Mice lacking endothelial nitric oxide synthase (eNOS-/-) exhibited hypertension, fasting hyperinsulinemia, hyperlipidemia, and a 40% lower insulin-stimulated glucose uptake than control mice.
Does eNOS deficiency cause insulin resistance, hyperlipidemia, and hypertension in mice?
eNOS deficiency in mice causes hypertension, hyperlipidemia, and insulin resistance, suggesting a mechanistic link between metabolic and cardiovascular diseases.
Effect estimate: 40% lower
BACKGROUND: Insulin resistance and arterial hypertension are related, but the underlying mechanism is unknown. Endothelial nitric oxide synthase (eNOS) is expressed in skeletal muscle, where it may govern metabolic processes, and in the vascular endothelium, where it regulates arterial pressure. METHODS AND RESULTS: To study the role of eNOS in the control of the metabolic action of insulin, we assessed insulin sensitivity in conscious mice with disruption of the gene encoding for eNOS. eNOS(-/-) mice were hypertensive and had fasting hyperinsulinemia, hyperlipidemia, and a 40% lower insulin-stimulated glucose uptake than control mice. Insulin resistance in eNOS(-/-) mice was related specifically to impaired NO synthesis, because in equally hypertensive 1-kidney/1-clip mice (a model of renovascular hypertension), insulin-stimulated glucose uptake was normal. CONCLUSIONS: These results indicate that eNOS is important for the control not only of arterial pressure but also of glucose and lipid homeostasis. A single gene defect, eNOS deficiency, may represent the link between metabolic and cardiovascular disease.
Duplain et al. (2001) studied Insulin resistance and arterial hypertension. eNOS gene disruption (eNOS-/-) vs. Control mice and 1-kidney/1-clip mice was evaluated on Insulin-stimulated glucose uptake (40% lower). Mice lacking endothelial nitric oxide synthase (eNOS-/-) exhibited hypertension, fasting hyperinsulinemia, hyperlipidemia, and a 40% lower insulin-stimulated glucose uptake than control mice.