The synthetic GLP-1 receptor agonist, exenatide, reduces intimal hyperplasia in insulin resistant rats

We studied the effect of a synthetic GLP-1 receptor agonist, exenatide, a drug approved for the treatment of type 2 diabetes, on the recovery from vascular injury in Zucker (non-diabetic) fatty rats. Exenatide 5.0 mu g/kg per day or saline was administered for seven days before, and 21 days after balloon catheter mediated carotid injury. A pair feeding experiment helped differentiate between the drug itself and the known effects of the drug on decreased food intake. Body weight and glucose (weekly), carotid artery I/M ratio, aortic protein eNOS and NF kappa B-p65 were measured. Body weight gain in exenatide rats was significantly lower (53 +/- 5 vs. 89 +/- 8 g) than controls. Blood glucose did not change significantly. The I/M ratio in the exenatide group was 0.2 +/- 0.1 vs. 0.9 +/- 0.1 in controls (p < 0.05). The expression of aortic eNOS was unchanged in exenatide treated rats and a small decrease seen in NF kappa B-p65 expression was not statistically significant. We conclude that exenatide attenuates intimal hyperplasia following balloon catheter induced vascular injury independently of glucose regulation and food intake. Our findings provide additional support for cardiovascular benefits of exenatide, especially in obese and pre-diabetic patients. Further research is needed to elucidate the mechanism underlying these effects.