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

Hyun Chul Lee (), Su-Jin Kim, Kyung-Sup Kim, Hang-Cheol Shin and Ji-Won Yoon
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Hyun Chul Lee: Division of Endocrinology, Department of Internal Medicine
Su-Jin Kim: Division of Endocrinology, Department of Internal Medicine
Kyung-Sup Kim: Yonsei University, College of Medicine
Hang-Cheol Shin: Division of Endocrinology, Department of Internal Medicine
Ji-Won Yoon: Division of Endocrinology, Department of Internal Medicine

Nature, 2000, vol. 408, issue 6811, 483-488

Abstract: 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.

Date: 2000
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DOI: 10.1038/35044106

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