Skip to main content
SpringerLink
Log in

Antioxidants and Diabetes

  • Reference work entry
  • First Online:
Systems Biology of Free Radicals and Antioxidants

  • 272 Accesses

Abstract

Diabetes has emerged as a major threat to worldwide health. The mechanisms underlying the disease are unknown; however, there is growing evidence that excess generation of reactive oxygen species, largely due to hyperglycemia, causes oxidative stress in a variety of tissues. Oxidative stress results either from an increase in free radical production or a decrease in endogenous antioxidant defenses, or both. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are products of normal cellular metabolism. ROS and RNS are well recognized for playing a dual role as both deleterious and beneficial species. In type 2 diabetic patients, oxidative stress is closely associated with chronic inflammation leading to potential tissue damage. This chapter considers the therapeutic opportunities presented by currently used pharmacological agents which possess direct and indirect antioxidant properties as well as new potential antioxidant substances. There are many endogenous factors (antioxidants, vitamins, antioxidant enzymes, chelators of metal ions) that can serve as endogenous modulators of the production and action of endogenous reactive species. Clinical trials with antioxidant vitamins investigating the progression of diabetic complications produced negative or inconclusive results. This lack of efficacy might also result from the fact that we are acting much too late in the signaling cascade, at a time at which initiation of the alterations in the redox status are already further engaged. Another strategy for modulating oxidative stress in humans is via exploitation of the pleiotropic properties of drugs directed primarily at other pathologies, these drugs being indirect antioxidants. The ideal approach to antioxidant therapy requires, for vascular disease, stimulation of nitric oxide production and simultaneous inhibition of superoxide production. It is important to develop new compounds that target key vascular ROS-producing enzymes and mimic endogenous antioxidant. This strategy might prove clinically relevant in preventing the development and/or retarding the progression of diabetes-associated vascular complications.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 1,999.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 2,999.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abhary S, Kasmeridis N, Burdon KP, Kuot A, Whiting MJ, Yew WP, Petrovsky N, Craig JE (2009) Diabetic retinopathy is associated with elevated serum asymmetric and symmetric dimethylarginines. Diabetes Care 32:2084–2086

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ali TK, Matragoon S, Pillai BA, Liou GI, El-Remessy AB (2008) Peroxynitrite mediates retinal neurodegeneration by inhibiting nerve growth factor survival signaling in experimental and human diabetes. Diabetes 57:889–898

    CAS  PubMed  Google Scholar 

  • Anders MW (2011) Putting bioactivation reactions to work: targeting antioxidants to mitochondria. Chem Biol Interact 192:8–13

    CAS  PubMed  Google Scholar 

  • Angelin B, Larsson TE, Rudling M (2012) Circulating fibroblast growth factors as metabolic regulators–a critical appraisal. Cell Metab 16:693–705

    CAS  PubMed  Google Scholar 

  • Asensio-Lopez MC, Lax A, Pascual-Figal DA, Valdes M, Sanchez-Mas J (2011) Metformin protects against doxorubicin-induced cardiotoxicity: involvement of the adiponectin cardiac system. Free Radic Biol Med 51:1861–1871

    CAS  PubMed  Google Scholar 

  • Ayaz M, Ozdemir S, Ugur M, Vassort G, Turan B (2004) Effects of selenium on altered mechanical and electrical cardiac activities of diabetic rat. Arch Biochem Biophys 426:83–90

    CAS  PubMed  Google Scholar 

  • Batinic-Haberle I, Reboucas JS, Spasojevic I (2010) Superoxide dismutase mimics: chemistry, pharmacology, and therapeutic potential. Antioxid Redox Signal 13:877–918

    CAS  PubMed Central  PubMed  Google Scholar 

  • Batinic-Haberle I, Rajic Z, Tovmasyan A, Reboucas JS, Ye X, Leong KW, Dewhirst MW, Vujaskovic Z, Benov L, Spasojevic I (2011) Diverse functions of cationic Mn(III) N-substituted pyridylporphyrins, recognized as SOD mimics. Free Radic Biol Med 51:1035–1053

    CAS  PubMed Central  PubMed  Google Scholar 

  • Beckman JA, Creager MA, Libby P (2002) Diabetes and atherosclerosis: epidemiology, pathophysiology, and management. JAMA 287:2570–2581

    CAS  PubMed  Google Scholar 

  • Blackburn GL (2010) From bench to bedside: novel mechanisms and therapeutic advances through the development of selective peroxisome proliferator-activated receptor gamma modulators. Am J Clin Nutr 91:251S–253S

    CAS  PubMed  Google Scholar 

  • Blum S, Vardi M, Brown JB, Russell A, Milman U, Shapira C, Levy NS, Miller-Lotan R, Asleh R, Levy AP (2010) Vitamin E reduces cardiovascular disease in individuals with diabetes mellitus and the haptoglobin 2-2 genotype. Pharmacogenomics 11:675–684

    CAS  PubMed Central  PubMed  Google Scholar 

  • Brown BG, Crowley J (2005) Is there any hope for vitamin E? JAMA 293:1387–1390

    CAS  PubMed  Google Scholar 

  • Camara AK, Lesnefsky EJ, Stowe DF (2010) Potential therapeutic benefits of strategies directed to mitochondria. Antioxid Redox Signal 13:279–347

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cat AN, Touyz RM (2011) A new look at the renin-angiotensin system–focusing on the vascular system. Peptides 32:2141–2150

    Google Scholar 

  • Cheng X, Siow RC, Mann GE (2011) Impaired redox signaling and antioxidant gene expression in endothelial cells in diabetes: a role for mitochondria and the nuclear factor-E2-related factor 2-kelch-like ECH-associated protein 1 defense pathway. Antioxid Redox Signal 14:469–487

    CAS  PubMed  Google Scholar 

  • Chicco AJ, Sparagna GC (2007) Role of cardiolipin alterations in mitochondrial dysfunction and disease. Am J Physiol Cell Physiol 292:C33–C44

    CAS  PubMed  Google Scholar 

  • Chung SS, Kim M, Lee JS, Ahn BY, Jung HS, Lee HM, Park KS (2011) Mechanism for antioxidative effects of thiazolidinediones in pancreatic beta-cells. Am J Physiol Endocrinol Metab 301:E912–E921

    CAS  PubMed  Google Scholar 

  • Clark RB (2002) The role of PPARs in inflammation and immunity. J Leukoc Biol 71:388–400

    CAS  PubMed  Google Scholar 

  • Clermont G, Lecour S, Cabanne JF, Motte G, Guilland JC, Chevet D, Rochette L (2001) Vitamin E-coated dialyzer reduces oxidative stress in hemodialysis patients. Free Radic Biol Med 31:233–241

    CAS  PubMed  Google Scholar 

  • Cohen G, Riahi Y, Shamni O, Guichardant M, Chatgilialoglu C, Ferreri C, Kaiser N, Sasson S (2011) Role of lipid peroxidation and PPAR-delta in amplifying glucose-stimulated insulin secretion. Diabetes 60:2830–2842

    CAS  PubMed Central  PubMed  Google Scholar 

  • Combs TP, Wagner JA, Berger J, Doebber T, Wang WJ, Zhang BB, Tanen M, Berg AH, O’Rahilly S, Savage DB, Chatterjee K, Weiss S, Larson PJ, Gottesdiener KM, Gertz BJ, Charron MJ, Scherer PE, Moller DE (2002) Induction of adipocyte complement-related protein of 30 kilodaltons by PPARgamma agonists: a potential mechanism of insulin sensitization. Endocrinology 143:998–1007

    CAS  PubMed  Google Scholar 

  • Cooke JP (2000) Does ADMA cause endothelial dysfunction? Arterioscler Thromb Vasc Biol 20:2032–2037

    CAS  PubMed  Google Scholar 

  • Courderot-Masuyer C, Lahet JJ, Verges B, Brun JM, Rochette L (2000) Ascorbyl free radical release in diabetic patients. Cell Mol Biol (Noisy-le-Grand) 46:1397–1401

    CAS  Google Scholar 

  • Day BJ (2009) Catalase and glutathione peroxidase mimics. Biochem Pharmacol 77:285–296

    CAS  PubMed Central  PubMed  Google Scholar 

  • de Haan JB, Cooper ME (2011) Targeted antioxidant therapies in hyperglycemia-mediated endothelial dysfunction. Front Biosci (Schol Ed) 3:709–729

    Google Scholar 

  • Demozay D, Mas JC, Rocchi S, Van Obberghen E (2008) FALDH reverses the deleterious action of oxidative stress induced by lipid peroxidation product 4-hydroxynonenal on insulin signaling in 3T3-L1 adipocytes. Diabetes 57:1216–1226

    CAS  PubMed  Google Scholar 

  • Drel VR, Pacher P, Stavniichuk R, Xu W, Zhang J, Kuchmerovska TM, Slusher B, Obrosova IG (2011) Poly(ADP-ribose)polymerase inhibition counteracts renal hypertrophy and multiple manifestations of peripheral neuropathy in diabetic akita mice. Int J Mol Med 28:629–635

    CAS  PubMed Central  PubMed  Google Scholar 

  • Du X, Edelstein D, Brownlee M (2008) Oral benfotiamine plus alpha-lipoic acid normalises complication-causing pathways in type 1 diabetes. Diabetologia 51:1930–1932

    CAS  PubMed  Google Scholar 

  • Erejuwa OO, Sulaiman SA, Wahab MS, Salam SK, Salleh MS, Gurtu S (2011) Comparison of antioxidant effects of honey, glibenclamide, metformin, and their combinations in the kidneys of streptozotocin-induced diabetic rats. Int J Mol Sci 12:829–843

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fardoun RZ (2007) The use of vitamin E in type 2 diabetes mellitus. Clin Exp Hypertens 29:135–148

    CAS  PubMed  Google Scholar 

  • Finck BN, Lehman JJ, Leone TC, Welch MJ, Bennett MJ, Kovacs A, Han X, Gross RW, Kozak R, Lopaschuk GD, Kelly DP (2002) The cardiac phenotype induced by PPARalpha overexpression mimics that caused by diabetes mellitus. J Clin Invest 109:121–130

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fukudome D, Matsuda M, Kawasaki T, Ago Y, Matsuda T (2008) The radical scavenger edaravone counteracts diabetes in multiple low-dose streptozotocin-treated mice. Eur J Pharmacol 583:164–169

    CAS  PubMed  Google Scholar 

  • Garcia-Bailo B, El-Sohemy A, Haddad PS, Arora P, Benzaied F, Karmali M, Badawi A (2011) Vitamins D, C, and E in the prevention of type 2 diabetes mellitus: modulation of inflammation and oxidative stress. Biologics 5:7–19

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gargari BP, Aghamohammadi V, Aliasgharzadeh A (2011) Effect of folic acid supplementation on biochemical indices in overweight and obese men with type 2 diabetes. Diabetes Res Clin Pract 94:33–38

    CAS  PubMed  Google Scholar 

  • Ghibu S, Lauzier B, Delemasure S, Amoureux S, Sicard P, Vergely C, Muresan A, Mogosan C, Rochette L (2009) Antioxidant properties of alpha-lipoic acid: effects on red blood membrane permeability and adaptation of isolated rat heart to reversible ischemia. Mol Cell Biochem 320:141–148

    CAS  PubMed  Google Scholar 

  • Giacco F, Brownlee M (2010) Oxidative stress and diabetic complications. Circ Res 107:1058–1070

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gibson KR, Winterburn TJ, Barrett F, Sharma S, MacRury SM, Megson IL (2011) Therapeutic potential of N-acetylcysteine as an antiplatelet agent in patients with type-2 diabetes. Cardiovasc Diabetol 10:43

    CAS  PubMed Central  PubMed  Google Scholar 

  • Golbidi S, Laher I (2010) Antioxidant therapy in human endocrine disorders. Med Sci Monit 16:RA9–RA24

    CAS  PubMed  Google Scholar 

  • Gori T, Munzel T (2011) Oxidative stress and endothelial dysfunction: therapeutic implications. Ann Med 43:259–272

    CAS  PubMed  Google Scholar 

  • Graves DT, Kayal RA (2008) Diabetic complications and dysregulated innate immunity. Front Biosci 13:1227–1239

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gray B, Swick J, Ronnenberg AG (2011) Vitamin E and adiponectin: proposed mechanism for vitamin E-induced improvement in insulin sensitivity. Nutr Rev 69:155–161

    PubMed  Google Scholar 

  • Groeger AL, Freeman BA (2010) Signaling actions of electrophiles: anti-inflammatory therapeutic candidates. Mol Interv 10:39–50

    CAS  PubMed Central  PubMed  Google Scholar 

  • Halliwell B (2011) Free radicals and antioxidants – quo vadis? Trends Pharmacol Sci 32:125–130

    CAS  PubMed  Google Scholar 

  • Halliwell B, Gutteridge JM (1995) The definition and measurement of antioxidants in biological systems. Free Radic Biol Med 18:125–126

    CAS  PubMed  Google Scholar 

  • Hamilton SJ, Chew GT, Watts GF (2009) Coenzyme Q10 improves endothelial dysfunction in statin-treated type 2 diabetic patients. Diabetes Care 32:810–812

    PubMed Central  PubMed  Google Scholar 

  • Hasegawa T, Okada K, Okita Y, Pinsky DJ (2011) Antioxidant properties of pioglitazone limit nicotinamide adenine dinucleotide phosphate hydrogen oxidase and augment superoxide dismutase activity in cardiac allotransplantation. J Heart Lung Transplant 30:1186–1196

    PubMed  Google Scholar 

  • Head KA (2006) Peripheral neuropathy: pathogenic mechanisms and alternative therapies. Altern Med Rev 11:294–329

    PubMed  Google Scholar 

  • Heald M, Cawthorne MA (2011) Dual acting and pan-PPAR activators as potential anti-diabetic therapies. Handb Exp Pharmacol 203:35–51

    CAS  PubMed  Google Scholar 

  • Hecht R, Li YS, Sun J, Belouski E, Hall M, Hager T, Yie J, Wang W, Winters D, Smith S, Spahr C, Tam LT, Shen Z, Stanislaus S, Chinookoswong N, Lau Y, Sickmier A, Michaels ML, Boone T, Veniant MM, Xu J (2012) Rationale-based engineering of a potent long-acting FGF21 analog for the treatment of type 2 diabetes. PLoS One 7:e49345

    CAS  PubMed Central  PubMed  Google Scholar 

  • Heitzer T, Finckh B, Albers S, Krohn K, Kohlschutter A, Meinertz T (2001) Beneficial effects of alpha-lipoic acid and ascorbic acid on endothelium-dependent, nitric oxide-mediated vasodilation in diabetic patients: relation to parameters of oxidative stress. Free Radic Biol Med 31:53–61

    CAS  PubMed  Google Scholar 

  • Heller B, Wang ZQ, Wagner EF, Radons J, Burkle A, Fehsel K, Burkart V, Kolb H (1995) Inactivation of the poly(ADP-ribose) polymerase gene affects oxygen radical and nitric oxide toxicity in islet cells. J Biol Chem 270:11176–11180

    CAS  PubMed  Google Scholar 

  • Hou X, Song J, Li XN, Zhang L, Wang X, Chen L, Shen YH (2010) Metformin reduces intracellular reactive oxygen species levels by upregulating expression of the antioxidant thioredoxin via the AMPK-FOXO3 pathway. Biochem Biophys Res Commun 396:199–205

    CAS  PubMed  Google Scholar 

  • Ikeda Y, Tajima S, Yoshida S, Yamano N, Kihira Y, Ishizawa K, Aihara K, Tomita S, Tsuchiya K, Tamaki T (2011) Deferoxamine promotes angiogenesis via the activation of vascular endothelial cell function. Atherosclerosis 215:339–347

    CAS  PubMed  Google Scholar 

  • Jiang C, Ting AT, Seed B (1998) PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 391:82–86

    CAS  PubMed  Google Scholar 

  • Johansen JS, Harris AK, Rychly DJ, Ergul A (2005) Oxidative stress and the use of antioxidants in diabetes: linking basic science to clinical practice. Cardiovasc Diabetol 4:5

    PubMed Central  PubMed  Google Scholar 

  • Jomova K, Valko M (2011) Advances in metal-induced oxidative stress and human disease. Toxicology 283:65–87

    CAS  PubMed  Google Scholar 

  • Jones DP (2006) Redefining oxidative stress. Antioxid Redox Signal 8:1865–1879

    CAS  PubMed  Google Scholar 

  • Jones DP, Go YM (2010) Redox compartmentalization and cellular stress. Diabetes Obes Metab 12(Suppl 2):116–125

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kahn BB, Flier JS (2000) Obesity and insulin resistance. J Clin Invest 106:473–481

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kalupahana NS, Moustaid-Moussa N, Claycombe KJ (2012) Immunity as a link between obesity and insulin resistance. Mol Aspects Med 33:26–34

    CAS  PubMed  Google Scholar 

  • Kasapis C, Thompson PD (2005) The effects of physical activity on serum C-reactive protein and inflammatory markers: a systematic review. J Am Coll Cardiol 45:1563–1569

    CAS  PubMed  Google Scholar 

  • Kassan M, Choi SK, Galan M, Bishop A, Umezawa K, Trebak M, Belmadani S, Matrougui K (2013) Enhanced NFkappaB activity impairs vascular function through PARP-1, SP-1 and COX2-dependent mechanisms in type 2 diabetes. Diabetes (in press)

    Google Scholar 

  • Kawai H, Nakai H, Suga M, Yuki S, Watanabe T, Saito KI (1997) Effects of a novel free radical scavenger, MCl-186, on ischemic brain damage in the rat distal middle cerebral artery occlusion model. J Pharmacol Exp Ther 281:921–927

    CAS  PubMed  Google Scholar 

  • Kelly AS, Thelen AM, Kaiser DR, Gonzalez-Campoy JM, Bank AJ (2007) Rosiglitazone improves endothelial function and inflammation but not asymmetric dimethylarginine or oxidative stress in patients with type 2 diabetes mellitus. Vasc Med 12:311–318

    PubMed  Google Scholar 

  • Kodiha M, Stochaj U (2012) Nuclear transport: a switch for the oxidative stress-signaling circuit? J Signal Transduct 2012:208650

    PubMed Central  PubMed  Google Scholar 

  • Koenitzer JR, Freeman BA (2010) Redox signaling in inflammation: interactions of endogenous electrophiles and mitochondria in cardiovascular disease. Ann N Y Acad Sci 1203:45–52

    CAS  PubMed  Google Scholar 

  • Korandji C, Zeller M, Guilland JC, Vergely C, Sicard P, Duvillard L, Gambert P, Moreau D, Cottin Y, Rochette L (2007) Asymmetric dimethylarginine (ADMA) and hyperhomocysteinemia in patients with acute myocardial infarction. Clin Biochem 40:66–72

    CAS  PubMed  Google Scholar 

  • Korandji C, Zeller M, Guilland JC, Collin B, Lauzier B, Sicard P, Duvillard L, Goirand F, Moreau D, Cottin Y, Rochette L, Vergely C (2011) Time course of asymmetric dimethylarginine (ADMA) and oxidative stress in fructose-hypertensive rats: a model related to metabolic syndrome. Atherosclerosis 214:310–315

    CAS  PubMed  Google Scholar 

  • Kralisch S, Fasshauer M (2011) Fibroblast growth factor 21: effects on carbohydrate and lipid metabolism in health and disease. Curr Opin Clin Nutr Metab Care 14:354–359

    CAS  PubMed  Google Scholar 

  • Krusinova E, Pelikanova T (2008) Fatty acid binding proteins in adipose tissue: a promising link between metabolic syndrome and atherosclerosis? Diabetes Res Clin Pract 82(Suppl 2):S127–S134

    CAS  PubMed  Google Scholar 

  • Lahet JJ, Courderot-Masuyer C, Lenfant F, Tatou E, Vergely C, David M, Rochette L (2004) The influence of extracorporeal circulation on the susceptibility of erythrocytes to oxidative stress. Free Radic Res 38:683–689

    CAS  PubMed  Google Scholar 

  • Landrier JF, Gouranton E, El Yazidi C, Malezet C, Balaguer P, Borel P, Amiot MJ (2009) Adiponectin expression is induced by vitamin E via a peroxisome proliferator-activated receptor gamma-dependent mechanism. Endocrinology 150:5318–5325

    CAS  PubMed  Google Scholar 

  • Lauzier B, Sicard P, Bouchot O, Delemasure S, Moreau D, Vergely C, Rochette L (2007) A peroxynitrite decomposition catalyst: FeTPPS confers cardioprotection during reperfusion after cardioplegic arrest in a working isolated rat heart model. Fundam Clin Pharmacol 21:173–180

    CAS  PubMed  Google Scholar 

  • Lee JM, Li J, Johnson DA, Stein TD, Kraft AD, Calkins MJ, Jakel RJ, Johnson JA (2005) Nrf2, a multi-organ protector? FASEB J 19:1061–1066

    PubMed  Google Scholar 

  • Lee JH, Park GH, Lee YK, Park JH (2011) Changes in the arginine methylation of organ proteins during the development of diabetes mellitus. Diabetes Res Clin Pract 94:111–118

    CAS  PubMed  Google Scholar 

  • Li MD, Yang X (2011) A retrospective on nuclear receptor regulation of inflammation: lessons from GR and PPARs. PPAR Res 2011:742785

    PubMed Central  PubMed  Google Scholar 

  • Li WJ, Shin MK, Oh SJ (2011) Poly(ADP-ribose) polymerase is involved in the development of diabetic cystopathy via regulation of nuclear factor kappa B. Urology 77(1265):e1–e8

    Google Scholar 

  • Liu Q, Sun L, Tan Y, Wang G, Lin X, Cai L (2009) Role of iron deficiency and overload in the pathogenesis of diabetes and diabetic complications. Curr Med Chem 16:113–129

    CAS  PubMed  Google Scholar 

  • Love A, Cotter MA, Cameron NE (1996) Effects of the sulphydryl donor N-acetyl-L-cysteine on nerve conduction, perfusion, maturation and regeneration following freeze damage in diabetic rats. Eur J Clin Invest 26:698–706

    CAS  PubMed  Google Scholar 

  • Luther JM, Brown NJ (2011) The renin-angiotensin-aldosterone system and glucose homeostasis. Trends Pharmacol Sci 32:734–739

    CAS  PubMed Central  PubMed  Google Scholar 

  • Marchesi C, Schiffrin EL (2008) Peroxisome proliferator-activated receptors and the vascular system: beyond their metabolic effects. J Am Soc Hypertens 2:227–238

    PubMed  Google Scholar 

  • Martin C, Dubouchaud H, Mosoni L, Chardigny JM, Oudot A, Fontaine E, Vergely C, Keriel C, Rochette L, Leverve X, Demaison L (2007) Abnormalities of mitochondrial functioning can partly explain the metabolic disorders encountered in sarcopenic gastrocnemius. Aging Cell 6:165–177

    CAS  PubMed  Google Scholar 

  • Mazzone T, Chait A, Plutzky J (2008) Cardiovascular disease risk in type 2 diabetes mellitus: insights from mechanistic studies. Lancet 371:1800–1809

    CAS  PubMed Central  PubMed  Google Scholar 

  • Meijer RI, Serne EH, Smulders YM, van Hinsbergh VW, Yudkin JS, Eringa EC (2011) Perivascular adipose tissue and its role in type 2 diabetes and cardiovascular disease. Curr Diab Rep 11:211–217

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mezawa M, Takemoto M, Onishi S, Ishibashi R, Ishikawa T, Yamaga M, Fujimoto M, Okabe E, He P, Kobayashi K, Yokote K (2012) The reduced form of coenzyme Q10 improves glycemic control in patients with type 2 diabetes: an open label pilot study. Biofactors 38:416–421

    CAS  PubMed  Google Scholar 

  • Miao CY, Li ZY (2012) The role of perivascular adipose tissue in vascular smooth muscle cell growth. Br J Pharmacol 165:643–658

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mihm MJ, Wattanapitayakul SK, Piao SF, Hoyt DG, Bauer JA (2003) Effects of angiotensin II on vascular endothelial cells: formation of receptor-mediated reactive nitrogen species. Biochem Pharmacol 65:1189–1197

    CAS  PubMed  Google Scholar 

  • Miller ER 3rd, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E (2005) Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 142:37–46

    CAS  PubMed  Google Scholar 

  • Montezano AC, Touyz RM (2012) Reactive oxygen species and endothelial function – role of nitric oxide synthase uncoupling and nox family nicotinamide adenine dinucleotide phosphate oxidases. Basic Clin Pharmacol Toxicol 110:87–94

    CAS  PubMed  Google Scholar 

  • Munzel T, Sinning C, Post F, Warnholtz A, Schulz E (2008) Pathophysiology, diagnosis and prognostic implications of endothelial dysfunction. Ann Med 40:180–196

    PubMed  Google Scholar 

  • Munzel T, Gori T, Bruno RM, Taddei S (2010) Is oxidative stress a therapeutic target in cardiovascular disease? Eur Heart J 31:2741–2748

    PubMed  Google Scholar 

  • Negi G, Kumar A, Joshi RP, Sharma SS (2011) Oxidative stress and Nrf2 in the pathophysiology of diabetic neuropathy: old perspective with a new angle. Biochem Biophys Res Commun 408:1–5

    CAS  PubMed  Google Scholar 

  • Newsholme P, Haber EP, Hirabara SM, Rebelato EL, Procopio J, Morgan D, Oliveira-Emilio HC, Carpinelli AR, Curi R (2007) Diabetes associated cell stress and dysfunction: role of mitochondrial and non-mitochondrial ROS production and activity. J Physiol 583:9–24

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T, Kaneda Y, Yorek MA, Beebe D, Oates PJ, Hammes HP, Giardino I, Brownlee M (2000) Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 404:787–790

    CAS  PubMed  Google Scholar 

  • Nunes SF, Figueiredo IV, Pereira JS, de Lemos ET, Reis F, Teixeira F, Caramona MM (2011) Monoamine oxidase and semicarbazide-sensitive amine oxidase kinetic analysis in mesenteric arteries of patients with type 2 diabetes. Physiol Res 60:309–315

    CAS  PubMed  Google Scholar 

  • Obrosova IG, Drel VR, Oltman CL, Mashtalir N, Tibrewala J, Groves JT, Yorek MA (2007) Role of nitrosative stress in early neuropathy and vascular dysfunction in streptozotocin-diabetic rats. Am J Physiol Endocrinol Metab 293:E1645–E1655

    CAS  PubMed  Google Scholar 

  • Oudot A, Vergely C, Ecarnot-Laubriet A, Rochette L (2005) Pharmacological concentration of angiotensin-(1-7) activates NADPH oxidase after ischemia-reperfusion in rat heart through AT1 receptor stimulation. Regul Pept 127:101–110

    CAS  PubMed  Google Scholar 

  • Oudot A, Martin C, Busseuil D, Vergely C, Demaison L, Rochette L (2006) NADPH oxidases are in part responsible for increased cardiovascular superoxide production during aging. Free Radic Biol Med 40:2214–2222

    CAS  PubMed  Google Scholar 

  • Pacher P, Szabo C (2008) Role of the peroxynitrite-poly(ADP-ribose) polymerase pathway in human disease. Am J Pathol 173:2–13

    CAS  PubMed Central  PubMed  Google Scholar 

  • Packer L, Witt EH, Tritschler HJ (1995) Alpha-lipoic acid as a biological antioxidant. Free Radic Biol Med 19:227–250

    CAS  PubMed  Google Scholar 

  • Pazdro R, Burgess JR (2010) The role of vitamin E and oxidative stress in diabetes complications. Mech Ageing Dev 131:276–286

    CAS  PubMed  Google Scholar 

  • Pi J, Zhang Q, Fu J, Woods CG, Hou Y, Corkey BE, Collins S, Andersen ME (2010) ROS signaling, oxidative stress and Nrf2 in pancreatic beta-cell function. Toxicol Appl Pharmacol 244:77–83

    CAS  PubMed Central  PubMed  Google Scholar 

  • Piganelli JD, Flores SC, Cruz C, Koepp J, Batinic-Haberle I, Crapo J, Day B, Kachadourian R, Young R, Bradley B, Haskins K (2002) A metalloporphyrin-based superoxide dismutase mimic inhibits adoptive transfer of autoimmune diabetes by a diabetogenic T-cell clone. Diabetes 51:347–355

    CAS  PubMed  Google Scholar 

  • Rabbani N, Alam SS, Riaz S, Larkin JR, Akhtar MW, Shafi T, Thornalley PJ (2009) High-dose thiamine therapy for patients with type 2 diabetes and microalbuminuria: a randomised, double-blind placebo-controlled pilot study. Diabetologia 52:208–212

    CAS  PubMed  Google Scholar 

  • Rabelo LA, Alenina N, Bader M (2011) ACE2-angiotensin-(1-7)-Mas axis and oxidative stress in cardiovascular disease. Hypertens Res 34:154–160

    CAS  PubMed  Google Scholar 

  • Rajaraman G, Wang GQ, Yan J, Jiang P, Gong Y, Burczynski FJ (2007) Role of cytosolic liver fatty acid binding protein in hepatocellular oxidative stress: effect of dexamethasone and clofibrate treatment. Mol Cell Biochem 295:27–34

    CAS  PubMed  Google Scholar 

  • Renna NF, Lembo C, Diez E, Miatello RM (2013) Role of renin-angiotensin system and oxidative stress on vascular inflammation in insulin resistence model. Int J Hypertens 2013:420979

    CAS  PubMed Central  PubMed  Google Scholar 

  • Richard C, Lauzier B, Delemasure S, Talbot S, Ghibu S, Collin B, Senecal J, Menetrier F, Vergely C, Couture R, Rochette L (2008) Effects of angiotensin-1 converting enzyme inhibition on oxidative stress and bradykinin receptor expression during doxorubicin-induced cardiomyopathy in rats. J Cardiovasc Pharmacol 52:278–285

    CAS  PubMed  Google Scholar 

  • Rochette L, Vergely C (2008a) Forgotten radicals in biology. Int J Biomed Sci 4:255–259

    Google Scholar 

  • Rochette L, Vergely C (2008b) Hydrogen sulfide (H2S), an endogenous gas with odor of rotten eggs might be a cardiovascular function regulator. Ann Cardiol Angeiol (Paris) 57:136–138

    CAS  Google Scholar 

  • Roede JR, Go YM, Jones DP (2012) Redox equivalents and mitochondrial bioenergetics. Methods Mol Biol 810:249–280

    CAS  PubMed  Google Scholar 

  • Sagara M, Satoh J, Wada R, Yagihashi S, Takahashi K, Fukuzawa M, Muto G, Muto Y, Toyota T (1996) Inhibition of development of peripheral neuropathy in streptozotocin-induced diabetic rats with N-acetylcysteine. Diabetologia 39:263–269

    CAS  PubMed  Google Scholar 

  • Sanmartin C, Plano D, Font M, Palop JA (2011) Selenium and clinical trials: new therapeutic evidence for multiple diseases. Curr Med Chem 18:4635–4650

    CAS  PubMed  Google Scholar 

  • Satoh K, Ikeda Y, Shioda S, Tobe T, Yoshikawa T (2002) Edarabone scavenges nitric oxide. Redox Rep 7:219–222

    CAS  PubMed  Google Scholar 

  • Satoh N, Ogawa Y, Usui T, Tagami T, Kono S, Uesugi H, Sugiyama H, Sugawara A, Yamada K, Shimatsu A, Kuzuya H, Nakao K (2003) Antiatherogenic effect of pioglitazone in type 2 diabetic patients irrespective of the responsiveness to its antidiabetic effect. Diabetes Care 26:2493–2499

    CAS  PubMed  Google Scholar 

  • Sawa T, Ihara H, Akaike T (2011) Antioxidant effect of a nitrated cyclic nucleotide functioning as an endogenous electrophile. Curr Top Med Chem 11:1854–1860

    CAS  PubMed  Google Scholar 

  • Schmid U, Stopper H, Heidland A, Schupp N (2008) Benfotiamine exhibits direct antioxidative capacity and prevents induction of DNA damage in vitro. Diabetes Metab Res Rev 24:371–377

    CAS  PubMed  Google Scholar 

  • Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM (2009) Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys Acta 1790:1149–1160

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shekelle PG, Rich MW, Morton SC, Atkinson CS, Tu W, Maglione M, Rhodes S, Barrett M, Fonarow GC, Greenberg B, Heidenreich PA, Knabel T, Konstam MA, Steimle A, Warner Stevenson L (2003) Efficacy of angiotensin-converting enzyme inhibitors and beta-blockers in the management of left ventricular systolic dysfunction according to race, gender, and diabetic status: a meta-analysis of major clinical trials. J Am Coll Cardiol 41:1529–1538

    CAS  PubMed  Google Scholar 

  • Sicard P, Acar N, Gregoire S, Lauzier B, Bron AM, Creuzot-Garcher C, Bretillon L, Vergely C, Rochette L (2007) Influence of rosuvastatin on the NAD(P)H oxidase activity in the retina and electroretinographic response of spontaneously hypertensive rats. Br J Pharmacol 151:979–986

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sicard P, Delemasure S, Korandji C, Segueira-Le Grand A, Lauzier B, Guilland JC, Duvillard L, Zeller M, Cottin Y, Vergely C, Rochette L (2008) Anti-hypertensive effects of rosuvastatin are associated with decreased inflammation and oxidative stress markers in hypertensive rats. Free Radic Res 42:226–236

    CAS  PubMed  Google Scholar 

  • Simo R, Hernandez C (2009) Advances in the medical treatment of diabetic retinopathy. Diabetes Care 32:1556–1562

    CAS  PubMed Central  PubMed  Google Scholar 

  • Smith HS, Argoff CE (2011) Pharmacological treatment of diabetic neuropathic pain. Drugs 71:557–589

    CAS  PubMed  Google Scholar 

  • Sodhi RK, Singh N, Jaggi AS (2010) Poly(ADP-ribose) polymerase-1 (PARP-1) and its therapeutic implications. Vascul Pharmacol 53:77–87

    CAS  PubMed  Google Scholar 

  • Steinberg D, Witztum JL (2002) Is the oxidative modification hypothesis relevant to human atherosclerosis? Do the antioxidant trials conducted to date refute the hypothesis? Circulation 105:2107–2111

    PubMed  Google Scholar 

  • Stephens JW, Khanolkar MP, Bain SC (2009) The biological relevance and measurement of plasma markers of oxidative stress in diabetes and cardiovascular disease. Atherosclerosis 202:321–329

    CAS  PubMed  Google Scholar 

  • Swaminathan S, Fonseca VA, Alam MG, Shah SV (2007) The role of iron in diabetes and its complications. Diabetes Care 30:1926–1933

    CAS  PubMed  Google Scholar 

  • Swislocki AL, Siegel D, Jialal I (2012) Pharmacotherapy for the metabolic syndrome. Curr Vasc Pharmacol 10:187–205

    CAS  PubMed  Google Scholar 

  • Szabo C, Virag L, Cuzzocrea S, Scott GS, Hake P, O’Connor MP, Zingarelli B, Salzman A, Kun E (1998) Protection against peroxynitrite-induced fibroblast injury and arthritis development by inhibition of poly(ADP-ribose) synthase. Proc Natl Acad Sci USA 95:3867–3872

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tajima S, Ikeda Y, Sawada K, Yamano N, Horinouchi Y, Kihira Y, Ishizawa K, Izawa-Ishizawa Y, Kawazoe K, Tomita S, Minakuchi K, Tsuchiya K, Tamaki T (2012) Iron reduction by deferoxamine leads to amelioration of adiposity via the regulation of oxidative stress and inflammation in obese and type 2 diabetes KKAy mice. Am J Physiol Endocrinol Metab 302:E77–E86

    CAS  PubMed  Google Scholar 

  • Tarnow L, Hovind P, Teerlink T, Stehouwer CD, Parving HH (2004) Elevated plasma asymmetric dimethylarginine as a marker of cardiovascular morbidity in early diabetic nephropathy in type 1 diabetes. Diabetes Care 27:765–769

    CAS  PubMed  Google Scholar 

  • Teixeira-Lemos E, Nunes S, Teixeira F, Reis F (2011) Regular physical exercise training assists in preventing type 2 diabetes development: focus on its antioxidant and anti-inflammatory properties. Cardiovasc Diabetol 10:12

    PubMed Central  PubMed  Google Scholar 

  • Touyz RM, Schiffrin EL (2006) Peroxisome proliferator-activated receptors in vascular biology-molecular mechanisms and clinical implications. Vascul Pharmacol 45:19–28

    CAS  PubMed  Google Scholar 

  • Vassort G, Turan B (2010) Protective role of antioxidants in diabetes-induced cardiac dysfunction. Cardiovasc Toxicol 10:73–86

    CAS  PubMed  Google Scholar 

  • Vergely C, Maupoil V, Benderitter M, Rochette L (1998) Influence of the severity of myocardial ischemia on the intensity of ascorbyl free radical release and on post-ischemic recovery during reperfusion. Free Radic Biol Med 24:470–479

    CAS  PubMed  Google Scholar 

  • Vergely C, Maupoil V, Clermont G, Bril A, Rochette L (2003) Identification and quantification of free radicals during myocardial ischemia and reperfusion using electron paramagnetic resonance spectroscopy. Arch Biochem Biophys 420:209–216

    CAS  PubMed  Google Scholar 

  • Villalba JM, Parrado C, Santos-Gonzalez M, Alcain FJ (2010) Therapeutic use of coenzyme Q10 and coenzyme Q10-related compounds and formulations. Expert Opin Investig Drugs 19:535–554

    CAS  PubMed  Google Scholar 

  • Vinik A, Parson H, Ullal J (2006) The role of PPARs in the microvascular dysfunction in diabetes. Vascul Pharmacol 45:54–64

    CAS  PubMed  Google Scholar 

  • Vivekananthan DP, Penn MS, Sapp SK, Hsu A, Topol EJ (2003) Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet 361:2017–2023

    CAS  PubMed  Google Scholar 

  • Voinea M, Georgescu A, Manea A, Dragomir E, Manduteanu I, Popov D, Simionescu M (2004) Superoxide dismutase entrapped-liposomes restore the impaired endothelium-dependent relaxation of resistance arteries in experimental diabetes. Eur J Pharmacol 484:111–118

    CAS  PubMed  Google Scholar 

  • Wakabayashi N, Dinkova-Kostova AT, Holtzclaw WD, Kang MI, Kobayashi A, Yamamoto M, Kensler TW, Talalay P (2004) Protection against electrophile and oxidant stress by induction of the phase 2 response: fate of cysteines of the Keap1 sensor modified by inducers. Proc Natl Acad Sci USA 101:2040–2045

    CAS  PubMed Central  PubMed  Google Scholar 

  • Walsh SK, English FA, Crocker IP, Johns EJ, Kenny LC (2012) Contribution of PARP to endothelial dysfunction and hypertension in a rat model of pre-eclampsia. Br J Pharmacol 166:2109–2116

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wang X, Tao L, Hai CX (2012) Redox-regulating role of insulin: the essence of insulin effect. Mol Cell Endocrinol 349:111–127

    CAS  PubMed  Google Scholar 

  • Wild S, Roglic G, Green A, Sicree R, King H (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27:1047–1053

    PubMed  Google Scholar 

  • Xiao Y, Xu A, Law LS, Chen C, Li H, Li X, Yang L, Liu S, Zhou Z, Lam KS (2012) Distinct changes in serum fibroblast growth factor 21 levels in different subtypes of diabetes. J Clin Endocrinol Metab 97:E54–E58

    CAS  PubMed  Google Scholar 

  • Yamagishi S, Matsui T (2011) Nitric oxide, a janus-faced therapeutic target for diabetic microangiopathy-friend or foe? Pharmacol Res 64:187–194

    CAS  PubMed  Google Scholar 

  • Yamashita N, Hoshida S, Otsu K, Asahi M, Kuzuya T, Hori M (1999) Exercise provides direct biphasic cardioprotection via manganese superoxide dismutase activation. J Exp Med 189:1699–1706

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zeller M, Korandji C, Guilland JC, Sicard P, Vergely C, Lorgis L, Beer JC, Duvillard L, Lagrost AC, Moreau D, Gambert P, Cottin Y, Rochette L (2008) Impact of asymmetric dimethylarginine on mortality after acute myocardial infarction. Arterioscler Thromb Vasc Biol 28:954–960

    CAS  PubMed  Google Scholar 

  • Zhou YH, Tang JY, Wu MJ, Lu J, Wei X, Qin YY, Wang C, Xu JF, He J (2011) Effect of folic acid supplementation on cardiovascular outcomes: a systematic review and meta-analysis. PLoS One 6:e25142

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ziegler D, Low PA, Litchy WJ, Boulton AJ, Vinik AI, Freeman R, Samigullin R, Tritschler H, Munzel U, Maus J, Schutte K, Dyck PJ (2011) Efficacy and safety of antioxidant treatment with alpha-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. Diabetes Care 34:2054–2060

    CAS  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratoire de Physiopathologie et Pharmacologie Cardio-Métaboliques (LPPCM), INSERM UMR866, Facultés de Médecine et Pharmacie, Université de Bourgogne, 7 Boulevard Jeanne d’Arc, 21000, Cedex, Dijon, France

    Luc Rochette & Catherine Vergely

Authors
  1. Luc Rochette
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Catherine Vergely
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Luc Rochette .

Editor information

Editors and Affiliations

  1. Department of Pharmacology and Therapeutics, University of British Colombia, Vancouver, British Columbia, Canada

    Ismail Laher

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Berlin Heidelberg

About this entry

Cite this entry

Rochette, L., Vergely, C. (2014). Antioxidants and Diabetes. In: Laher, I. (eds) Systems Biology of Free Radicals and Antioxidants. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30018-9_156

Download citation

Publish with us

Policies and ethics

Search

Navigation