Targeting Uncoupling Protein-2 Improves Islet Graft Function

Preserving and enhancing the primary function of transplanted islets is not only crucial for improving the outcome of the islet transplantation, but is also important for reducing the islet mass required to achieve insulin independence. Uncoupling protein 2 (UCP2) is a member of the uncoupling prote...

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Main Authors: Dong Zhang, Miaoda Shen, Allison Mikita, Wensheng Zhang, Yun Liu, Quan Liu, Yifan Dai, Chenyu Zhang, Shusen Zheng, Xin Xiao Zheng M.D.
Format: Article
Language:English
Published: SAGE Publishing 2011-04-01
Series:Cell Transplantation
Online Access:https://doi.org/10.3727/096368910X522243
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spelling doaj-3b2ac20453064114b342d10495f49cbc2020-11-25T03:39:23ZengSAGE PublishingCell Transplantation0963-68971555-38922011-04-012010.3727/096368910X522243Targeting Uncoupling Protein-2 Improves Islet Graft FunctionDong Zhang0Miaoda Shen1Allison Mikita2Wensheng Zhang3Yun Liu4Quan Liu5Yifan Dai6Chenyu Zhang7Shusen Zheng8Xin Xiao Zheng M.D.9 Division of Plastic and Reconstructive Surgery, Thomas E. Starzl Transplantation Institute, Pittsburgh, PA, USA Division of Plastic and Reconstructive Surgery, Thomas E. Starzl Transplantation Institute, Pittsburgh, PA, USA Division of Plastic and Reconstructive Surgery, Thomas E. Starzl Transplantation Institute, Pittsburgh, PA, USA Division of Plastic and Reconstructive Surgery, Thomas E. Starzl Transplantation Institute, Pittsburgh, PA, USA Division of Plastic and Reconstructive Surgery, Thomas E. Starzl Transplantation Institute, Pittsburgh, PA, USA Division of Plastic and Reconstructive Surgery, Thomas E. Starzl Transplantation Institute, Pittsburgh, PA, USA Division of Plastic and Reconstructive Surgery, Thomas E. Starzl Transplantation Institute, Pittsburgh, PA, USA State Key Laboratory of Pharmaceutial Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China Division of Plastic and Reconstructive Surgery, Thomas E. Starzl Transplantation Institute, Pittsburgh, PA, USAPreserving and enhancing the primary function of transplanted islets is not only crucial for improving the outcome of the islet transplantation, but is also important for reducing the islet mass required to achieve insulin independence. Uncoupling protein 2 (UCP2) is a member of the uncoupling protein family, which is localized to the inner mitochondrial membrane and negatively regulates insulin secretion in the pancreatic β-cells. In this study, we assessed the importance of UCP2 in improving islet graft primary function by using UCP2 gene-knockout (UCP2-KO) mice in a syngeneic islet transplantation model. Islets were isolated from UCP2-KO or wild-type (WT) C57BL/6J mice. The effects of deficiency of UCP2 on islet transplantation and islet function were determined. Two hundred islets from UCP2-KO, but not from WT, donors were capable of completely restoring normoglycemia in 1 week in all syngeneic diabetic recipients. Islets harvested from UCP2-KO mice secreted onefold more insulin in GSIS assay than that from WT mice, and maintained normal GSIS after 72-h exposure to high glucose challenge. In addition, UCP2-KO islets expressed twohold higher Bcl-2 mRNA than that from WT islets, and were resistant to high glucose and proinflammatory cytokine induced death. Our study explored a potential mechanism that may explain the benefit of UCP2-KO islets in islet transplantation. Targeting UCP2 may provide a novel strategy to improve primary function of transplanted islets and reduce the number of islets required in transplantation.https://doi.org/10.3727/096368910X522243
collection DOAJ
language English
format Article
sources DOAJ
author Dong Zhang
Miaoda Shen
Allison Mikita
Wensheng Zhang
Yun Liu
Quan Liu
Yifan Dai
Chenyu Zhang
Shusen Zheng
Xin Xiao Zheng M.D.
spellingShingle Dong Zhang
Miaoda Shen
Allison Mikita
Wensheng Zhang
Yun Liu
Quan Liu
Yifan Dai
Chenyu Zhang
Shusen Zheng
Xin Xiao Zheng M.D.
Targeting Uncoupling Protein-2 Improves Islet Graft Function
Cell Transplantation
author_facet Dong Zhang
Miaoda Shen
Allison Mikita
Wensheng Zhang
Yun Liu
Quan Liu
Yifan Dai
Chenyu Zhang
Shusen Zheng
Xin Xiao Zheng M.D.
author_sort Dong Zhang
title Targeting Uncoupling Protein-2 Improves Islet Graft Function
title_short Targeting Uncoupling Protein-2 Improves Islet Graft Function
title_full Targeting Uncoupling Protein-2 Improves Islet Graft Function
title_fullStr Targeting Uncoupling Protein-2 Improves Islet Graft Function
title_full_unstemmed Targeting Uncoupling Protein-2 Improves Islet Graft Function
title_sort targeting uncoupling protein-2 improves islet graft function
publisher SAGE Publishing
series Cell Transplantation
issn 0963-6897
1555-3892
publishDate 2011-04-01
description Preserving and enhancing the primary function of transplanted islets is not only crucial for improving the outcome of the islet transplantation, but is also important for reducing the islet mass required to achieve insulin independence. Uncoupling protein 2 (UCP2) is a member of the uncoupling protein family, which is localized to the inner mitochondrial membrane and negatively regulates insulin secretion in the pancreatic β-cells. In this study, we assessed the importance of UCP2 in improving islet graft primary function by using UCP2 gene-knockout (UCP2-KO) mice in a syngeneic islet transplantation model. Islets were isolated from UCP2-KO or wild-type (WT) C57BL/6J mice. The effects of deficiency of UCP2 on islet transplantation and islet function were determined. Two hundred islets from UCP2-KO, but not from WT, donors were capable of completely restoring normoglycemia in 1 week in all syngeneic diabetic recipients. Islets harvested from UCP2-KO mice secreted onefold more insulin in GSIS assay than that from WT mice, and maintained normal GSIS after 72-h exposure to high glucose challenge. In addition, UCP2-KO islets expressed twohold higher Bcl-2 mRNA than that from WT islets, and were resistant to high glucose and proinflammatory cytokine induced death. Our study explored a potential mechanism that may explain the benefit of UCP2-KO islets in islet transplantation. Targeting UCP2 may provide a novel strategy to improve primary function of transplanted islets and reduce the number of islets required in transplantation.
url https://doi.org/10.3727/096368910X522243
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