We recently found that assisted reproductive technologies (ART) induce vascular dysfunction in mice and humans that is related to epigenetic mechanisms involving decreased vascular nitric oxide (NO) bioavailability. There is abundant evidence that NO plays an important role in the regulation of insulin sensitivity in animals and humans. We speculated that ART mice are insulin‐resistant.

To test this hypothesis, we assessed insulin sensitivity (intraperitoneal insulin tolerance test, 0.5 U/kg) in ART and control mice fed with high‐fat diet (HFD) for 8 wks.

The main new finding was that HFD induced much more severe insulin resistance in ART than in control mice, as evidenced by a markedly smaller insulin‐induced decrease of the plasma glucose level (measured every 15 min during 1 h after insulin injection) in ART than in control mice (ANOVA<0.0001; AUC: 4400±204 vs. 3625±131, P=0.005). We demonstrate for the very first time that ART causes insulin resistance in mice. In analogy to other NO‐deficient states, this problem is probably related to vascular dysfunction resulting in impaired insulin stimulation of blood flow and substrate delivery to skeletal muscle tissue. ART‐induced vascular dysfunction has also been found in humans. We speculate that ART represents a novel risk factor facilitating diet‐induced insulin resistance in humans.