help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fernandes, A.
Right arrow Articles by Teitelman, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fernandes, A.
Right arrow Articles by Teitelman, G.
Endocrinology Vol. 138, No. 4 1750-1762
Copyright © 1997 by The Endocrine Society


ARTICLES

Differentiation of New Insulin-Producing Cells Is Induced by Injury in Adult Pancreatic Islets1

A. Fernandes, L. C. King, Y. Guz, R. Stein, C. V. E. Wright and G. Teitelman

Department of Anatomy and Cell Biology (A.F., L.C.K., Y.G., G.T.), SUNY Health Science Center at Brooklyn, Brooklyn, New York 11203; Department of Cell Biology (C.V.E.W.), Vanderbilt University Medical Center, Nashville, Tennessee 37232; and the Department of Molecular Physiology and Biophysics (R.S.), Vanderbilt University Medical Center, Nashville, Tennessee 37232

Address all correspondence and requests for reprints to: Dr. Gladys Teitelman, Department of Anatomy and Cell Biology, SUNY Health Science Center at Brooklyn, Brooklyn, New York 11203.

The ability of the adult pancreas to generate new insulin (ß) cells has been controversial because of difficulties in unequivocally identifying the precursor population. We recently determined that ß cells were generated during development from precursors that expressed the homeodomain-containing transcription factor pancreas duodenum homeobox gene-1 (PDX-1). To investigate whether PDX-1+ stem cells are present in adult pancreas, we examined two animal models of diabetes. One model was produced by injecting adult mice with streptozotocin (SZ), a toxin that produces hyperglycemia due to rapid and massive ß cell death. After SZ-mediated elimination of existing IN+/PDX-1+ cells, a population of somatostatin (SOM)+/PDX-1+ cells, a cell type thought to represent an embryonic islet precursor cell, appeared in islets. The appearance of SOM+/PDX-1+ cells was followed in time by the differentiation to SOM+/IN+/PDX-1+cells. SOM+/PDX-1+ cells also appeared in islets of nonobese diabetic mice, a strain of mice in which ß cell destruction is immune-mediated. Our findings establish the existence of PDX-1+ ß cell precursors in the adult pancreas and indicate that their differentiation is induced by islet injury .




This article has been cited by other articles:


Home page
EndocrinologyHome page
Y. Sun, L. Zhang, H. F. Gu, W. Han, M. Ren, F. Wang, B. Gong, L. Wang, H. Guo, W. Xin, et al.
Peroxisome Proliferator-Activated Receptor-{alpha} Regulates the Expression of Pancreatic/Duodenal Homeobox-1 in Rat Insulinoma (INS-1) Cells and Ameliorates Glucose-Induced Insulin Secretion Impaired by Palmitate
Endocrinology, February 1, 2008; 149(2): 662 - 671.
[Abstract] [Full Text] [PDF]


Home page
J. Histochem. Cytochem.Home page
M. Kodama, F. Takeshita, S. Kanegasaki, T. Ochiya, and G. Quinn
Pancreatic Endocrine and Exocrine Cell Ontogeny From Renal Capsule transplanted Embryonic Stem Cells in Streptozocin-injured Mice
J. Histochem. Cytochem., January 1, 2008; 56(1): 33 - 44.
[Abstract] [Full Text] [PDF]


Home page
Mol. Endocrinol.Home page
S. Hanley and L. Rosenberg
Transforming Growth Factor {beta} Is a Critical Regulator of Adult Human Islet Plasticity
Mol. Endocrinol., June 1, 2007; 21(6): 1467 - 1477.
[Abstract] [Full Text] [PDF]


Home page
DiabetesHome page
D. Yin, J. Tao, D. D. Lee, J. Shen, M. Hara, J. Lopez, A. Kuznetsov, L. H. Philipson, and A. S. Chong
Recovery of Islet {beta}-Cell Function in Streptozotocin- Induced Diabetic Mice: An Indirect Role for the Spleen
Diabetes, December 1, 2006; 55(12): 3256 - 3263.
[Abstract] [Full Text] [PDF]


Home page
Poult. Sci.Home page
S. P. Datar, D. S. Suryavanshi, and R. R. Bhonde
Chick Pancreatic B Islets as an Alternative In Vitro Model for Screening Insulin Secretagogues
Poult. Sci., December 1, 2006; 85(12): 2260 - 2264.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
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]


Home page
DiabetesHome page
K. Oyama, K. Minami, K. Ishizaki, M. Fuse, T. Miki, and S. Seino
Spontaneous Recovery From Hyperglycemia by Regeneration of Pancreatic {beta}-Cells in Kir6.2G132S Transgenic Mice.
Diabetes, July 1, 2006; 55(7): 1930 - 1938.
[Abstract] [Full Text] [PDF]


Home page
EndocrinologyHome page
S. Thyssen, E. Arany, and D. J. Hill
Ontogeny of Regeneration of {beta}-Cells in the Neonatal Rat after Treatment with Streptozotocin
Endocrinology, May 1, 2006; 147(5): 2346 - 2356.
[Abstract] [Full Text] [PDF]


Home page
Annals of Clinical & Laboratory ScienceHome page
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]


Home page
DiabetesHome page
A. Suzuki, H. Nakauchi, and H. Taniguchi
Prospective Isolation of Multipotent Pancreatic Progenitors Using Flow-Cytometric Cell Sorting
Diabetes, August 1, 2004; 53(8): 2143 - 2152.
[Abstract] [Full Text] [PDF]


Home page
DiabetesHome page
L. Li, Z. Yi, M. Seno, and I. Kojima
Activin A and Betacellulin: Effect on Regeneration of Pancreatic {beta}-Cells in Neonatal Streptozotocin-Treated Rats
Diabetes, March 1, 2004; 53(3): 608 - 615.
[Abstract] [Full Text] [PDF]


Home page
DiabetesHome page
A. Lechner, Y.-G. Yang, R. A. Blacken, L. Wang, A. L. Nolan, and J. F. Habener
No Evidence for Significant Transdifferentiation of Bone Marrow Into Pancreatic {beta}-Cells In Vivo
Diabetes, March 1, 2004; 53(3): 616 - 623.
[Abstract] [Full Text] [PDF]


Home page
ANN INTERN MEDHome page
A. Kuroda, Y. Yamasaki, and A. Imagawa
{beta}-Cell Regeneration in a Patient with Type 1 Diabetes Mellitus Who Was Receiving Immunosuppressive Therapy
Ann Intern Med, November 18, 2003; 139(10): W-81 - W-81.
[Full Text] [PDF]


Home page
Am. J. Physiol. Endocrinol. Metab.Home page
L. Li, M. Seno, H. Yamada, and I. Kojima
Betacellulin improves glucose metabolism by promoting conversion of intraislet precursor cells to {beta}-cells in streptozotocin-treated mice
Am J Physiol Endocrinol Metab, September 1, 2003; 285(3): E577 - E583.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
I. Ber, K. Shternhall, S. Perl, Z. Ohanuna, I. Goldberg, I. Barshack, L. Benvenisti-Zarum, I. Meivar-Levy, and S. Ferber
Functional, Persistent, and Extended Liver to Pancreas Transdifferentiation
J. Biol. Chem., August 22, 2003; 278(34): 31950 - 31957.
[Abstract] [Full Text] [PDF]


Home page
DiabetesHome page
B. Duvillie, M. Attali, V. Aiello, E. Quemeneur, and R. Scharfmann
Label-Retaining Cells in the Rat Pancreas: Location and Differentiation Potential in Vitro
Diabetes, August 1, 2003; 52(8): 2035 - 2042.
[Abstract] [Full Text] [PDF]


Home page
EndocrinologyHome page
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 page
DevelopmentHome page
G. Gu, J. Dubauskaite, and D. A. Melton
Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and are distinct from duct progenitors
Development, March 7, 2003; 129(10): 2447 - 2457.
[Abstract] [Full Text] [PDF]


Home page
DiabetesHome page
J. A. Pospisilik, J. Martin, T. Doty, J. A. Ehses, N. Pamir, F. C. Lynn, S. Piteau, H.-U. Demuth, C. H.S. McIntosh, and R. A. Pederson
Dipeptidyl Peptidase IV Inhibitor Treatment Stimulates {beta}-Cell Survival and Islet Neogenesis in Streptozotocin-Induced Diabetic Rats
Diabetes, March 1, 2003; 52(3): 741 - 750.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Endocrinol. Metab.Home page
A. Lechner and J. F. Habener
Stem/progenitor cells derived from adult tissues: potential for the treatment of diabetes mellitus
Am J Physiol Endocrinol Metab, February 1, 2003; 284(2): E259 - E266.
[Abstract] [Full Text] [PDF]


Home page
EndocrinologyHome page
Y.-Q. Zhang, H. Zhang, A. Maeshima, H. Kurihara, J.-i. Miyagawa, T. Takeuchi, and I. Kojima
Up-Regulation of the Expression of Activins in the Pancreatic Duct by Reduction of the {beta}-Cell Mass
Endocrinology, September 1, 2002; 143(9): 3540 - 3547.
[Abstract] [Full Text] [PDF]


Home page
DiabetesHome page
M. Lipsett and D. T. Finegood
{beta}-Cell Neogenesis During Prolonged Hyperglycemia in Rats
Diabetes, June 1, 2002; 51(6): 1834 - 1841.
[Abstract] [Full Text] [PDF]


Home page
Mol. Endocrinol.Home page
H.-p. Huang, K. Chu, E. Nemoz-Gaillard, D. Elberg, and M.-J. Tsai
Neogenesis of {beta}-Cells in Adult BETA2/NeuroD-Deficient Mice
Mol. Endocrinol., March 1, 2002; 16(3): 541 - 551.
[Abstract] [Full Text] [PDF]


Home page
Circ. Res.Home page
J. L. Hall, C. M. Matter, X. Wang, and G. H. Gibbons
Hyperglycemia Inhibits Vascular Smooth Muscle Cell Apoptosis Through a Protein Kinase C-Dependent Pathway
Circ. Res., September 29, 2000; 87(7): 574 - 580.
[Abstract] [Full Text] [PDF]


Home page
EndocrinologyHome page
R. Seijffers, O. Ben-David, Y. Cohen, A. Karasik, M. Berezin, C. B. Newgard, and S. Ferber
Increase in PDX-1 Levels Suppresses Insulin Gene Expression in RIN 1046-38 Cells
Endocrinology, July 1, 1999; 140(7): 3311 - 3317.
[Abstract] [Full Text]


Home page
Ann. N. Y. Acad. Sci.Home page
R. JESNOWSKI, P. MULLER, W. SCHARECK, S. LIEBE, and M. LOHR
Immortalized Pancreatic Duct Cells in vitro and in vivo
Ann. N.Y. Acad. Sci., June 30, 1999; 880(1): 50 - 65.
[Abstract] [Full Text] [PDF]


Home page
EndocrinologyHome page
J. Petrik, E. Arany, T. J. McDonald, and D. J. Hill
Apoptosis in the Pancreatic Islet Cells of the Neonatal Rat Is Associated with a Reduced Expression of Insulin-Like Growth Factor II that May Act as a Survival Factor
Endocrinology, June 1, 1998; 139(6): 2994 - 3004.
[Abstract] [Full Text] [PDF]


Home page
EndocrinologyHome page
D. J. Gross, L. Weiss, I. Reibstein, J. van den Brand, H. Okamoto, A. Clark, and S. Slavin
Amelioration of Diabetes in Nonobese Diabetic Mice with Advanced Disease by Linomide-Induced Immunoregulation Combined with Reg Protein Treatment
Endocrinology, May 1, 1998; 139(5): 2369 - 2374.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1997 by The Endocrine Society