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Insulin gene therapy from design to beta cell generation

Published online by Cambridge University Press:  15 October 2012

Ahter D. Sanlioglu ,
Hasan Ali Altunbas ,
Mustafa Kemal Balci ,
Thomas S. Griffith  and
Salih Sanlioglu
Ahter D. Sanlioglu
Affiliation:
Human Gene and Cell Therapy Center, Antalya, Turkey Department of Medical Biology and Genetics, Antalya, Turkey
Hasan Ali Altunbas
Affiliation:
Human Gene and Cell Therapy Center, Antalya, Turkey Department of Internal Medicine, Division of Endocrinology and Metabolism, Akdeniz University Faculty of Medicine, Antalya, Turkey
Mustafa Kemal Balci
Affiliation:
Human Gene and Cell Therapy Center, Antalya, Turkey Department of Internal Medicine, Division of Endocrinology and Metabolism, Akdeniz University Faculty of Medicine, Antalya, Turkey
Thomas S. Griffith
Affiliation:
Department of Urology, University of Minnesota, Minneapolis, MN, USA
Salih Sanlioglu*
Affiliation:
Human Gene and Cell Therapy Center, Antalya, Turkey Department of Medical Biology and Genetics, Antalya, Turkey
*
*Corresponding author: Salih Sanlioglu VMD, Human Gene and Cell Therapy Center, Akdeniz University Hospitals and Clinics, B Block, 1st Floor, Campus, Antalya, Turkey. Email: sanlioglu@akdeniz.edu.tr
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Abstract

Despite the fact that insulin injection can protect diabetic patients from developing diabetes-related complications, recent meta-analyses indicate that rapid and long-acting insulin analogues only provide a limited benefit compared with conventional insulin regarding glycemic control. As insulin deficiency is the main sequel of type-1 diabetes (T1D), transfer of the insulin gene-by-gene therapy is becoming an attractive treatment modality even though T1D is not caused by a single genetic defect. In contrast to human insulin and insulin analogues, insulin gene therapy targets to supplement patients not only with insulin but also with C-peptide. So far, insulin gene therapy has had limited success because of delayed and/or transient gene expression. Sustained insulin gene expression is now feasible using current gene-therapy vectors providing patients with basal insulin coverage, but management of postprandial hyperglycaemia is still difficult to accomplish because of the inability to properly control insulin secretion. Enteroendocrine cells of the gastrointestinal track (K cells and L cells) may be ideal targets for insulin gene therapy, but cell-targeting difficulties have limited practical implementation of insulin gene therapy for diabetes treatment. Therefore, recent gene transfer technologies developed to generate authentic beta cells through transdifferentiation are also highlighted in this review.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 14 , March 2012 , e18
Copyright
Copyright © Cambridge University Press 2012

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Further reading, resources and contacts

Roth, J et al. (2012) Insulin's discovery: new insights on its ninetieth birthday. Diabetes Metabolism Research and Reviews 28, 293-304CrossRefGoogle ScholarPubMed
US National Diabetes Fact Sheet 2011 can be found at http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf website. The data is generated from Centers for Disease Control and Prevention (CDC), the Indian Health Service's (IHS) National Patient Information Reporting System (NPIRS), the US. Renal Data System of the National Institutes of Health (NIH), the US. Census Bureau, and published studies.Google Scholar