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.
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.
Authors: Feng Li; John R Hagaman; Hyung-Suk Kim; Nobuyo Maeda; J Charles Jennette; James E Faber; S Ananth Karumanchi; Oliver Smithies; Nobuyuki Takahashi Journal: J Am Soc Nephrol Date: 2012-01-26 Impact factor: 10.121
Authors: Mattias Carlström; Filip J Larsen; Thomas Nyström; Michael Hezel; Sara Borniquel; Eddie Weitzberg; Jon O Lundberg Journal: Proc Natl Acad Sci U S A Date: 2010-09-27 Impact factor: 11.205
Authors: Hyun-Ju Jang; Hae-Suk Kim; Daniel H Hwang; Michael J Quon; Jeong-a Kim Journal: Am J Physiol Endocrinol Metab Date: 2013-03-26 Impact factor: 4.310