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糖尿病胰岛素替代的细胞工程和基因治疗策略

Cellular engineering and gene therapy strategies for insulin replacement in diabetes.

作者信息

Newgard C B

机构信息

Gillford Laboratories for Diabetes Research, University of Texas Southwestern Medical Center, Dallas 75235.

出版信息

Diabetes. 1994 Mar;43(3):341-50. doi: 10.2337/diab.43.3.341.

DOI:10.2337/diab.43.3.341
PMID:8314006
Abstract

In diabetes, insulin secretion is either completely absent (insulin-dependent diabetes mellitus [IDDM]) or inappropriately regulated (non-insulin-dependent diabetes mellitus [NIDDM]). In recent years, new insights into the molecular and biochemical mechanism(s) of fuel-mediated insulin release coupled with advances in gene transfer technology have led to the investigation of molecular strategies for replacement of normal insulin delivery function. Such initiatives have included attempts to engineer glucose-stimulated insulin secretion in cell lines that might serve as surrogates for islets in IDDM. The development of DNA virus gene transfer systems of remarkable efficiency also has suggested ways in which the beta-cell dysfunction of NIDDM might ultimately be repaired by gene therapy. The emerging work in these areas and implications for the future are summarized in this perspective.

摘要

在糖尿病中,胰岛素分泌要么完全缺失(胰岛素依赖型糖尿病[IDDM]),要么调节不当(非胰岛素依赖型糖尿病[NIDDM])。近年来,对燃料介导的胰岛素释放的分子和生化机制的新见解,再加上基因转移技术的进步,引发了对替代正常胰岛素递送功能的分子策略的研究。这些举措包括尝试在细胞系中设计葡萄糖刺激的胰岛素分泌,这些细胞系可作为IDDM中胰岛的替代物。高效DNA病毒基因转移系统的发展也提出了通过基因治疗最终修复NIDDM中β细胞功能障碍的方法。本文将概述这些领域的新进展及其对未来的影响。

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Cellular engineering and gene therapy strategies for insulin replacement in diabetes.糖尿病胰岛素替代的细胞工程和基因治疗策略
Diabetes. 1994 Mar;43(3):341-50. doi: 10.2337/diab.43.3.341.
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Recent progress in the molecular genetic aspects of non-insulin-dependent diabetes mellitus.非胰岛素依赖型糖尿病分子遗传学方面的最新进展。
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Beta cell dysfunction in non-insulin-dependent diabetes mellitus.非胰岛素依赖型糖尿病中的β细胞功能障碍。
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Gene therapy for diabetes mellitus.糖尿病的基因治疗
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Engineering of a glucose-responsive surrogate cell for insulin replacement therapy of experimental insulin-dependent diabetes.构建用于实验性胰岛素依赖型糖尿病胰岛素替代治疗的葡萄糖反应性替代细胞。
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Adeno-associated virus vector mediated gene transfer to pancreatic beta cells.腺相关病毒载体介导的基因转移至胰腺β细胞。
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Gene and cell therapies for diabetes mellitus: strategies and clinical potential.糖尿病的基因和细胞疗法:策略与临床潜力
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Early diabetes and abnormal postnatal pancreatic islet development in mice lacking Glut-2.缺乏葡萄糖转运蛋白2(Glut-2)的小鼠出现早期糖尿病及出生后胰岛发育异常。
Nat Genet. 1997 Nov;17(3):327-30. doi: 10.1038/ng1197-327.

引用本文的文献

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Reversal of diabetes following transplantation of an insulin-secreting human liver cell line: Melligen cells.胰岛细胞移植逆转糖尿病:Melligen 细胞。
Mol Ther Methods Clin Dev. 2015 Apr 8;2:15011. doi: 10.1038/mtm.2015.11. eCollection 2015.
2
Glucagon secretion and signaling in the development of diabetes.糖尿病发生发展过程中的胰高血糖素分泌与信号传导
Front Physiol. 2012 Sep 4;3:349. doi: 10.3389/fphys.2012.00349. eCollection 2012.
3
Combinatorial insulin secretion dynamics of recombinant hepatic and enteroendocrine cells.
重组肝和肠内分泌细胞的组合胰岛素分泌动力学。
Biotechnol Bioeng. 2012 Apr;109(4):1074-82. doi: 10.1002/bit.24373. Epub 2011 Nov 21.
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The role of incretins in glucose homeostasis and diabetes treatment.肠促胰岛素在葡萄糖稳态和糖尿病治疗中的作用。
Pharmacol Rev. 2008 Dec;60(4):470-512. doi: 10.1124/pr.108.000604. Epub 2008 Dec 12.
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Insulin gene transfer enhances the function of human islet grafts.胰岛素基因转移增强人胰岛移植的功能。
Diabetologia. 2003 Mar;46(3):386-93. doi: 10.1007/s00125-003-1038-3. Epub 2003 Mar 7.
6
Glucose-modulated transgene expression via recombinant adeno-associated virus.通过重组腺相关病毒实现葡萄糖调节的转基因表达。
Pharm Res. 2002 Jul;19(7):968-75. doi: 10.1023/a:1016410221197.
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Glucose-responsive gene delivery in pancreatic Islet cells via recombinant adeno-associated viral vectors.通过重组腺相关病毒载体在胰岛细胞中进行葡萄糖反应性基因递送。
Pharm Res. 2000 Sep;17(9):1056-61. doi: 10.1023/a:1026445426982.
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The glucose sensor protein glucokinase is expressed in glucagon-producing alpha-cells.葡萄糖传感器蛋白葡萄糖激酶在产生胰高血糖素的α细胞中表达。
Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7036-41. doi: 10.1073/pnas.93.14.7036.
9
[Insulin producing cells as therapy in diabetes mellitus].[胰岛素产生细胞作为糖尿病的治疗方法]
Naturwissenschaften. 1996 Jan;83(1):1-5.