Metformin does not enhance insulin-stimulated vasodilation in skeletal muscle resistance arteries of the OLETF rat.

OBJECTIVE: To test the hypothesis that chronic metformin treatment enhances insulin-induced vasodilation in skeletal muscle resistance arteries and arterioles. METHODS: We assessed the effect of metformin treatment (from 20 to 32 weeks of age) of obese Otsuka Long Evans Tokushima Fatty (OLETF) rats and lean LETO rats (300 mg/kg) on insulin-stimulated vasodilation in isolated skeletal muscle feed arteries and arterioles. RESULTS: Metformin treatment significantly lowered food intake, body weight, percent body fat, and HbA1c in OLETF rats. Metformin resulted in a ~30% reduction in insulin-induced vasodilation of soleus feed arteries (SFA) from OLETF rats. Inhibition of endothelin-1 (ET-1) signaling produced 20% dilation and eliminated the difference between metformin-treated and untreated OLETF rats in insulin-induced dilation of SFA. In contrast to the SFA, metformin did not alter insulin-stimulated vasodilation in gastrocnemius feed arteries (GFA), or second-order arterioles in the red (G2A-R) or white (G2A-W) portions of the gastrocnemius muscle of OLETF rats. Metformin had no effects on vasomotor responses of arteries from LETO. CONCLUSIONS: Although metformin exerts favorable effects on body composition and HbA1c, it does not enhance the vasodilatory responses to insulin in the skeletal muscle feed arteries or arterioles of the obese OLETF rat.