|
 |
|
|||||||
|
|||||||||
Diabetes 51:1834-1841, 2002
© 2002 by the American Diabetes Association, Inc.
ß-Cell Neogenesis During Prolonged Hyperglycemia in Rats
From the Diabetes Research Laboratory, School of Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada
ß-cell neogenesis from ductal precursors, and possibly from other pancreatic cell types, contributes to the expansion of ß-cell mass during development and after diabetogenic insults in rodents. Using a mathematical model-based analysis of ß-cell mass, replication, and size, we recently demonstrated that neogenesis is also quantitatively important to the expansion of ß-cell mass during prolonged hyperglycemia. In the present study, we examined the morphological appearance of neogenic focal areas, duct cell replication, and ß-cell cluster size distribution in male Sprague Dawley rats infused with either saline or 50% glucose (2 ml/h) for 0, 1, 2, 3, 4, 5, or 6 days. Pancreatic tissue characterized by a high density of small duct-like structures, previously described as neogenic focal areas, were present in glucose-infused rats after 2, 3, or 4 days of infusion. The cross-sectional area of the pancreas characterized as focal tissue peaked after 3 days of infusion at 2.9 ± 0.8%. In contrast to the partial pancreatectomy model of ß-cell regeneration, duct cell replication was not increased before or during focal area formation. However, the replication rate of cells in the duct-like structures of the focal areas was twofold greater than in cells of the common pancreatic duct and 15- to 40-fold greater than in cells of small, medium, and large ducts. Duct-cell replication was significantly reduced in small, medium, and large ducts of glucose as compared to saline-infused rats (0.21 ± 0.02 vs. 0.48 ± 0.04%; P < 0.03). Duct-associated ß-cell mass was not different in glucose- and saline-infused rats (P = 0.78), whereas the number of acinar-associated single ß -cells increased by 70% after 3 and 4 days of glucose infusion. In addition to small duct-like structures, focal areas had considerable T-cell infiltration (151 ± 30 T-cells/ mm2). There was also an increase in T-cell infiltration in acinar tissue of glucose as compared to saline-infused rats (0.43 ± 0.11 vs. 0.03 ± 0. 01 T-cells/mm2; P < 0.0001). In conclusion, these data suggest that neogenic focal areas in these glucose-infused rats do not arise from replication and differentiation of ductal progenitor cells. Rather, acinar cell transdifferentiation into ß-cells and acinar cell dedifferentiation into neogenic focal areas lead to new ß-cell formation during prolonged hyperglycemia.
CiteULike 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  L. C. Alonso, T. Yokoe, P. Zhang, D. K. Scott, S. K. Kim, C. P. O'Donnell, and A. Garcia-Ocana Glucose Infusion in Mice: A New Model to Induce {beta}-Cell Replication Diabetes, July 1, 2007; 56(7): 1792 - 1801. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Peshavaria, B. L. Larmie, J. Lausier, B. Satish, A. Habibovic, V. Roskens, K. LaRock, B. Everill, J. L. Leahy, and T. L. Jetton Regulation of Pancreatic {beta}-Cell Regeneration in the Normoglycemic 60% Partial-Pancreatectomy Mouse Diabetes, December 1, 2006; 55(12): 3289 - 3298. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Hussain, D. L. Porras, M. H. Rowe, J. R. West, W.-J. Song, W. E. Schreiber, and F. E. Wondisford Increased Pancreatic {beta}-Cell Proliferation Mediated by CREB Binding Protein Gene Activation Mol. Cell. Biol., October 15, 2006; 26(20): 7747 - 7759. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Narang and R. I. Mahato Biological and biomaterial approaches for improved islet transplantation. Pharmacol. Rev., June 1, 2006; 58(2): 194 - 243. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Lu, Z. Wang, and M. Zhu Human bone marrow mesenchymal stem cells transfected with human insulin genes can secrete insulin stably. Ann. Clin. Lab. Sci., March 1, 2006; 36(2): 127 - 136. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Kwon, C. A. Marshall, H. Liu, K. L. Pappan, M. S. Remedi, and M. L. McDaniel Glucose-stimulated DNA Synthesis through Mammalian Target of Rapamycin (mTOR) Is Regulated by KATP Channels: EFFECTS ON CELL CYCLE PROGRESSION IN RODENT ISLETS J. Biol. Chem., February 10, 2006; 281(6): 3261 - 3267. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Bottino and M. Trucco Multifaceted Therapeutic Approaches for a Multigenic Disease Diabetes, December 1, 2005; 54(suppl_2): S79 - S86. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Holland, L. J. Gonez, G. Naselli, R. J. MacDonald, and L. C. Harrison Conditional Expression Demonstrates the Role of the Homeodomain Transcription Factor Pdx1 in Maintenance and Regeneration of {beta}-Cells in the Adult Pancreas Diabetes, September 1, 2005; 54(9): 2586 - 2595. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. L. Jetton, J. Lausier, K. LaRock, W. E. Trotman, B. Larmie, A. Habibovic, M. Peshavaria, and J. L. Leahy Mechanisms of Compensatory {beta}-Cell Growth in Insulin-Resistant Rats: Roles of Akt Kinase Diabetes, August 1, 2005; 54(8): 2294 - 2304. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Bock, B. Pakkenberg, and K. Buschard Genetic Background Determines the Size and Structure of the Endocrine Pancreas Diabetes, January 1, 2005; 54(1): 133 - 137. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Paris, C. Bernard-Kargar, M.-F. Berthault, L. Bouwens, and A. Ktorza Specific and Combined Effects of Insulin and Glucose on Functional Pancreatic {beta}-Cell Mass in Vivo in Adult Rats Endocrinology, June 1, 2003; 144(6): 2717 - 2727. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Diabetes | Diabetes Care | Clinical Diabetes | Diabetes Spectrum |