD-1 mice were injected with 200 mg/kg of streptozotocin. One group of mice remained hyperglycaemic throughout the experiment while a second group became normoglycaemic following the administration of insulin therapy 1 week after the injection of streptozotocin. Pancreata removed at different times after treatment were processed for visualization ofβ precursor-cell markers and insulin by confocal microscopy.Results. New beta cells appeared in islets of streptozotocin-treated mice after restoration of normoglycaemia. Like islets of streptozotocin mice in which blood glucose concentrations were rapidly restored, islets of mice that became normoglycaemic 1 week after streptozotocin treatment also had two potential insulin precursor cell types. Protracted hyperglycaemia however, had several harmful effects on insulin cell neogenesis, such as a reduction in the number of euglycaemic mice with successful beta-cell regeneration and a decrease in the number and survival of the newly differentiated insulin-containing cells. Conclusion/interpretation. These results indicate that islets gradually lose their regenerative potential when they are exposed to high circulating glucose concentrations for an extended period of time. [Diabetologia (2002[Diabetologia ( ) 45:1689[Diabetologia ( -1696

show abstract

Section: Insulin-dependent Increase In the Number Of Beta Cellsmentioning

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Detrimental effect of protracted hyperglycaemia on beta-cell neogenesis in a mouse murine model of diabetes

2002

View full text Add to dashboard Cite

show abstract

Development and Life Cycle of a β‐Cell

Serup¹,

Nielsen

2003

International Textbook of Diabetes Mellitus

View full text Add to dashboard Cite

The understanding of the molecular biology of the pancreas β‐cell began 25 years ago with the cloning of the insulin cDNA, followed by the determination of the genomic organization and the identification of multiple cis ‐ and trans ‐acting elements in the 5′‐flanking region. The developmental biology of the pancreas started earlier but was put on hold until the molecular biological technology allowed approaching the questions raised some 30 years ago. A major breakthrough happened 8 years ago when disruption of the gene for an insulin gene transcription factor was found to ablate the development of the pancreas. This has greatly stimulated the search for new transcription factors and their regulation by growth and differentiation factors in order to understand the basal molecular mechanisms involved in the formation of the pancreas β‐cell and the perspectives for prevention, treatment, and cure of diabetes. The maintenance of an appropriate β‐cell mass depends on neogenesis from progenitor cells, proliferation of existing β‐cells, and β‐cell death. The balance between these processes is regulated by a complex interaction of metabolites, hormones, and growth factors. Under normal conditions there appears to be a close correspondence between insulin demand and the functional β‐cell mass. The function of the β‐cell is not only under acute regulation by nutrients following a meal but is also subject to regulation by chronic changes in the insulin demand as in pregnancy or obesity, which result in adjustment of the β‐cell number.

show abstract

Insulin‐Producing Cells Derived from Rat Bone Marrow and Their Autologous Transplantation in the Duodenal Wall for Treating Diabetes

Zhang

Wang

Liu

et al. 2009

The Anatomical Record

View full text Add to dashboard Cite

Islet cell transplantation is one of the most promising therapies for diabetes mellitus (DM). However, the limited availability of purified islets for transplantation and the risk of immunological rejection severely limit its use. In vitro transdifferentiation of autologous bone marrow-derived mesenchymal stem cells (BMSCs) into insulin-producing cells (IPCs) could provide an abundant source of cells for this procedure and avoid immunological rejection. Here, we isolated and characterized BMSCs and induced their in vitro differentiation into IPCs. Reverse-transcription polymerase chain reaction analysis revealed that these IPCs could express Ins1, Ins2, glucagon, glucose transporter 2, and pancreatic duodenal homeobox-1. Insulin production by the IPCs was confirmed by immunocytochemistry and Western blot analysis. On this basis, donor rats supplying BMSCs were made diabetic by a single intraperitoneal injection of streptozotocin. The IPCs were then autologously transplanted into the duodenal submucosa of diabetic rats. Grafted cells could be visualized in sections after 2, 4, and 8 weeks by immunohistochemical staining for insulin. Furthermore, in the IPC-implanted group, hyperglycemia was normalized, compared with a persistent increase in glucose levels in the diabetic group and intraperitoneal glucose tolerance test-induced responses were observed in the IPC-implanted group. These results on autologous transplantation of IPCs derived from BMSCs into the duodenal wall could offer a novel potential therapeutical protocol for DM. Anat Rec, 292:728-735, 2009. V V C 2009 Wiley-Liss, Inc.

show abstract

Regeneration of Pancreatic β Cells from Intra-Islet Precursor Cells in an Experimental Model of Diabetes

Cited by 191 publications

References 35 publications

Detrimental effect of protracted hyperglycaemia on beta-cell neogenesis in a mouse murine model of diabetes

Detrimental effect of protracted hyperglycaemia on beta-cell neogenesis in a mouse murine model of diabetes

Development and Life Cycle of a β‐Cell

Insulin‐Producing Cells Derived from Rat Bone Marrow and Their Autologous Transplantation in the Duodenal Wall for Treating Diabetes

Contact Info

Product

Resources

About