title: GLP-1-mediated gene therapy approaches for diabetes treatment.
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.
authors.affiliation: Human Gene and Cell Therapy Center, Akdeniz University Hospitals, Antalya 07058, Turkey.
authors.forename: Mukerrem Hale
authors.initials: MH
authors.lastname: Tasyurek
authors.affiliation: Human Gene and Cell Therapy Center, Akdeniz University Hospitals, Antalya 07058, Turkey.
authors.forename: Hasan Ali
authors.initials: HA
authors.lastname: Altunbas
authors.affiliation: Genome and Stem Cell Research Center, Department of Medical Biology, Erciyes University Faculty of Medicine, Melikgazi, Kayseri 38039, Turkey.
authors.forename: Halit
authors.initials: H
authors.lastname: Canatan
authors.affiliation: Department of Urology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Griffith
authors.affiliation: Human Gene and Cell Therapy Center, Akdeniz University Hospitals, Antalya 07058, Turkey.
authors.forename: Salih
authors.initials: S
authors.lastname: Sanlioglu
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000229:Dependovirus / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000628:therapy*; D015316:Genetic Therapy; D005822:Genetic Vectors; D052216:Glucagon-Like Peptide 1 / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D016662:Virus Integration
chemical_list: D052216:Glucagon-Like Peptide 1