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Nitric Oxide And Vascular Insulin Resistance

G. Wu, C. Meininger
Published 2009 · Medicine, Biology

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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 subjects. The decreased NO generation results from a deficiency of (6R)‐5,6,7,8‐tetrahydrobiopterin [BH4; an essential cofactor for NO synthase (NOS)], as well as increased generation of glucosamine (an inhibitor of the pentose cycle for the production of NADPH, another cofactor for NOS) from glucose and L‐glutamine. Accordingly, endothelial dysfunction can be prevented by (1) enhancement of BH4 synthesis through supplementation of its precursor (sepiapterin) via the salvage pathway; (2) transfer of the gene for GTP cyclohydrolase‐I (the first and key regulatory enzyme for de novo synthesis of BH4); or (3) dietary supplementation of L‐arginine (which stimulates GTP cyclohydrolase‐I expression and inhibits hexosamine production). Modulation of the arginine–NO pathway by BH4 and arginine is beneficial for ameliorating vascular insulin resistance in obesity and diabetes. © 2009 International Union of Biochemistry and Molecular Biology, Inc.
This paper references
10.1007/s00726-007-0502-7
In silico analysis of arginine catabolism as a source of nitric oxide or polyamines in endothelial cells
R. Montañez (2007)
10.1093/JN/134.3.600
Dietary L-arginine supplementation enhances endothelial nitric oxide synthesis in streptozotocin-induced diabetic rats.
R. Kohli (2004)
10.2337/DIABETES.49.5.684
Mice with gene disruption of both endothelial and neuronal nitric oxide synthase exhibit insulin resistance.
R. Shankar (2000)
10.1016/J.JNUTBIO.2007.06.011
Oxidative stress-induced risk factors associated with the metabolic syndrome: a unifying hypothesis.
I. Grattagliano (2008)
10.1007/s00726-008-0192-9
Metabolomic analysis of the response of growing pigs to dietary l-arginine supplementation
Qinghua He (2008)
10.1172/JCI118349
Glucosamine induces insulin resistance in vivo by affecting GLUT 4 translocation in skeletal muscle. Implications for glucose toxicity.
A. Baron (1995)
10.1007/s00125-002-0800-2
Vascular function, insulin resistance and fatty acids
H. Steinberg (2002)
10.1172/JCI17786
Tetrahydrobiopterin-dependent preservation of nitric oxide-mediated endothelial function in diabetes by targeted transgenic GTP-cyclohydrolase I overexpression.
N. Alp (2003)
10.1210/ER.2007-0006
Cardiovascular actions of insulin.
R. Muniyappa (2007)
10.1172/JCI117433
Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release.
H. Steinberg (1994)
10.1152/AJPENDO.00046.2004
Tetrahydrobiopterin increases insulin sensitivity in patients with type 2 diabetes and coronary heart disease.
T. Nyström (2004)
10.1146/ANNUREV.NUTR.22.110901.145329
Regulation of nitric oxide synthesis by dietary factors.
G. Wu (2002)
10.1007/s00726-007-0001-x
A new selective pre-column ninhydrin-based derivatization for a RP-HPLC determination of plasma asymmetric dimethyl-l-arginine (ADMA) by fluorescence detection
S. Sotgia (2007)
10.1006/abbi.1996.0543
Human endothelial nitric oxide synthase: expression in Escherichia coli, coexpression with calmodulin, and characterization.
I. Rodríguez-Crespo (1996)
10.1161/01.CIR.0000066909.13953.F1
Critical Role of l-Arginine in Endothelial Cell Survival During Oxidative Stress
C. Suschek (2003)
10.1096/fj.00-0893fje
Glucose‐6‐phosphate dehydrogenase deficiency promotes endothelial oxidant stress and decreases endothelial nitric oxide bioavailability
J. Leopold (2001)
10.1074/jbc.M603606200
Evidence for the Pathophysiological Role of Endogenous Methylarginines in Regulation of Endothelial NO Production and Vascular Function*
A. Cardounel (2007)
10.1016/J.JNUTBIO.2005.12.001
Regulatory role for the arginine-nitric oxide pathway in metabolism of energy substrates.
W. Jobgen (2006)
10.1159/000068938
Lack of Nitric Oxide Mediation of Flow-Dependent Arteriolar Dilation in Type I Diabetes Is Restored by Sepiapterin
Zsolt Bagi (2003)
10.1093/JN/137.12.2680
Dietary supplementation with watermelon pomace juice enhances arginine availability and ameliorates the metabolic syndrome in Zucker diabetic fatty rats.
G. Wu (2007)
10.1042/0264-6021:3530245
Glutamine metabolism to glucosamine is necessary for glutamine inhibition of endothelial nitric oxide synthesis.
G. Wu (2001)
10.1172/JCI118876
Overexpression of glutamine:fructose-6-phosphate amidotransferase in transgenic mice leads to insulin resistance.
L. Hebert (1996)
10.2337/diab.41.9.1076
Impaired Insulin-Mediated Skeletal Muscle Blood Flow in Patients With NIDDM
M. Laakso (1992)
10.2337/db07-1111
Effect of Endothelium-Specific Insulin Resistance on Endothelial Function In Vivo
E. Duncan (2008)
10.1046/j.1365-2362.1997.1730718.x
Effects of low‐dose l‐arginine on insulin‐mediated vasodilatation and insulin sensitivity
T. Wascher (1997)
10.1007/s00726-008-0052-7
Proline metabolism in the conceptus: implications for fetal growth and development
G. Wu (2008)
10.3132/dvdr.2008.027
Metformin therapy and clinical uses
J. Scarpello (2008)
10.1016/J.JNUTBIO.2007.06.006
Role of adipocytokines in obesity-associated insulin resistance.
Chenhui Zou (2008)
10.1385/CBB:41:3:415
Regulation of tetrahydrobiopterin synthesis and bioavailability in endothelial cells
W. Shi (2007)
10.1042/BJ3360001
Arginine metabolism: nitric oxide and beyond.
G. Wu (1998)
10.1016/1367-8280(94)90029-9
Insulin stimulates glycolysis and pentose cycle activity in bovine microvascular endothelial cells.
G. Wu (1994)
Dietary L-arginine supplementation reduces fat mass in diet-induced obese rats
W. Jobgen (2009)
10.1007/s00726-008-0075-0
Human Δ1-pyrroline-5-carboxylate synthase: function and regulation
C. Hu (2008)
10.1093/JN/135.4.714
Dietary L-arginine supplementation reduces fat mass in Zucker diabetic fatty rats.
W. J. Fu (2005)
10.1006/abbi.1994.1454
The inhibition of the constitutive bovine endothelial nitric oxide synthase by imidazole and indazole agents.
D. Wolff (1994)
10.1073/PNAS.97.22.12222
Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation.
X. Du (2000)
10.1007/s00726-007-0630-0
Role of neuronal nitric oxide synthase in the regulation of the neuroendocrine stress response in rodents: insights from mutant mice
G. F. Orlando (2007)
10.1152/AJPENDO.00329.2005
Hexosamines, insulin resistance, and the complications of diabetes: current status.
M. Buse (2006)
10.1096/fj.04-1702fje
GTP cyclohydrolase I gene transfer reverses tetrahydrobiopterin deficiency and increases nitric oxide synthesis in endothelial cells and isolated vessels from diabetic rats
C. Meininger (2004)
10.1096/FASEBJ.21.5.A328-B
Dietary arginine supplementation reduces fat mass in diet-induced-obese rats by improving glucose and fatty acid metabolism
W. Jobgen (2007)
10.1152/ajpheart.1995.269.4.H1312
Impaired arginine metabolism and NO synthesis in coronary endothelial cells of the spontaneously diabetic BB rat.
G. Wu (1995)
10.1152/AJPENDO.2001.280.1.E75
Regulatory role of arginase I and II in nitric oxide, polyamine, and proline syntheses in endothelial cells.
H. Li (2001)
10.1016/J.YJMCC.2004.07.006
Co-expression and modulation of neuronal and endothelial nitric oxide synthase in human endothelial cells.
T. Bachetti (2004)
10.1016/S1357-2725(00)00070-4
Stimulation of tetrahydrobiopterin synthesis induced by insulin: possible involvement of phosphatidylinositol 3-kinase.
M. Ishii (2001)
10.1042/bj3570593
Nitric oxide synthases: structure, function and inhibition.
W. K. Alderton (2001)
10.1007/s00125-005-0066-6
Elevations of plasma methylarginines in obesity and ageing are related to insulin sensitivity and rates of protein turnover
E. B. Marliss (2005)
10.1007/s001250051599
Presence of glutamine:fructose-6-phosphate amidotransferase for glucosamine-6-phosphate synthesis in endothelial cells: effects of hyperglycaemia and glutamine
G. Wu (2001)
10.1093/JN/130.11.2626
Arginine nutrition and cardiovascular function.
G. Wu (2000)
10.1007/s00726-008-0148-0
Dietary l-arginine supplementation increases muscle gain and reduces body fat mass in growing-finishing pigs
B. Tan (2008)
10.1042/0264-6021:3490353
Impaired nitric oxide production in coronary endothelial cells of the spontaneously diabetic BB rat is due to tetrahydrobiopterin deficiency.
C. Meininger (2000)
10.1172/JCI117957
Interactions between L-arginine and L-glutamine change endothelial NO production. An effect independent of NO synthase substrate availability.
J. Arnal (1995)
10.2337/DIABETES.48.1.106
Induction of insulin resistance by glucosamine reduces blood flow but not interstitial levels of either glucose or insulin.
A. Holmäng (1999)



This paper is referenced by
10.1016/j.mce.2014.09.007
Environmental factors affecting pregnancy: Endocrine disrupters, nutrients and metabolic pathways
F. Bazer (2014)
10.1080/17461391.2011.635705
The nitrate-nitrite-nitric oxide pathway: Its role in human exercise physiology
S. Bailey (2012)
10.1201/B10449-7
Nutrition, Epigenetics, and Vascular Function
M. C. Satterfield (2010)
The therapeutic effect of dietary nitrate supplementation in healthy adults, individuals with type 2 diabetes mellitus and chronic obstructive pulmonary disease
Anthony I Shepherd (2015)
Dietary Supplementation with Watermelon (Citrullus Ianatus) Juice Enhances Arginine Availability and Modifies Hyperglycemia, Hyperlipidemia and Oxidative Stress in Diabetic Rats .
F. H. A. El-Razek (2011)
Role of Superoxide Dismutase 2 Gene Ala16Val Polymorphism and Total Antioxidant Capacity in Diabetes and its Complications
Katayoun Pourvali (2016)
10.2741/4106
Roles of heat-shock protein 70 in protecting against intestinal mucosal damage.
Xin Wu (2013)
10.1007/s12562-020-01414-4
Effects of dietary proline on growth, physiology, biochemistry and TOR pathway-related gene expression in juvenile spotted drum Nibea diacanthus
Hua. Rong (2020)
10.1007/s00726-013-1551-8
Dietary l-glutamine supplementation increases Pasteurella multocida burden and the expression of its major virulence factors in mice
W. Ren (2013)
10.1201/B14907-2
Physiological Importance of Endothelium
D. Erbaş (2013)
microRNA-223 Regulates Macrophage Polarization and Diet-induced Insulin Resistance
Cong Lin Meng (2013)
10.1007/s00726-017-2490-6
Roles of dietary glycine, proline, and hydroxyproline in collagen synthesis and animal growth
P. Li (2017)
10.2174/1389450119666180821105544
Toll-Like Receptor 4 and Heat-Shock Protein 70: Is it a New Target Pathway for Diabetic Vasculopathies?
Amanda Almeida de Oliveira (2019)
10.1186/gm334
Metabolomic analysis of rat serum in streptozotocin-induced diabetes and after treatment with oral triethylenetetramine (TETA)
M. Ugarte (2012)
10.1007/s00726-012-1328-5
Dynamic changes in blood flow and oxygen consumption in the portal-drained viscera of growing pigs receiving acute administration of l-arginine
Bie Tan (2012)
10.3945/jn.110.131888
Enteral arginine does not increase superior mesenteric arterial blood flow but induces mucosal growth in neonatal pigs.
P. J. Puiman (2011)
10.1007/s12015-012-9398-z
Epigenetic Programming and Risk: The Birthplace of Cardiovascular Disease?
M. C. Vinci (2012)
10.2527/jas.2009-2446
Impacts of amino acid nutrition on pregnancy outcome in pigs: mechanisms and implications for swine production.
G. Wu (2010)
10.2527/jas.2010-3614
Triennial Growth Symposium: important roles for L-glutamine in swine nutrition and production.
G. Wu (2011)
10.1533/9780857095749.3.523
Arginine and immune function.
G. Wu (2013)
10.1016/j.jnutbio.2010.03.012
Dietary L-arginine supplementation differentially regulates expression of lipid-metabolic genes in porcine adipose tissue and skeletal muscle.
B. Tan (2011)
10.1016/j.bcp.2020.113819
Regulation of carbohydrate metabolism by nitric oxide and hydrogen sulfide: Implications in diabetes.
Sevda Gheibi (2020)
10.1097/MCO.0b013e328333c27f
Combined infusion of glutamine and arginine: does it make sense?
M. Coëffier (2010)
10.1095/biolreprod.110.085753
Select Nutrients in the Ovine Uterine Lumen. VIII. Arginine Stimulates Proliferation of Ovine Trophectoderm Cells Through MTOR-RPS6K-RPS6 Signaling Cascade and Synthesis of Nitric Oxide and Polyamines1
Jin-young Kim (2011)
10.1016/J.ANIFEEDSCI.2018.09.007
The relevance of functional amino acids to support the health of growing pigs
N. Floc’h (2018)
Impacts of Maternal Obesity on Metabolic Profiles in Postpartum Ewes
Jason R. McKnight (2011)
10.1007/s00726-015-1992-3
Safety of long-term dietary supplementation with l-arginine in rats
Ying Yang (2015)
10.2147/VHRM.S17801
Cardiovascular dysfunction in obesity and new diagnostic imaging techniques: the role of noninvasive image methods
J. A. Barbosa (2011)
10.1016/j.ejphar.2019.02.029
Vaccarin ameliorates insulin resistance and steatosis by activating the AMPK signaling pathway
Yueyue Lei (2019)
10.21451/1984-3143-AR888
Pregnancy recognition signals in mammals: the roles of interferons and estrogens
F. Bazer (2017)
Lumen illuminated : Intestinal defense mechanisms in the neonate
P. Puiman (2010)
10.1007/s00726-009-0269-0
Amino acids: metabolism, functions, and nutrition
G. Wu (2009)
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