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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...

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Autores principales: 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.
Formato: Texto
Lenguaje:English
Publicado: American Diabetes Association 2008
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.
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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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