Objective        To construct and identity a self complementary double-stranded recombinant adeno-associated virus vector (scAAV) to secrete Exendin-4 (Ex-4). The transduction efficiency of the recombinant scAAV-Ex-4 was evaluated and its efficacy in tre

atment of diabetic rats was observed.       Methods        The shuttle vector pSSHG-CMV inserted with Ex-4 gene was constructed by genetic engineering method. The scAAV-Ex-4 vector was co-transferred into HEK-293 cells. Ex-4 level in the supernatants from transfected NIH3T3 cells was determined by an enzyme immunoassay kit. The rat model of type 2 diabetes (T2DM) was successfully induced by streptozotocin in twenty six-week-old Sprague-Dawley (SD) male rats (160-180 g). The recombinant scAAV was injected into the salivary gland of T2DM model rats. The levels of blood glucose and insulin of the rats were assessed.       Results        The recombinant scAAV-Ex-4 was successfully constructed and packaged with a high titer of virus (2.5×10

11

pfu/L). The Ex-4 concentration of the supernatants from transfected cells could be 4.53 ng/mL. The mean levels of blood glucose and insulin at 2

4 and 8 weeks were significantly different between scAAV treatment groups and control groups (

P

<

0.05). The mean level of blood glucose in scAAV treated rats was lower than that in the control group (639.17±27.89 

vs

396.00±34.00

657.02±39.87 

vs

315.62±42.56

215.6±24.7 

vs

458.6±19.7 mg/dL)

but the mean level of insulin was higher (156.8±24.5 

vs

535.9±35.6

236.5±12.3

vs

495.3±18.6

620.43±46.90

vs

381.56±21.78 pg/mL).       Conclusion       The scAAV-Ex-4 can improve glycemic control and increase insulinotropic effect in T2DM model rats.