Insulin resistance, hyperlipidemia, and hypertension in mice lacking endothelial nitric oxide synthase
Abstract
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.
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Deletion of NOS3 in mice causes insulin resistance, hyperlipidemia, and hypertension.
“In mice, it has been reported that deletion of NOS3 causes insulin resistance, hyperlipidemia, and hypertension [326].”
From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [326]
Rats and mice made insulin-resistant by high fat intake have such severe impairment of microvascular blood flow that the delivery of glucose to skeletal muscle limits insulin-stimulated glucose uptake during an insulin clamp.
“rats and mice made insulin-resistant by high fat intake have such severe impairment of microvascular blood flow that the delivery of glucose to skeletal muscle limits insulin-stimulated glucose uptake during an insulin clamp.”
From The Vasculature in Prediabetes (2018) · cites this paper as [148]
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References 27 · Cited by 533
Research works printed but not linked: 1
- Sartori C, Scherrer U. Insulin as a vasoactive hormone: at the crossroad of metabolic and cardiovascular regulation. J Hypertens. 1999;17: 1517-1525.
- Authors
- Duplain, H., Burcelin, R., Sartori, C., Cook, S., Egli, M., Lepori, M., Vollenweider, P., Pedrazzini, T., Nicod, P., Thorens, B., & Scherrer, U.
- Affiliations
- From the Department of Internal Medicine and the Botnar Center for Clinical Research (H.D., C.S., S.C., M.E., M.L., P.V., P.N., U.S.) and the Division of Hypertension and Vascular Medicine (T.P.), Centre Hospitalier Universitaire Vaudois, and the Institute of Pharmacology and Toxicology, University of Lausanne (R.B., B.T.), Lausanne, Switzerland.
- Centre Hospitalier Universitaire Vaudois (CH)
- Venue
- Circulation
- Published
- 2001-07-17
- Volume
- 104
- Issue
- 3
- Pages
- 342-345
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W1928175618
- Cited by
- 533
- References
- 27
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 12 · 2023: 7 · 2022: 19 · 2021: 18 · 2020: 16 · 2019: 13 · 2018: 16 · 2017: 23 · 2016: 17 · 2015: 29 · 2014: 31 · 2013: 32 · 2012: 40
- FWCI
- 11.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- International Olympic Committee
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- endothelial nitric oxide synthase, insulin resistance, hyperlipidemia, hypertension, insulin-stimulated glucose uptake, nitric oxide production, eNOS knockout mice, renovascular hypertension, glucose and lipid homeostasis
- MeSH terms
- Animals, Arteries, Blood Flow Velocity, Blood Glucose, Body Weight, Disease Models, Animal, Glucose, Hindlimb, Homozygote, Hyperinsulinism, Hyperlipidemias, Hypertension, Hypertension, Renovascular, Insulin, Insulin Resistance, Nitrates, Nitrites, Glucose Clamp Technique, Mice, Knockout, Muscle, Skeletal, Nitric Oxide Synthase, Mice, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type III, In Vitro Techniques
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