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Postnatal Expansion of the Pancreatic β-Cell Mass Is Dependent on Survivin
OBJECTIVE—Diabetes results from a deficiency of functional β-cells due to both an increase in β-cell death and an inhibition of β-cell replication. The molecular mechanisms responsible for these effects in susceptible individuals are mostly unknown. The objective of this study was to determine wheth...
Autores principales: | , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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American Diabetes Association
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2551682/ https://www.ncbi.nlm.nih.gov/pubmed/18599523 http://dx.doi.org/10.2337/db08-0170 |
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author | Jiang, Yuying Nishimura, Wataru Devor-Henneman, Deborah Kusewitt, Donna Wang, Haijuan Holloway, Michael P. Dohi, Takehiko Sabo, Edmond Robinson, Michael L. Altieri, Dario C. Sharma, Arun Altura, Rachel A. |
author_facet | Jiang, Yuying Nishimura, Wataru Devor-Henneman, Deborah Kusewitt, Donna Wang, Haijuan Holloway, Michael P. Dohi, Takehiko Sabo, Edmond Robinson, Michael L. Altieri, Dario C. Sharma, Arun Altura, Rachel A. |
author_sort | Jiang, Yuying |
collection | PubMed |
description | OBJECTIVE—Diabetes results from a deficiency of functional β-cells due to both an increase in β-cell death and an inhibition of β-cell replication. The molecular mechanisms responsible for these effects in susceptible individuals are mostly unknown. The objective of this study was to determine whether a gene critical for cell division and cell survival in cancer cells, survivin, might also be important for β-cells. RESEARCH DESIGN AND METHODS—We generated mice harboring a conditional deletion of survivin in pancreatic endocrine cells using mice with a Pax-6-Cre transgene promoter construct driving tissue-specific expression of Cre-recombinase in these cells. We performed metabolic studies and immunohistochemical analyses to determine the effects of a mono- and biallelic deletion of survivin. RESULTS—Selective deletion of survivin in pancreatic endocrine cells in the mouse had no discernible effects during embryogenesis but was associated with striking decreases in β-cell number after birth, leading to hyperglycemia and early-onset diabetes by 4 weeks of age. Serum insulin levels were significantly decreased in animals lacking endocrine cell survivin, with relative stability of other hormones. Exogenous expression of survivin in mature β-cells lacking endogenous survivin completely rescued the hyperglycemic phenotype and the decrease in β-cell mass, confirming the specificity of the survivin effect in these cells. CONCLUSIONS—Our findings implicate survivin in the maintenance of β-cell mass through both replication and antiapoptotic mechanisms. Given the widespread involvement of survivin in cancer, a novel role for survivin may well be exploited in β-cell regulation in diseased states, such as diabetes. |
format | Text |
id | pubmed-2551682 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-25516822009-10-01 Postnatal Expansion of the Pancreatic β-Cell Mass Is Dependent on Survivin Jiang, Yuying Nishimura, Wataru Devor-Henneman, Deborah Kusewitt, Donna Wang, Haijuan Holloway, Michael P. Dohi, Takehiko Sabo, Edmond Robinson, Michael L. Altieri, Dario C. Sharma, Arun Altura, Rachel A. Diabetes Islet Studies OBJECTIVE—Diabetes results from a deficiency of functional β-cells due to both an increase in β-cell death and an inhibition of β-cell replication. The molecular mechanisms responsible for these effects in susceptible individuals are mostly unknown. The objective of this study was to determine whether a gene critical for cell division and cell survival in cancer cells, survivin, might also be important for β-cells. RESEARCH DESIGN AND METHODS—We generated mice harboring a conditional deletion of survivin in pancreatic endocrine cells using mice with a Pax-6-Cre transgene promoter construct driving tissue-specific expression of Cre-recombinase in these cells. We performed metabolic studies and immunohistochemical analyses to determine the effects of a mono- and biallelic deletion of survivin. RESULTS—Selective deletion of survivin in pancreatic endocrine cells in the mouse had no discernible effects during embryogenesis but was associated with striking decreases in β-cell number after birth, leading to hyperglycemia and early-onset diabetes by 4 weeks of age. Serum insulin levels were significantly decreased in animals lacking endocrine cell survivin, with relative stability of other hormones. Exogenous expression of survivin in mature β-cells lacking endogenous survivin completely rescued the hyperglycemic phenotype and the decrease in β-cell mass, confirming the specificity of the survivin effect in these cells. CONCLUSIONS—Our findings implicate survivin in the maintenance of β-cell mass through both replication and antiapoptotic mechanisms. Given the widespread involvement of survivin in cancer, a novel role for survivin may well be exploited in β-cell regulation in diseased states, such as diabetes. American Diabetes Association 2008-10 /pmc/articles/PMC2551682/ /pubmed/18599523 http://dx.doi.org/10.2337/db08-0170 Text en Copyright © 2008, American Diabetes Association https://creativecommons.org/licenses/by-nc-nd/3.0/Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Islet Studies Jiang, Yuying Nishimura, Wataru Devor-Henneman, Deborah Kusewitt, Donna Wang, Haijuan Holloway, Michael P. Dohi, Takehiko Sabo, Edmond Robinson, Michael L. Altieri, Dario C. Sharma, Arun Altura, Rachel A. Postnatal Expansion of the Pancreatic β-Cell Mass Is Dependent on Survivin |
title | Postnatal Expansion of the Pancreatic β-Cell Mass Is Dependent on Survivin |
title_full | Postnatal Expansion of the Pancreatic β-Cell Mass Is Dependent on Survivin |
title_fullStr | Postnatal Expansion of the Pancreatic β-Cell Mass Is Dependent on Survivin |
title_full_unstemmed | Postnatal Expansion of the Pancreatic β-Cell Mass Is Dependent on Survivin |
title_short | Postnatal Expansion of the Pancreatic β-Cell Mass Is Dependent on Survivin |
title_sort | postnatal expansion of the pancreatic β-cell mass is dependent on survivin |
topic | Islet Studies |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2551682/ https://www.ncbi.nlm.nih.gov/pubmed/18599523 http://dx.doi.org/10.2337/db08-0170 |
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