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GLP-1-mediated gene therapy approaches for diabetes treatment

Published online by Cambridge University Press:  26 March 2014

Mukerrem Hale Tasyurek ,
Hasan Ali Altunbas ,
Halit Canatan ,
Thomas S. Griffith  and
Salih Sanlioglu
Mukerrem Hale Tasyurek
Affiliation:
Human Gene and Cell Therapy Center, Akdeniz University Hospitals, Antalya 07058, Turkey Department of Medical Biology and Genetics, Akdeniz University Faculty of Medicine, Antalya 07058, Turkey
Hasan Ali Altunbas
Affiliation:
Human Gene and Cell Therapy Center, Akdeniz University Hospitals, Antalya 07058, Turkey Department of Internal Medicine, Division of Endocrinology and Metabolism, Akdeniz University Faculty of Medicine, Antalya 07058, Turkey
Halit Canatan
Affiliation:
Genome and Stem Cell Research Center, Department of Medical Biology, Erciyes University Faculty of Medicine, Melikgazi, Kayseri 38039, Turkey
Thomas S. Griffith
Affiliation:
Department of Urology, University of Minnesota, Minneapolis, MN 55455, USA
Salih Sanlioglu*
Affiliation:
Human Gene and Cell Therapy Center, Akdeniz University Hospitals, Antalya 07058, Turkey Department of Medical Biology and Genetics, Akdeniz University Faculty of Medicine, Antalya 07058, Turkey
*
*Corresponding author: Professor Dr. Salih Sanlioglu VMD, PhD, Human Gene and Cell Therapy Center, Akdeniz University Hospitals and Clinics, B Block, 1st floor, Campus, Antalya 07058, Turkey. E-mail: sanlioglu@akdeniz.edu.tr
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Abstract

Glucagon-like peptide (GLP)-1 is an incretin hormone with several antidiabetic functions including stimulation of glucose-dependent insulin secretion, increase in insulin gene expression and beta-cell survival. Despite the initial technical difficulties and profound inefficiency of direct gene transfer into the pancreas that seriously restricted in vivo gene transfer experiments with GLP-1, recent exploitation of various routes of gene delivery and alternative means of gene transfer has permitted the detailed assessment of the therapeutic efficacy of GLP-1 in animal models of type 2 diabetes (T2DM). As a result, many clinical benefits of GLP-1 peptide/analogues observed in clinical trials involving induction of glucose tolerance, reduction of hyperglycaemia, suppression of appetite and food intake linked to weight loss have been replicated in animal models using gene therapy. Furthermore, GLP-1-centered gene therapy not only improved insulin sensitivity, but also reduced abdominal and/or hepatic fat associated with obesity-induced T2DM with drastic alterations in adipokine profiles in treated subjects. Thus, a comprehensive assessment of recent GLP-1-mediated gene therapy approaches with detailed analysis of current hurdles and resolutions, is discussed.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 16 , 2014 , e7
Copyright
Copyright © Cambridge University Press 2014 

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References

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Further reading, resources and contacts

Bryant, L.M. et al. (2013) Lessons learned from the clinical development and market authorization of Glybera. Human Gene Therapy Clinical Development 24, 55-64CrossRefGoogle ScholarPubMed
Tibaldi, J.M. (2014) Incorporating incretin-based therapies into clinical practice for patients with type 2 diabetes. Advances in Therapy doi:10.1007/s12325-014-0100-5CrossRefGoogle ScholarPubMed