Nitric oxide and vascular insulin resistance

  title={Nitric oxide and vascular insulin resistance},
  author={Guoyao Wu and Cynthia Meininger},
Obesity and type‐II diabetes are growing major health issues worldwide. They are the leading risk factors for vascular insulin resistance, which plays an important role in the pathogenesis of cardiovascular disease, the leading cause of death in developed nations. Recent studies have shown that reduced synthesis of nitric oxide (NO; a major vasodilator) from L‐arginine in endothelial cells is a major factor contributing to the impaired action of insulin in the vasculature of obese and diabetic… 

l-Leucine and NO-mediated cardiovascular function

It is proposed that reducing circulating levels of l-leucine or endothelial GFAT activity may provide a potentially novel strategy for preventing and/or treating cardiovascular disease in obese and diabetic subjects.

Uric acid induces endothelial dysfunction by vascular insulin resistance associated with the impairment of nitric oxide synthesis

Taking together, uric acid induced endothelial dysfunction by contributing to vascular insulin resistance in terms of insulin‐induced NO production, potentially leading to the development of hypertension.

Association between insulin resistance and the development of cardiovascular disease

It can be concluded that insulin resistance in the myocardium generates damage by at least three different mechanisms: (1) signal transduction alteration, (2) impaired regulation of substrate metabolism, and (3) altered delivery of substrates to theMyocardium.

Nitric oxide and energy metabolism in mammals

Modulation of NO‐mediated pathways through dietary supplementation with L‐arginine or its precursor L‐citrulline may provide an effective, practical strategy to prevent and treat metabolic syndrome, including obesity, diabetes, and dyslipidemia in mammals, including humans.

Anti-obesity and anti-diabetic effects of nitrate and nitrite.

Renal endothelial dysfunction in diabetic nephropathy.

Both pharmacological approaches and potential regenerative therapies hold promise for restoration of impaired endothelial cells in diabetic nephropathy.

Regulation of nitric oxide production in health and disease

Future research is needed to expand the understanding of the regulation and adequate measurement of nitric oxide production at the organ level and by the different Nitric oxide synthase isoforms, also in relation to clinical nutrition.

The nitrate-nitrite-nitric oxide pathway: Its role in human exercise physiology

There is evidence that the muscle ATP turnover at a fixed work rate is reduced and the mitochondrial P/O ratio is increased following NO3 − supplementation, which offers important insights into the physiological bases for the reduced during exercise.

A Mitochondrial Approach to Cardiovascular Risk and Disease.

Regular physical activity has been shown to improve mitochondrial parameters and myocardial tolerance to ischemia-reperfusion (IR) and several approaches that act by improving mitochondrial function in the heart, contributing to decrease some of the risk factors associated to CVDs.



Arginine nutrition and cardiovascular function.

Dietary Arg supplementation may represent a potentially novel nutritional strategy for preventing and treating cardiovascular disease.

Effect of Endothelium-Specific Insulin Resistance on Endothelial Function In Vivo

Selective endothelial insulin resistance is sufficient to induce a reduction in NO bioavailability and endothelial dysfunction that is secondary to increased generation of reactive oxygen species, independent of a significant metabolic phenotype.

Cardiovascular actions of insulin.

Molecular mechanisms underlying cardiovascular actions of insulin, the reciprocal relationships between insulin resistance and endothelial dysfunction, and implications for developing beneficial therapeutic strategies that simultaneously target metabolic and cardiovascular diseases are discussed.

Impaired arginine metabolism and NO synthesis in coronary endothelial cells of the spontaneously diabetic BB rat.

Arginine metabolism via nitric oxide (NO) synthase and other pathways was studied in coronary endothelial cells (EC) from the spontaneously diabetic BB rat, an animal model of human type I diabetes

Vascular function, insulin resistance and fatty acids

Raised non-esterified fatty acids impair insulin's effect on glucose uptake in skeletal muscle and the vascular endothelium and thus could have detrimental effects on the vasculature, leading to premature cardiovascular disease.

Regulation of nitric oxide synthesis by dietary factors.

The discovery of NO synthesis has unified traditionally diverse research areas in nutrition, physiology, immunology, pathology, and neuroscience, and it is necessary to investigate the interactions of dietary factors on NO synthesis and to define the underlying molecular mechanisms.

Impaired nitric oxide production in coronary endothelial cells of the spontaneously diabetic BB rat is due to tetrahydrobiopterin deficiency.

Endothelial cells from diabetic BioBreeding rats have an impaired ability to produce NO because of a deficiency in tetrahydrobiopterin (BH(4), a cofactor necessary for enzyme activity in de novo biosynthesis of GTP-cyclohydrolase I, and increasing BH( 4) levels with sepiapterin increased NO production.

Tetrahydrobiopterin increases insulin sensitivity in patients with type 2 diabetes and coronary heart disease.

BH(4) significantly increases insulin sensitivity in type 2 diabetic patients without any discernible improvement in endothelial function and does not affect the relative changes in brachial artery diameter from baseline FMD.

Tetrahydrobiopterin-dependent preservation of nitric oxide-mediated endothelial function in diabetes by targeted transgenic GTP-cyclohydrolase I overexpression.

Findings indicate that BH4 is an important mediator of eNOS regulation in diabetes and is a rational therapeutic target to restore NO-mediated endothelium-dependent vasodilatation in Diabetes and other vascular disease states.