Restrictive diet during pregnancy‐induced vascular dysfunction and hypertension in mice is associated with insulin resistance

Abstract

In mice, restrictive diet pregnancy (RDP), a model mimicking preeclampsia in humans, induces vascular dysfunction in the offspring that is related to 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 offspring of RDP mice are insulin‐resistant.We, therefore, assessed insulin sensitivity (euglycemic‐hyperinsulinemic clamp studies) in offspring of RDP 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 offspring of RDP than in control mice, as evidenced by a markedly smaller glucose infusion rate to maintain euglycemia (77.4±10.7 vs. 96.7±12.2, P<.001) in offspring of RDP than in control mice. Insulin resistance was not related to an intrinsic defect of skeletal muscle because muscle glucose uptake was comparable in the 2 groups. 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. Preeclampsia‐induced vascular dysfunction has also been found in humans. We speculate that preeclampsia represents a novel risk factor facilitating diet‐induced insulin resistance in humans.Grant support: Swiss National Science Foundation and Swiss Society of Hypertension