Insulin resistance, hyperlipidemia, and hypertension in mice lacking endothelial nitric oxide synthase.
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.


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
H
H
Department of Internal Medicine, Division of Hypertension and Vascular Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Burcelin
R
R
Sartori
C
C
Cook
S
S
Egli
M
M
Lepori
M
M
Vollenweider
P
P
Pedrazzini
T
T
Nicod
P
P
Thorens
B
B
Scherrer
U
U
D000818:Animals; D001158:Arteries; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism / Q000493:pharmacokinetics; D015309:Glucose Clamp Technique; D006614:Hindlimb / Q000098:blood supply; D006720:Homozygote; D006946:Hyperinsulinism / Q000150:complications / Q000235:genetics; D006949:Hyperlipidemias / Q000150:complications / Q000235:genetics*; D006973:Hypertension / Q000150:complications / Q000235:genetics*; D006978:Hypertension, Renovascular / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism; D009566:Nitrates / Q000097:blood; D019001:Nitric Oxide Synthase / Q000172:deficiency* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009573:Nitrites / Q000097:blood
D001786:Blood Glucose; D007328:Insulin; D009566:Nitrates; D009573:Nitrites; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D005947:Glucose