| Title : Adenoviral vector-mediated glucagon-like peptide 1 gene therapy improves glucose homeostasis in Zucker diabetic fatty rats - Lee_2008_J.Gene.Med_10_260 |
| Author(s) : Lee Y , Kwon MK , Kang ES , Park YM , Choi SH , Ahn CW , Kim KS , Park CW , Cha BS , Kim SW , Sung JK , Lee EJ , Lee HC |
| Ref : J Gene Med , 10 :260 , 2008 |
| Abstract : BACKGROUND: Glucagon-like peptide-1 (GLP-1) is a gut-derived incretin hormone that plays an important role in glucose homeostasis. Its functions include glucose-stimulated insulin secretion, suppression of glucagon secretion, deceleration of gastric emptying, and reduction in appetite and food intake. Despite the numerous antidiabetic properties of GLP-1, its therapeutic potential is limited by its short biological half-life due to rapid enzymatic degradation by dipeptidyl peptidase IV. The present study aimed to demonstrate the therapeutic effects of constitutively expressed GLP-1 in an overt type 2 diabetic animal model using an adenoviral vector system. METHODS: A novel plasmid (pAAV-ILGLP-1) and recombinant adenoviral vector (Ad-ILGLP-1) were constructed with the cytomegalovirus promoter and insulin leader sequence followed by GLP-1(7-37) cDNA. RESULTS: The results of an enzyme-linked immunosorbent assay showed significantly elevated levels of GLP-1(7-37) secreted by human embryonic kidney cells transfected with the construct containing the leader sequence. A single intravenous administration of Ad-ILGLP-1 into 12-week-old Zucker diabetic fatty (ZDF) rats, which have overt type 2 diabetes mellitus (T2DM), achieved near normoglycemia for 3 weeks and improved utilization of blood glucose in glucose tolerance tests. Circulating plasma levels of GLP-1 increased in GLP-1-treated ZDF rats, but diminished 21 days after treatment. When compared with controls, Ad-ILGLP-1-treated ZDF rats had a lower homeostasis model assessment for insulin resistance score indicating amelioration in insulin resistance. Immunohistochemical staining showed that cells expressing GLP-1 were found in the livers of GLP-1-treated ZDF rats. CONCLUSIONS: These data suggest that GLP-1 gene therapy can improve glucose homeostasis in fully developed diabetic animal models and may be a promising treatment modality for T2DM in humans. |
| ESTHER : Lee_2008_J.Gene.Med_10_260 |
| PubMedSearch : Lee_2008_J.Gene.Med_10_260 |
| PubMedID: 18085721 |
Lee Y, Kwon MK, Kang ES, Park YM, Choi SH, Ahn CW, Kim KS, Park CW, Cha BS, Kim SW, Sung JK, Lee EJ, Lee HC (2008)
Adenoviral vector-mediated glucagon-like peptide 1 gene therapy improves glucose homeostasis in Zucker diabetic fatty rats
J Gene Med
10 :260
Lee Y, Kwon MK, Kang ES, Park YM, Choi SH, Ahn CW, Kim KS, Park CW, Cha BS, Kim SW, Sung JK, Lee EJ, Lee HC (2008)
J Gene Med
10 :260