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Remission in models of type 1 diabetes by gene therapy using a single-chain insulin analogue

Authors
 Hyun Chul Lee  ;  Su-Jin Kim  ;  Kyung-Sup Kim  ;  Hang-Cheol Shin  ;  Ji-Won Yoon 
Citation
 Nature, Vol.23(408) : 483-488, 2000 
Journal Title
NATURE
ISSN
 0028-0836 
Issue Date
2000
MeSH
Animals ; Base Sequence ; Blood Glucose/metabolism ; Cloning, Molecular ; DNA, Complementary ; DNA, Recombinant/genetics ; DNA, Recombinant/metabolism ; Dependovirus/genetics ; Diabetes Mellitus, Experimental/therapy ; Diabetes Mellitus, Type 1/therapy* ; Escherichia coli ; Gene Expression ; Genetic Therapy* ; Genetic Vectors ; Glucose Tolerance Test ; Half-Life ; Hepatocytes/metabolism ; Insulin/analogs & derivatives ; Insulin/genetics* ; Insulin/secretion ; Liver/metabolism ; Male ; Mice ; Mice, Inbred NOD ; Molecular Sequence Data ; Plasmids ; Promoter Regions, Genetic ; Rats ; Rats, Sprague-Dawley
Abstract
A cure for diabetes has long been sought using several different approaches, including islet transplantation, regeneration of β cells and insulin gene therapy1. However, permanent remission of type 1 diabetes has not yet been satisfactorily achieved. The development of type 1 diabetes results from the almost total destruction of insulin-producing pancreatic β cells by autoimmune responses specific to β cells2,3,4,5,6. Standard insulin therapy may not maintain blood glucose concentrations within the relatively narrow range that occurs in the presence of normal pancreatic β cells7. We used a recombinant adeno-associated virus (rAAV) that expresses a single-chain insulin analogue (SIA), which possesses biologically active insulin activity without enzymatic conversion, under the control of hepatocyte-specific L-type pyruvate kinase (LPK) promoter, which regulates SIA expression in response to blood glucose levels. Here we show that SIA produced from the gene construct rAAV-LPK-SIA caused remission of diabetes in streptozotocin-induced diabetic rats and autoimmune diabetic mice for a prolonged time without any apparent side effects. This new SIA gene therapy may have potential therapeutic value for the cure of autoimmune diabetes in humans.
Full Text
http://www.nature.com/articles/35044106
DOI
10.1038/35044106
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Sup(김경섭) ORCID logo https://orcid.org/0000-0001-8483-8537
Lee, Hyun Chul(이현철)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/171809
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