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In Vivo Pancreatic β-Cell–Specific Expression of Antiaging Gene Klotho: A Novel Approach for Preserving β-Cells in Type 2 Diabetes
Protein expression of an antiaging gene, Klotho, was depleted in pancreatic islets in patients with type 2 diabetes mellitus (T2DM) and in db/db mice, an animal model of T2DM. The objective of this study was to investigate whether in vivo expression of Klotho would preserve pancreatic β-cell functio...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375073/ https://www.ncbi.nlm.nih.gov/pubmed/25377875 http://dx.doi.org/10.2337/db14-0632 |
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author | Lin, Yi Sun, Zhongjie |
author_facet | Lin, Yi Sun, Zhongjie |
author_sort | Lin, Yi |
collection | PubMed |
description | Protein expression of an antiaging gene, Klotho, was depleted in pancreatic islets in patients with type 2 diabetes mellitus (T2DM) and in db/db mice, an animal model of T2DM. The objective of this study was to investigate whether in vivo expression of Klotho would preserve pancreatic β-cell function in db/db mice. We report for the first time that β-cell–specific expression of Klotho attenuated the development of diabetes in db/db mice. β-Cell–specific expression of Klotho decreased hyperglycemia and enhanced glucose tolerance. The beneficial effects of Klotho were associated with significant improvements in T2DM-induced decreases in number of β-cells, insulin storage levels in pancreatic islets, and glucose-stimulated insulin secretion from pancreatic islets, which led to increased blood insulin levels in diabetic mice. In addition, β-cell–specific expression of Klotho decreased intracellular superoxide levels, oxidative damage, apoptosis, and DNAJC3 (a marker for endoplasmic reticulum stress) in pancreatic islets. Furthermore, β-cell–specific expression of Klotho increased expression levels of Pdx-1 (insulin transcription factor), PCNA (a marker of cell proliferation), and LC3 (a marker of autophagy) in pancreatic islets in db/db mice. These results reveal that β-cell–specific expression of Klotho improves β-cell function and attenuates the development of T2DM. Therefore, in vivo expression of Klotho may offer a novel strategy for protecting β-cells in T2DM. |
format | Online Article Text |
id | pubmed-4375073 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-43750732016-04-01 In Vivo Pancreatic β-Cell–Specific Expression of Antiaging Gene Klotho: A Novel Approach for Preserving β-Cells in Type 2 Diabetes Lin, Yi Sun, Zhongjie Diabetes Pharmacology and Therapeutics Protein expression of an antiaging gene, Klotho, was depleted in pancreatic islets in patients with type 2 diabetes mellitus (T2DM) and in db/db mice, an animal model of T2DM. The objective of this study was to investigate whether in vivo expression of Klotho would preserve pancreatic β-cell function in db/db mice. We report for the first time that β-cell–specific expression of Klotho attenuated the development of diabetes in db/db mice. β-Cell–specific expression of Klotho decreased hyperglycemia and enhanced glucose tolerance. The beneficial effects of Klotho were associated with significant improvements in T2DM-induced decreases in number of β-cells, insulin storage levels in pancreatic islets, and glucose-stimulated insulin secretion from pancreatic islets, which led to increased blood insulin levels in diabetic mice. In addition, β-cell–specific expression of Klotho decreased intracellular superoxide levels, oxidative damage, apoptosis, and DNAJC3 (a marker for endoplasmic reticulum stress) in pancreatic islets. Furthermore, β-cell–specific expression of Klotho increased expression levels of Pdx-1 (insulin transcription factor), PCNA (a marker of cell proliferation), and LC3 (a marker of autophagy) in pancreatic islets in db/db mice. These results reveal that β-cell–specific expression of Klotho improves β-cell function and attenuates the development of T2DM. Therefore, in vivo expression of Klotho may offer a novel strategy for protecting β-cells in T2DM. American Diabetes Association 2015-04 2014-11-05 /pmc/articles/PMC4375073/ /pubmed/25377875 http://dx.doi.org/10.2337/db14-0632 Text en © 2015 by the American Diabetes Association. 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. |
spellingShingle | Pharmacology and Therapeutics Lin, Yi Sun, Zhongjie In Vivo Pancreatic β-Cell–Specific Expression of Antiaging Gene Klotho: A Novel Approach for Preserving β-Cells in Type 2 Diabetes |
title | In Vivo Pancreatic β-Cell–Specific Expression of Antiaging Gene Klotho: A Novel Approach for Preserving β-Cells in Type 2 Diabetes |
title_full | In Vivo Pancreatic β-Cell–Specific Expression of Antiaging Gene Klotho: A Novel Approach for Preserving β-Cells in Type 2 Diabetes |
title_fullStr | In Vivo Pancreatic β-Cell–Specific Expression of Antiaging Gene Klotho: A Novel Approach for Preserving β-Cells in Type 2 Diabetes |
title_full_unstemmed | In Vivo Pancreatic β-Cell–Specific Expression of Antiaging Gene Klotho: A Novel Approach for Preserving β-Cells in Type 2 Diabetes |
title_short | In Vivo Pancreatic β-Cell–Specific Expression of Antiaging Gene Klotho: A Novel Approach for Preserving β-Cells in Type 2 Diabetes |
title_sort | in vivo pancreatic β-cell–specific expression of antiaging gene klotho: a novel approach for preserving β-cells in type 2 diabetes |
topic | Pharmacology and Therapeutics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375073/ https://www.ncbi.nlm.nih.gov/pubmed/25377875 http://dx.doi.org/10.2337/db14-0632 |
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