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Published on: June 25, 2012
Double-strand adeno-associated virus-mediated exendin-4 expression in salivary glands is efficient in a diabetic rat
Junhong Wang1, Feng Wang2, Jing Xu1
1Department of Endocrine, The Second Hospital, Medical College of Xi'an Jiaotong University, Xi'an 710004, China.
Aim:
Exendin-4 (Ex-4) is an agonist of the glucagon-like peptide 1 (GLP-1) receptor, approved for the treatment of type 2 diabetes (T2DM). Several strategies have been tried to develop stable and efficacious Ex-4 expression systems. The purpose of the current study was to determine whether double-stranded adeno-associated virus (dsAAV)-mediated in vivo expression of exendin-4 in salivary glands (SG), improves pathology in the Sprague-Dawley (SD) rat model of diabetes mellitus (DM).
Methods:
The effects of Ex-4 expression by recombinant dsAAV-NT4-Ex-4 were evaluated in vitro compared with a single-strand (ss) AAV. The dsAAV was delivered into SGs and the blood glucose and insulin levels were assessed in a rat model of DM.
Results:
DsAAV-NT4-Ex-4 virus induces significant exendin-4 expression in vitro. Furthermore, Ex-4 expressed from dsAAV virus in SGs enhances insulins secretion in vivo and significantly controls the onset of hyperglycemia in rat model of DM.
Conclusions:
Results suggest that sustained secretion of Ex-4 following dsAAV-mediated gene therapy is feasible. SGs appear to be promising targets with potential clinical applicability for the treatment of DM. This represents the example of a successful use of Ex-4 for diabetes therapy, providing support for direct AAV-mediated in vivo as an easy, safe and efficient therapeutic strategy.
