Please wait a minute...

Frontiers of Medicine

Front. Med.    2020, Vol. 14 Issue (5) : 583-600
Oxidative stress and diabetes: antioxidative strategies
Pengju Zhang1, Tao Li1, Xingyun Wu1, Edouard C. Nice2, Canhua Huang1(), Yuanyuan Zhang1()
1. Department of Pharmacology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China
2. Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
Download: PDF(1404 KB)   HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks

Diabetes mellitus is one of the major public health problems worldwide. Considerable recent evidence suggests that the cellular reduction–oxidation (redox) imbalance leads to oxidative stress and subsequent occurrence and development of diabetes and related complications by regulating certain signaling pathways involved in β-cell dysfunction and insulin resistance. Reactive oxide species (ROS) can also directly oxidize certain proteins (defined as redox modification) involved in the diabetes process. There are a number of potential problems in the clinical application of antioxidant therapies including poor solubility, storage instability and non-selectivity of antioxidants. Novel antioxidant delivery systems may overcome pharmacokinetic and stability problem and improve the selectivity of scavenging ROS. We have therefore focused on the role of oxidative stress and antioxidative therapies in the pathogenesis of diabetes mellitus. Precise therapeutic interventions against ROS and downstream targets are now possible and provide important new insights into the treatment of diabetes.

Keywords diabetes      oxidative stress      redox modification      antioxidative therapy      novel antioxidant delivery     
Corresponding Author(s): Canhua Huang,Yuanyuan Zhang   
Just Accepted Date: 30 December 2019   Online First Date: 07 April 2020    Issue Date: 12 October 2020
 Cite this article:   
Pengju Zhang,Tao Li,Xingyun Wu, et al. Oxidative stress and diabetes: antioxidative strategies[J]. Front. Med., 2020, 14(5): 583-600.
E-mail this article
E-mail Alert
Articles by authors
Pengju Zhang
Tao Li
Xingyun Wu
Edouard C. Nice
Canhua Huang
Yuanyuan Zhang
Fig.1  The sources of ROS/RNS and their harmful effects. ROS/RNS arise from mitochondrial electron transport chain or/and non-mitochondrial pathways. When cells and tissues are exposed to hypoxia, inflammation and immune response, particularly hyperglycemia, and high free fatty acids, the generation of ROS/RNS will be elevated. The overproduction of ROS/RNS leads to oxidative stress that regulates important cell signaling pathways which govern cell proliferation, inflammation, and cell survival. Abbreviations: NOX, nicotinamide adenine nucleotide phosphate oxidase; NADPH, nicotinamide adenine nucleotide phosphate; O2•−, superoxide; HO, hemeoxygenase; XO, xanthine oxidase; COX, cyclooxygenases; iNOS, inducible NOS; eNOS, endothelial NOS; NOS, nitric oxide synthase; ONOO, peroxynitrite; NO, nitric oxide; ETC, electron transport chain; CI, complex 1; MAO, monoamine oxidase; α-GD, α-glycerophosphate dehydrogenase; H2O2, hydrogen peroxide; ROS, reactive oxygen species; RNS, reactive nitrogen species; JNK, c-jun N-terminal kinase; PKC, protein kinase C; IKKβ, IκB kinase β; PI3K, phosphatidylinositide 3-kinase; PARP-1, poly (ADP-ribose) polymerases; NF-kB, nuclear transcription factor κB; Nrf2, nuclear factor E2-ralated factor 2; FOXO, forkhead box protein O.
Major antioxidants Main functions References
Enzymatic antioxidants
?SOD Catalyzes 2O2•− + 2H+⇄ O2 + H2O2 [66]
?CAT Catalyzes 2H2O2→ O2 + H2O [67]
?GPx Catalyzes the breakdown of H2O2 and lipid hydroperoxides to H2O and lipid alcohols [68]
Vitaminic antioxidants
?Vitamin C Scavenges free radicals [69]
?Vitamin E Scavenges lipid peroxide radicals in membranes [71]
?Vitamin D Modulates the expression of antioxidants [155]
?Vitamin B9 Inhibits NOX4/Vav2/NLRP3 signaling [156]
Other antioxidants
?GSH Scavenges free radicals [157]
?CoQ10 Improves mitochondrial dysfunction [158]
?NAC Reduces glutathione [159]
?LA Cofactor for pyruvate dehydrogenase complex [160]
?Trace elements Involves in redox cycling reactions [27]
Tab.1  Antioxidants
Fig.2  Oxidative stress and pancreatic β-cell dysfunction. Oxidative stress mainly influences β-cell function from two perspectives: reducing insulin secretion and promoting β-cell apoptosis. On the one hand, ROS overproduction suppresses insulin production and secretion by opening ATP-sensitive K+ channels and inhibiting insulin genes transcription. On the other hand, oxidative stress induces β-cell apoptosis by activating p21, JNK, p38 MAPK, and NF-kB. Abbreviations: NOX4, nicotinamide adenine nucleotide phosphate oxidase; KATP, ATP-sensitive K+ channels; VGCC, voltage-gated calcium channels; p21, a cyclin-dependent kinase inhibitor; JNK, c-jun N-terminal kinase; p38 MAPK, p38 AMP-activated protein kinase; NF-kB, nuclear transcription factor κB; FOXO1, forkhead box protein O 1; PDX1, pancreas duodenal homeobox factor 1; MaFA, musculoaponeurotic fibrosarcoma protein A; INS, insulin genes.
Fig.3  Oxidative stress and insulin resistance in skeletal cells. Glucose traverses the membrane of muscle cells by a facilitative diffusion process which relies on the GLUT4 glucose transporter translocation from intracellular storage depots to the sarcolemmal membrane and T-tubules upon muscle contraction. The GLUT4 translocation is modulated by insulin through the activation of a complex cascade of signaling events. Under oxidative stress due to sustained hyperglycemia, elevated FFA inhibits glucose transportation by impairing insulin signals. ROS decreases insulin sensitivity by activating casein kinase-2 (CK2) which promotes the translocation of GLUT4 to lysosomes rather than the sarcolemmal membrane. Abbreviations: NOX, nicotinamide adenine nucleotide phosphate oxidase; IR, insulin receptor; IRS-1/2, insulin receptor substrates-1/2; H2O2, hydrogen peroxide; O2•− , superoxide; ROS, reactive oxygen species; JNK, c-jun N-terminal kinase; IKKβ, IκB kinase β; CK2, casein kinase-2; GLUT4, glucose transporter 4; PI3K, phosphatidylinositide 3-kinase; PIP2, phosphatidylinositol 4,5-bisphosphate; PIP3, phosphatidylinositol-3,4,5-triphosphate; PDK1, 3-phosphoinositide-dependent kinase; mTOR2, mechanistic target of rapamycin 2; TBC1D1/2, Tre-2/BUB2/cdc 1 domain family 1/2.
Fig.4  Oxidative stress and vascular endothelial dysfunction. There are four major mechanisms associated with vascular endothelial cell dysfunction, including the PKC, AGEs/RAGE, polyol and hexosamine pathways. The PKC and hexosamine pathways diminish the generation of NO which is a critical regulatory factor to normalize vascular function. The polyol and AGEs/RAGE pathways elevate the levels of ROS in endothelia cells and then activate NF-kB which induces the inflammation and thrombosis of vascular endothelia by enhancing several genes expression including VEGF, VCAM-1 and ET-1. Abbreviations: eNOS, endothelial nitric oxide synthase; O-GLcNAC, O-N-acetylglucosamine; NO, nitric oxide; PKC, protein kinase C; ROS, reactive oxygen species; AGE, advanced glycosylation end products; RAGE, receptor for advanced glycosylation end products; UDP-GlcNAc, uridine diphosphate N-acetylglucosamine; G-6-P, glucose 6 phosphate; F-6-P, fructose 6 phosphate; DAG, diacylglycerol; GFAT, glutamine fructose-6-phosphate aminotransferase; GADPH, D-glyceraldehyde-3-phosphate dehydrogenase; GSH, glutathione; NF-kB, nuclear transcription factor κB; VEGF, vascular endothelial growth factor; VCAM-1, vascular adhesion molecular-1; ET-1, endothelin-1.
Fig.5  Patterns of redox protein modification. The highly reactive thiol groups of proteins are easily oxidized to sulfenic acid (RSOH) by ROS, or are oxidized to S-nitrosylation in response to RNS. Sulfenic acid (RSOH) has the capacity to react with nearby thiols to form intramolecular or intermolecular disulfide bonds due to its highly reactive nature. Sulfenic acid (RSOH) can also react with GSH to generate S-glutathiolation. These redox proteins modifications are reversible and these reaction products can be restored into free thiols by cellular reductants. However, sulfenic acid (RSOH) can also be further oxidized to irreversible products (including RSO2H and RSO3H). Abbreviations: ROS, reactive oxygen species; RNS, reactive nitrogen species; GSH, glutathione.
Antioxidative strategies Main functions References
Lifestyle interventions
?Exercise Increases muscle mitochondrial oxidative capacity and enhances NO bioavailability [161]
?Dietary Decreases uptake of free fatty acids [142]
?Microparticle Promotes the entry of antioxidants with poor membrane permeability [143]
?Nanoparticle Increases the bioavailability of antioxidants [144]
?Liposome Improves antioxidative capacity of antioxidants [145]
Agents targeting ROS sources
?MitoQ-TPP Prevents mitochondrial oxidative damage [162]
?TEMPOL Prevents mitochondrial oxidative damage and improves tissue oxygenation [163]
?GKT137831 Inhibits the activation of caspase-3 and cell death resulted from high glucose [148]
Agents targetingredox modification
?Bardoxolone methyl Regulates the Nrf2/Keap1/ARE pathway through Keap1 post-translational modification [150]
?tBHQ Regulates the Nrf2/Keap1/ARE pathway through Keap1 post-translational modification [151]
?Selenocompounds Modifies PKC C-terminal catalytic domain and inhibits cellular PKC activity [152]
Tab.2  Therapeutic antioxidative strategies for diabetes
1 JM Evans, RW Newton, DA Ruta, TM MacDonald, AD Morris. Socio-economic status, obesity and prevalence of type 1 and type 2 diabetes mellitus. Diabet Med 2000; 17(6): 478–480 pmid: 10975218
2 G Bruno, C Runzo, P Cavallo-Perin, F Merletti, M Rivetti, S Pinach, G Novelli, M Trovati, F Cerutti, G Pagano; Piedmont Study Group for Diabetes Epidemiology. Incidence of type 1 and type 2 diabetes in adults aged 30–49 years: the population-based registry in the Province of Turin, Italy. Diabetes Care 2005; 28(11): 2613–2619 pmid: 16249528
3 N Holman, B Young, R Gadsby. Current prevalence of type 1 and type 2 diabetes in adults and children in the UK. Diabet Med 2015; 32(9): 1119–1120 pmid: 25962518
4 Y Yang, L Chan. Monogenic diabetes: what it teaches us on the common forms of type 1 and type 2 diabetes. Endocr Rev 2016; 37(3): 190–222 pmid: 27035557
5 B Matkovics, SI Varga, L Szabó, H Witas. The effect of diabetes on the activities of the peroxide metabolism enzymes. Horm Metab Res 1982; 14(2): 77–79 pmid: 7068100
6 R Paoletti, C Bolego, A Poli, A Cignarella. Metabolic syndrome, inflammation and atherosclerosis. Vasc Health Risk Manag 2006; 2(2): 145–152 pmid: 17319458
7 SA Bukhari, SA Naqvi, SA Nagra, F Anjum, S Javed, M Farooq. Assessing of oxidative stress related parameters in diabetes mellitus type 2: cause excessive damaging to DNA and enhanced homocysteine in diabetic patients. Pak J Pharm Sci 2015; 28(2): 483–491
pmid: 25730782
8 JL Evans, ID Goldfine, BA Maddux, GM Grodsky. Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr Rev 2002; 23(5): 599–622 pmid: 12372842
9 JA David, WJ Rifkin, PS Rabbani, DJ Ceradini. The Nrf2/Keap1/ARE pathway and oxidative stress as a therapeutic target in type II diabetes mellitus. J Diabetes Res 2017; 2017: 4826724 pmid: 28913364
10 EN Okatan, E Tuncay, B Turan. Cardioprotective effect of selenium via modulation of cardiac ryanodine receptor calcium release channels in diabetic rat cardiomyocytes through thioredoxin system. J Nutr Biochem 2013; 24(12): 2110–2118 pmid: 24183307
11 LS Duvvuri, S Katiyar, A Kumar, W Khan. Delivery aspects of antioxidants in diabetes management. Expert Opin Drug Deliv 2015; 12(5): 827–844 pmid: 25582375
12 AC Maritim, RA Sanders, JB Watkins 3rd. Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol 2003; 17(1): 24–38 pmid: 12616644
13 NA Calcutt, VL Lopez, AD Bautista, LM Mizisin, BR Torres, AL Shroads, AP Mizisin, PW Stacpoole. Peripheral neuropathy in rats exposed to dichloroacetate. J Neuropathol Exp Neurol 2009; 68(9): 985–993 pmid: 19680144
14 SP Gray, K Jandeleit-Dahm. The pathobiology of diabetic vascular complications—cardiovascular and kidney disease. J Mol Med (Berl) 2014; 92(5): 441–452 pmid: 24687627
15 SE Heinonen, G Genové, E Bengtsson, T Hübschle, L Åkesson, K Hiss, A Benardeau, S Ylä-Herttuala, AC Jönsson-Rylander, MF Gomez. Animal models of diabetic macrovascular complications: key players in the development of new therapeutic approaches. J Diabetes Res 2015; 2015: 404085 pmid: 25785279
16 Z Gong, ML Neuhouser, PJ Goodman, D Albanes, C Chi, AW Hsing, SM Lippman, EA Platz, MN Pollak, IM Thompson, AR Kristal. Obesity, diabetes, and risk of prostate cancer: results from the prostate cancer prevention trial. Cancer Epidemiol Biomarkers Prev 2006; 15(10): 1977–1983 pmid: 17035408
17 FP Lu, KP Lin, HK Kuo. Diabetes and the risk of multi-system aging phenotypes: a systematic review and meta-analysis. PLoS One 2009; 4(1): e4144 pmid: 19127292
18 E Wong, K Backholer, E Gearon, J Harding, R Freak-Poli, C Stevenson, A Peeters. Diabetes and risk of physical disability in adults: a systematic review and meta-analysis. Lancet Diabetes Endocrinol 2013; 1(2): 106–114 pmid: 24622316
19 CY Jeon, MB Murray. Diabetes mellitus increases the risk of active tuberculosis: a systematic review of 13 observational studies. PLoS Med 2008; 5(7): e152 pmid: 18630984
20 AL Riza, F Pearson, C Ugarte-Gil, B Alisjahbana, S van de Vijver, NM Panduru, PC Hill, R Ruslami, D Moore, R Aarnoutse, JA Critchley, R van Crevel. Clinical management of concurrent diabetes and tuberculosis and the implications for patient services. Lancet Diabetes Endocrinol 2014; 2(9): 740–753 pmid: 25194887
21 T Roy, CE Lloyd. Epidemiology of depression and diabetes: a systematic review. J Affect Disord 2012; 142(Suppl): S8–S21 pmid: 23062861
22 WP You, M Henneberg. Type 1 diabetes prevalence increasing globally and regionally: the role of natural selection and life expectancy at birth. BMJ Open Diabetes Res Care 2016; 4(1): e000161 pmid: 26977306
23 JA Bluestone, K Herold, G Eisenbarth. Genetics, pathogenesis and clinical interventions in type 1 diabetes. Nature 2010; 464(7293): 1293–1300 pmid: 20432533
24 A Katsarou, S Gudbjörnsdottir, A Rawshani, D Dabelea, E Bonifacio, BJ Anderson, LM Jacobsen, DA Schatz, Å Lernmark. Type 1 diabetes mellitus. Nat Rev Dis Primers 2017; 3(1): 17016 pmid: 28358037
25 R Barnett. Type 1 diabetes. Lancet 2018; 391(10117): 195 pmid: 30277879
26 T Sakurai, S Tsuchiya. Superoxide production from nonenzymatically glycated protein. FEBS Lett 1988; 236(2): 406–410 pmid: 2842191
27 L Rochette, M Zeller, Y Cottin, C Vergely. Diabetes, oxidative stress and therapeutic strategies. Biochim Biophys Acta 2014; 1840(9): 2709–2729 pmid: 24905298
28 M Zeller, PG Steg, J Ravisy, L Lorgis, Y Laurent, P Sicard, L Janin-Manificat, JC Beer, H Makki, AC Lagrost, L Rochette, Y Cottin; RICO Survey Working Group. Relation between body mass index, waist circumference, and death after acute myocardial infarction. Circulation 2008; 118(5): 482–490 pmid: 18625893
29 AH Olsson, T Rönn, T Elgzyri, O Hansson, KF Eriksson, L Groop, A Vaag, P Poulsen, C Ling. The expression of myosin heavy chain (MHC) genes in human skeletal muscle is related to metabolic characteristics involved in the pathogenesis of type 2 diabetes. Mol Genet Metab 2011; 103(3): 275–281 pmid: 21470888
30 CR Kahn. Banting Lecture. Insulin action, diabetogenes, and the cause of type II diabetes. Diabetes 1994; 43(8): 1066–1084 pmid: 8039601
31 OR Ayepola, NL Brooks, O Oguntibeju. Oxidative stress and diabetic complications: the role of antioxidant vitamins and flavonoids. In: Oguntibeju O. Antioxidant-Antidiabetic Agents and Human Health. IntechOpen, 2014
32 LS Fetita, E Sobngwi, P Serradas, F Calvo, JF Gautier. Consequences of fetal exposure to maternal diabetes in offspring. J Clin Endocrinol Metab 2006; 91(10): 3718–3724 pmid: 16849402
33 L Bellamy, JP Casas, AD Hingorani, D Williams. Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet 2009; 373(9677): 1773–1779 pmid: 19465232
34 PM Catalano, HD McIntyre, JK Cruickshank, DR McCance, AR Dyer, BE Metzger, LP Lowe, ER Trimble, DR Coustan, DR Hadden, B Persson, M Hod, JJ Oats; HAPO Study Cooperative Research Group. The hyperglycemia and adverse pregnancy outcome study: associations of GDM and obesity with pregnancy outcomes. Diabetes Care 2012; 35(4): 780–786 pmid: 22357187
35 L Kelstrup, P Damm, ER Mathiesen, T Hansen, AA Vaag, O Pedersen, TD Clausen. Insulin resistance and impaired pancreatic β-cell function in adult offspring of women with diabetes in pregnancy. J Clin Endocrinol Metab 2013; 98(9): 3793–3801 pmid: 23796568
36 World Health Organization. WHO Guidelines Approved by the Guidelines Review Committee. In: Diagnostic Criteria and Classification of Hyperglycaemia First Detected in Pregnancy. Geneva: World Health Organization, 2013
37 T Radaelli, A Varastehpour, P Catalano, S Hauguel-de Mouzon. Gestational diabetes induces placental genes for chronic stress and inflammatory pathways. Diabetes 2003; 52(12): 2951–2958 pmid: 14633856
38 I Mrizak, O Grissa, B Henault, M Fekih, A Bouslema, I Boumaiza, M Zaouali, Z Tabka, NA Khan. Placental infiltration of inflammatory markers in gestational diabetic women. Gen Physiol Biophys 2014; 33(2): 169–176 pmid: 24595845
39 A Ceriello, E Motz. Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arterioscler Thromb Vasc Biol 2004; 24(5): 816–823 pmid: 14976002
40 L Mohsen, DM Akmal, EKE Ghonaim, NM Riad. Role of mean platelet volume and ischemia modified albumin in evaluation of oxidative stress and its association with postnatal complications in infants of diabetic mothers. J Matern Fetal Neonatal Med 2018; 31(14): 1819–1823 pmid: 28502205
41 JM Forbes, MT Coughlan, ME Cooper. Oxidative stress as a major culprit in kidney disease in diabetes. Diabetes 2008; 57(6): 1446–1454 pmid: 18511445
42 M Valko, D Leibfritz, J Moncol, MT Cronin, M Mazur, J Telser. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007; 39(1): 44–84 pmid: 16978905
43 S Abhary, N Kasmeridis, KP Burdon, A Kuot, MJ Whiting, WP Yew, N Petrovsky, JE Craig. Diabetic retinopathy is associated with elevated serum asymmetric and symmetric dimethylarginines. Diabetes Care 2009; 32(11): 2084–2086 pmid: 19675197
44 J Cassuto, H Dou, I Czikora, A Szabo, VS Patel, V Kamath, E Belin de Chantemele, A Feher, MJ Romero, Z Bagi. Peroxynitrite disrupts endothelial caveolae leading to eNOS uncoupling and diminished flow-mediated dilation in coronary arterioles of diabetic patients. Diabetes 2014; 63(4): 1381–1393 pmid: 24353182
45 MC Franco, Y Ye, CA Refakis, JL Feldman, AL Stokes, M Basso, RM Melero Fernández de Mera, NA Sparrow, NY Calingasan, M Kiaei, TW Rhoads, TC Ma, M Grumet, S Barnes, MF Beal, JS Beckman, R Mehl, AG Estévez. Nitration of Hsp90 induces cell death. Proc Natl Acad Sci USA 2013; 110(12): E1102–E1111 pmid: 23487751
46 GS Shadel, TL Horvath. Mitochondrial ROS signaling in organismal homeostasis. Cell 2015; 163(3): 560–569 pmid: 26496603
47 B Ekstedt. Substrate specificity of the different forms of monoamine oxidase in rat liver mitochondria. Biochem Pharmacol 1976; 25(10): 1133–1138 pmid: 938537
48 F Orsini, E Migliaccio, M Moroni, C Contursi, VA Raker, D Piccini, I Martin-Padura, G Pelliccia, M Trinei, M Bono, C Puri, C Tacchetti, M Ferrini, R Mannucci, I Nicoletti, L Lanfrancone, M Giorgio, PG Pelicci. The life span determinant p66Shc localizes to mitochondria where it associates with mitochondrial heat shock protein 70 and regulates trans-membrane potential. J Biol Chem 2004; 279(24): 25689–25695 pmid: 15078873
49 T Mráček, A Pecinová, M Vrbacký, Z Drahota, J Houstek. High efficiency of ROS production by glycerophosphate dehydrogenase in mammalian mitochondria. Arch Biochem Biophys 2009; 481(1): 30–36 pmid: 18952046
50 A Boveris, N Oshino, B Chance. The cellular production of hydrogen peroxide. Biochem J 1972; 128(3): 617–630
pmid: 4404507
51 PR Gardner, I Fridovich. Inactivation-reactivation of aconitase in Escherichia coli. a sensitive measure of superoxide radical. J Biol Chem 1992; 267(13): 8757–8763
pmid: 1315737
52 J Rivera, CG Sobey, AK Walduck, GR Drummond. Nox isoforms in vascular pathophysiology: insights from transgenic and knockout mouse models. Redox Rep 2010; 15(2): 50–63 pmid: 20500986
53 Y Kayama, U Raaz, A Jagger, M Adam, IN Schellinger, M Sakamoto, H Suzuki, K Toyama, JM Spin, PS Tsao. Diabetic cardiovascular disease induced by oxidative stress. Int J Mol Sci 2015; 16(10): 25234–25263 pmid: 26512646
54 T Kietzmann, A Petry, A Shvetsova, JM Gerhold, A Görlach. The epigenetic landscape related to reactive oxygen species formation in the cardiovascular system. Br J Pharmacol 2017; 174(12): 1533–1554 pmid: 28332701
55 R Butler, AD Morris, JJ Belch, A Hill, AD Struthers. Allopurinol normalizes endothelial dysfunction in type 2 diabetics with mild hypertension. Hypertension 2000; 35(3): 746–751 pmid: 10720589
56 RP Brandes, N Weissmann, K Schröder. Redox-mediated signal transduction by cardiovascular Nox NADPH oxidases. J Mol Cell Cardiol 2014; 73: 70–79 pmid: 24560815
57 C Baum, SS Johannsen, T Zeller, D Atzler, FM Ojeda, PS Wild, CR Sinning, KJ Lackner, T Gori, E Schwedhelm, RH Böger, S Blankenberg, T Münzel, RB Schnabel; Gutenberg Health Study investigators. ADMA and arginine derivatives in relation to non-invasive vascular function in the general population. Atherosclerosis 2016; 244: 149–156 pmid: 26638011
58 GR Drummond, S Selemidis, KK Griendling, CG Sobey. Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets. Nat Rev Drug Discov 2011; 10(6): 453–471 pmid: 21629295
59 KK Griendling, D Sorescu, M Ushio-Fukai. NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res 2000; 86(5): 494–501 pmid: 10720409
60 SP Gray, E Di Marco, J Okabe, C Szyndralewiez, F Heitz, AC Montezano, JB de Haan, C Koulis, A El-Osta, KL Andrews, JP Chin-Dusting, RM Touyz, K Wingler, ME Cooper, HH Schmidt, KA Jandeleit-Dahm. NADPH oxidase 1 plays a key role in diabetes mellitus-accelerated atherosclerosis. Circulation 2013; 127(18): 1888–1902 pmid: 23564668
61 PL Huang, Z Huang, H Mashimo, KD Bloch, MA Moskowitz, JA Bevan, MC Fishman. Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature 1995; 377(6546): 239–242 pmid: 7545787
62 J Tejero, S Shiva, MT Gladwin. Sources of vascular nitric oxide and reactive oxygen species and their regulation. Physiol Rev 2019; 99(1): 311–379 pmid: 30379623
63 A Engineer, T Saiyin, ER Greco, Q Feng. Say NO to ROS: their roles in embryonic heart development and pathogenesis of congenital heart defects in maternal diabetes. Antioxidants 2019; 8(10): E436 pmid: 31581464
64 E Rozoy, S Simard, Y Liu, D Kitts, J Lessard, L Bazinet. The use of cyclic voltammetry to study the oxidation of l-5-methyltetrahydrofolate and its preservation by ascorbic acid. Food Chem 2012; 132(3): 1429–1435 pmid: 29243632
65 L Bazinet, A Doyen. Antioxidants, mechanisms, and recovery by membrane processes. Crit Rev Food Sci Nutr 2017; 57(4): 677–700 pmid: 25674704
66 AE Butler, J Janson, S Bonner-Weir, R Ritzel, RA Rizza, PC Butler. β-cell deficit and increased β-cell apoptosis in humans with type 2 diabetes. Diabetes 2003; 52(1): 102–110 pmid: 12502499
67 G Marrazzo, I Barbagallo, F Galvano, M Malaguarnera, D Gazzolo, A Frigiola, N D’Orazio, G Li Volti. Role of dietary and endogenous antioxidants in diabetes. Crit Rev Food Sci Nutr 2014; 54(12): 1599–1616 pmid: 24580561
68 M Banerjee, P Vats. Reactive metabolites and antioxidant gene polymorphisms in type 2 diabetes mellitus. Redox Biol 2014; 2: 170–177 pmid: 25460725
69 J Lykkesfeldt, AJ Michels, B Frei. Vitamin C. Adv Nutr 2014; 5(1): 16–18 pmid: 24425716
70 S López-Burillo, DX Tan, JC Mayo, RM Sainz, LC Manchester, RJ Reiter. Melatonin, xanthurenic acid, resveratrol, EGCG, vitamin C and α-lipoic acid differentially reduce oxidative DNA damage induced by Fenton reagents: a study of their individual and synergistic actions. J Pineal Res 2003; 34(4): 269–277 pmid: 12662349
71 Q Jiang. Natural forms of vitamin E: metabolism, antioxidant, and anti-inflammatory activities and their role in disease prevention and therapy. Free Radic Biol Med 2014; 72: 76–90 pmid: 24704972
72 MA Farhangi, M Mesgari-Abbasi, G Hajiluian, G Nameni, P Shahabi. Adipose tissue inflammation and oxidative stress: the ameliorative effects of vitamin D. Inflammation 2017; 40(5): 1688–1697 pmid: 28674792
73 PA Gerber, GA Rutter. The role of oxidative stress and hypoxia in pancreatic β-cell dysfunction in diabetes mellitus. Antioxid Redox Signal 2017; 26(10): 501–518 pmid: 27225690
74 G Drews, P Krippeit-Drews, M Düfer. Oxidative stress and β-cell dysfunction. Pflugers Arch 2010; 460(4): 703–718 pmid: 20652307
75 P Maechler, L Jornot, CB Wollheim. Hydrogen peroxide alters mitochondrial activation and insulin secretion in pancreatic β cells. J Biol Chem 1999; 274(39): 27905–27913 pmid: 10488138
76 RP Robertson, J Harmon, PO Tran, V Poitout. β-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes. Diabetes 2004; 53(Suppl 1): S119–S124 pmid: 14749276
77 N Lameloise, P Muzzin, M Prentki, F Assimacopoulos-Jeannet. Uncoupling protein 2: a possible link between fatty acid excess and impaired glucose-induced insulin secretion? Diabetes 2001; 50(4): 803–809 pmid: 11289045
78 H Kaneto, G Xu, N Fujii, S Kim, S Bonner-Weir, GC Weir. Involvement of c-Jun N-terminal kinase in oxidative stress-mediated suppression of insulin gene expression. J Biol Chem 2002; 277(33): 30010–30018 pmid: 12011047
79 D Kawamori, Y Kajimoto, H Kaneto, Y Umayahara, Y Fujitani, T Miyatsuka, H Watada, IB Leibiger, Y Yamasaki, M Hori. Oxidative stress induces nucleo-cytoplasmic translocation of pancreatic transcription factor PDX-1 through activation of c-Jun NH(2)-terminal kinase. Diabetes 2003; 52(12): 2896–2904 pmid: 14633849
80 D Kawamori, H Kaneto, Y Nakatani, TA Matsuoka, M Matsuhisa, M Hori, Y Yamasaki. The forkhead transcription factor Foxo1 bridges the JNK pathway and the transcription factor PDX-1 through its intracellular translocation. J Biol Chem 2006; 281(2): 1091–1098 pmid: 16282329
81 TA Matsuoka, I Artner, E Henderson, A Means, M Sander, R Stein. The MafA transcription factor appears to be responsible for tissue-specific expression of insulin. Proc Natl Acad Sci USA 2004; 101(9): 2930–2933 pmid: 14973194
82 I El Khattabi, A Sharma. Preventing p38 MAPK-mediated MafA degradation ameliorates β-cell dysfunction under oxidative stress. Mol Endocrinol 2013; 27(7): 1078–1090 pmid: 23660596
83 T Kondo, I El Khattabi, W Nishimura, DR Laybutt, P Geraldes, S Shah, G King, S Bonner-Weir, G Weir, A Sharma. p38 MAPK is a major regulator of MafA protein stability under oxidative stress. Mol Endocrinol 2009; 23(8): 1281–1290 pmid: 19407223
84 EN Gurzov, DL Eizirik. Bcl-2 proteins in diabetes: mitochondrial pathways of β-cell death and dysfunction. Trends Cell Biol 2011; 21(7): 424–431 pmid: 21481590
85 H Heimberg, Y Heremans, C Jobin, R Leemans, AK Cardozo, M Darville, DL Eizirik. Inhibition of cytokine-induced NF-κB activation by adenovirus-mediated expression of a NF-κB super-repressor prevents β-cell apoptosis. Diabetes 2001; 50(10): 2219–2224 pmid: 11574401
86 EJ Henriksen, MK Diamond-Stanic, EM Marchionne. Oxidative stress and the etiology of insulin resistance and type 2 diabetes. Free Radic Biol Med 2011; 51(5): 993–999 pmid: 21163347
87 K Mahadev, H Motoshima, X Wu, JM Ruddy, RS Arnold, G Cheng, JD Lambeth, BJ Goldstein. The NAD(P)H oxidase homolog Nox4 modulates insulin-stimulated generation of H2O2 and plays an integral role in insulin signal transduction. Mol Cell Biol 2004; 24(5): 1844–1854 pmid: 14966267
88 TL Archuleta, AM Lemieux, V Saengsirisuwan, MK Teachey, KA Lindborg, JS Kim, EJ Henriksen. Oxidant stress-induced loss of IRS-1 and IRS-2 proteins in rat skeletal muscle: role of p38 MAPK. Free Radic Biol Med 2009; 47(10): 1486–1493 pmid: 19703555
89 CA Stuart, ME Howell, BM Cartwright, MP McCurry, ML Lee, MW Ramsey, MH Stone. Insulin resistance and muscle insulin receptor substrate-1 serine hyperphosphorylation. Physiol Rep 2014; 2(12): e12236 pmid: 25472611
90 GS Hotamisligil, P Peraldi, A Budavari, R Ellis, MF White, BM Spiegelman. IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-α- and obesity-induced insulin resistance. Science 1996; 271(5249): 665–668 pmid: 8571133
91 J Hirosumi, G Tuncman, L Chang, CZ Görgün, KT Uysal, K Maeda, M Karin, GS Hotamisligil. A central role for JNK in obesity and insulin resistance. Nature 2002; 420(6913): 333–336 pmid: 12447443
92 M Yuan, N Konstantopoulos, J Lee, L Hansen, ZW Li, M Karin, SE Shoelson. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of IKKβ. Science 2001; 293(5535): 1673–1677 pmid: 11533494
93 MK Diamond-Stanic, EJ Henriksen. Direct inhibition by angiotensin II of insulin-dependent glucose transport activity in mammalian skeletal muscle involves a ROS-dependent mechanism. Arch Physiol Biochem 2010; 116(2): 88–95 pmid: 20384568
94 S Hurrle, WH Hsu. The etiology of oxidative stress in insulin resistance. Biomed J 2017; 40(5): 257–262 pmid: 29179880
95 E Rurali, M Noris, A Chianca, R Donadelli, F Banterla, M Galbusera, G Gherardi, S Gastoldi, A Parvanova, I Iliev, A Bossi, C Haefliger, R Trevisan, G Remuzzi, P Ruggenenti; BENEDICT Study Group. ADAMTS13 predicts renal and cardiovascular events in type 2 diabetic patients and response to therapy. Diabetes 2013; 62(10): 3599–3609 pmid: 23733198
96 N Kaiser, S Sasson, EP Feener, N Boukobza-Vardi, S Higashi, DE Moller, S Davidheiser, RJ Przybylski, GL King. Differential regulation of glucose transport and transporters by glucose in vascular endothelial and smooth muscle cells. Diabetes 1993; 42(1): 80–89 pmid: 7678404
97 NR Nascimento, LM Lessa, MR Kerntopf, CM Sousa, RS Alves, MG Queiroz, J Price, DB Heimark, J Larner, X Du, M Brownlee, A Gow, C Davis, MC Fonteles. Inositols prevent and reverse endothelial dysfunction in diabetic rat and rabbit vasculature metabolically and by scavenging superoxide. Proc Natl Acad Sci USA 2006; 103(1): 218–223 pmid: 16373499
98 F Giacco, M Brownlee. Oxidative stress and diabetic complications. Circ Res 2010; 107(9): 1058–1070 pmid: 21030723
99 JL Wautier, AM Schmidt. Protein glycation: a firm link to endothelial cell dysfunction. Circ Res 2004; 95(3): 233–238 pmid: 15297385
100 PJ White, M Arita, R Taguchi, JX Kang, A Marette. Transgenic restoration of long-chain n-3 fatty acids in insulin target tissues improves resolution capacity and alleviates obesity-linked inflammation and insulin resistance in high-fat-fed mice. Diabetes 2010; 59(12): 3066–3073 pmid: 20841610
101 C Giannini, A Mohn, F Chiarelli, CJ Kelnar. Macrovascular angiopathy in children and adolescents with type 1 diabetes. Diabetes Metab Res Rev 2011; 27(5): 436–460 pmid: 21433262
102 MA Gimbrone Jr, G García-Cardeña. Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circ Res 2016; 118(4): 620–636 pmid: 26892962
103 RL Engerman, TS Kern, ME Larson. Nerve conduction and aldose reductase inhibition during 5 years of diabetes or galactosaemia in dogs. Diabetologia 1994; 37(2): 141–144 pmid: 8163047
104 P Geraldes, GL King. Activation of protein kinase C isoforms and its impact on diabetic complications. Circ Res 2010; 106(8): 1319–1331 pmid: 20431074
105 N Isakov. Protein kinase C (PKC) isoforms in cancer, tumor promotion and tumor suppression. Semin Cancer Biol 2018; 48: 36–52 pmid: 28571764
106 M Land, CS Rubin. A calcium- and diacylglycerol-stimulated protein kinase C (PKC), Caenorhabditis elegans PKC-2, links thermal signals to learned behavior by acting in sensory neurons and intestinal cells. Mol Cell Biol 2017; 37(19): e00192-17 pmid: 28716951
107 M Brownlee. Biochemistry and molecular cell biology of diabetic complications. Nature 2001; 414(6865): 813–820 pmid: 11742414
108 C Brinkmann, RH Schwinger, K Brixius. Physical activity and endothelial dysfunction in type 2 diabetic patients: the role of nitric oxide and oxidative stress. Wien Med Wochenschr 2011; 161(11-12): 305–314 (in German) pmid: 21360292
109 L Kong, X Shen, L Lin, M Leitges, R Rosario, YS Zou, SF Yan. PKCβ promotes vascular inflammation and acceleration of atherosclerosis in diabetic ApoE null mice. Arterioscler Thromb Vasc Biol 2013; 33(8): 1779–1787 pmid: 23766264
110 GM Pieper, Riaz-ul-Haq. Activation of nuclear factor-κB in cultured endothelial cells by increased glucose concentration: prevention by calphostin C. J Cardiovasc Pharmacol 1997; 30(4): 528–532 pmid: 9335415
111 MB Ganz, A Seftel. Glucose-induced changes in protein kinase C and nitric oxide are prevented by vitamin E. Am J Physiol Endocrinol Metab 2000; 278(1): E146–E152 pmid: 10644549
112 K Kuboki, ZY Jiang, N Takahara, SW Ha, M Igarashi, T Yamauchi, EP Feener, TP Herbert, CJ Rhodes, GL King. Regulation of endothelial constitutive nitric oxide synthase gene expression in endothelial cells and in vivo : a specific vascular action of insulin. Circulation 2000; 101(6): 676–681 pmid: 10673261
113 M Federici, R Menghini, A Mauriello, ML Hribal, F Ferrelli, D Lauro, P Sbraccia, LG Spagnoli, G Sesti, R Lauro. Insulin-dependent activation of endothelial nitric oxide synthase is impaired by O-linked glycosylation modification of signaling proteins in human coronary endothelial cells. Circulation 2002; 106(4): 466–472 pmid: 12135947
114 A Martínez-Ruiz, S Cadenas, S Lamas. Nitric oxide signaling: classical, less classical, and nonclassical mechanisms. Free Radic Biol Med 2011; 51(1): 17–29 pmid: 21549190
115 K Wang, T Zhang, Q Dong, EC Nice, C Huang, Y Wei. Redox homeostasis: the linchpin in stem cell self-renewal and differentiation. Cell Death Dis 2013; 4(3): e537 pmid: 23492768
116 PD Ray, BW Huang, Y Tsuji. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal 2012; 24(5): 981–990 pmid: 22286106
117 M Thamsen, U Jakob. The redoxome: proteomic analysis of cellular redox networks. Curr Opin Chem Biol 2011; 15(1): 113–119 pmid: 21130023
118 KG Reddie, KS Carroll. Expanding the functional diversity of proteins through cysteine oxidation. Curr Opin Chem Biol 2008; 12(6): 746–754 pmid: 18804173
119 MJ May, S Ghosh. Signal transduction through NF-κB. Immunol Today 1998; 19(2): 80–88 pmid: 9509763
120 SH Korn, EF Wouters, N Vos, YM Janssen-Heininger. Cytokine-induced activation of nuclear factor-κB is inhibited by hydrogen peroxide through oxidative inactivation of IκB kinase. J Biol Chem 2001; 276(38): 35693–35700 pmid: 11479295
121 I Jaspers, W Zhang, A Fraser, JM Samet, W Reed. Hydrogen peroxide has opposing effects on IKK activity and IκBα breakdown in airway epithelial cells. Am J Respir Cell Mol Biol 2001; 24(6):769–777 pmid: 11415944
122 P Kapahi, T Takahashi, G Natoli, SR Adams, Y Chen, RY Tsien, M Karin. Inhibition of NF-κB activation by arsenite through reaction with a critical cysteine in the activation loop of IκB kinase. J Biol Chem 2000; 275(46): 36062–36066 pmid: 10967126
123 V Thallas-Bonke, JC Jha, SP Gray, D Barit, H Haller, HH Schmidt, MT Coughlan, ME Cooper, JM Forbes, KA Jandeleit-Dahm. Nox-4 deletion reduces oxidative stress and injury by PKC-α-associated mechanisms in diabetic nephropathy. Physiol Rep 2014; 2(11): e12192 pmid: 25367693
124 R Gopalakrishna, S Jaken. Protein kinase C signaling and oxidative stress. Free Radic Biol Med 2000; 28(9): 1349–1361 pmid: 10924854
125 B Stäuble, D Boscoboinik, A Tasinato, A Azzi. Modulation of activator protein-1 (AP-1) transcription factor and protein kinase C by hydrogen peroxide and D-α-tocopherol in vascular smooth muscle cells. Eur J Biochem 1994; 226(2): 393–402 pmid: 8001557
126 A Cuadrado, AI Rojo, G Wells, JD Hayes, SP Cousin, WL Rumsey, OC Attucks, S Franklin, AL Levonen, TW Kensler, AT Dinkova-Kostova. Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases. Nat Rev Drug Discov 2019; 18(4): 295–317 pmid: 30610225
127 M McMahon, DJ Lamont, KA Beattie, JD Hayes. Keap1 perceives stress via three sensors for the endogenous signaling molecules nitric oxide, zinc, and alkenals. Proc Natl Acad Sci USA 2010; 107(44): 18838–18843 pmid: 20956331
128 K Takaya, T Suzuki, H Motohashi, K Onodera, S Satomi, TW Kensler, M Yamamoto. Validation of the multiple sensor mechanism of the Keap1-Nrf2 system. Free Radic Biol Med 2012; 53(4): 817–827 pmid: 22732183
129 R Saito, T Suzuki, K Hiramoto, S Asami, E Naganuma, H Suda, T Iso, H Yamamoto, M Morita, L Baird, Y Furusawa, T Negishi, M Ichinose, M Yamamoto. Characterizations of three major cysteine sensors of Keap1 in stress response. Mol Cell Biol 2015; 36(2): 271–284 pmid: 26527616
130 A Uruno, Y Furusawa, Y Yagishita, T Fukutomi, H Muramatsu, T Negishi, A Sugawara, TW Kensler, M Yamamoto. The Keap1-Nrf2 system prevents onset of diabetes mellitus. Mol Cell Biol 2013; 33(15): 2996–3010 pmid: 23716596
131 H Zheng, SA Whitman, W Wu, GT Wondrak, PK Wong, D Fang, DD Zhang. Therapeutic potential of Nrf2 activators in streptozotocin-induced diabetic nephropathy. Diabetes 2011; 60(11): 3055–3066 pmid: 22025779
132 S Chuengsamarn, S Rattanamongkolgul, R Luechapudiporn, C Phisalaphong, S Jirawatnotai. Curcumin extract for prevention of type 2 diabetes. Diabetes Care 2012; 35(11): 2121–2127 pmid: 22773702
133 S Golbidi, SA Ebadi, I Laher. Antioxidants in the treatment of diabetes. Curr Diabetes Rev 2011; 7(2): 106–125 pmid: 21294707
134 J Belch, A MacCuish, I Campbell, S Cobbe, R Taylor, R Prescott, R Lee, J Bancroft, S MacEwan, J Shepherd, P Macfarlane, A Morris, R Jung, C Kelly, A Connacher, N Peden, A Jamieson, D Matthews, G Leese, J McKnight, I O’Brien, C Semple, J Petrie, D Gordon, S Pringle, R MacWalter; Prevention of Progression of Arterial Disease and Diabetes Study Group; Diabetes Registry Group; Royal College of Physicians Edinburgh. The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. BMJ 2008; 337: a1840 pmid: 18927173
135 HN Bhagavan, RK Chopra. Coenzyme Q10: absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res 2006; 40(5): 445–453 pmid: 16551570
136 JS Armstrong. Mitochondrial medicine: pharmacological targeting of mitochondria in disease. Br J Pharmacol 2007; 151(8): 1154–1165 pmid: 17519949
137 D Umpierre, PA Ribeiro, CK Kramer, CB Leitão, AT Zucatti, MJ Azevedo, JL Gross, JP Ribeiro, BD Schaan. Physical activity advice only or structured exercise training and association with HbA1c levels in type 2 diabetes: a systematic review and meta-analysis. JAMA 2011; 305(17): 1790–1799 pmid: 21540423
138 TS Church, SN Blair, S Cocreham, N Johannsen, W Johnson, K Kramer, CR Mikus, V Myers, M Nauta, RQ Rodarte, L Sparks, A Thompson, CP Earnest. Effects of aerobic and resistance training on hemoglobin A1c levels in patients with type 2 diabetes: a randomized controlled trial. JAMA 2010; 304(20): 2253–2262 pmid: 21098771
139 RJ Sigal, GP Kenny, NG Boulé, GA Wells, D Prud’homme, M Fortier, RD Reid, H Tulloch, D Coyle, P Phillips, A Jennings, J Jaffey. Effects of aerobic training, resistance training, or both on glycemic control in type 2 diabetes: a randomized trial. Ann Intern Med 2007; 147(6): 357–369 pmid: 17876019
140 B Moe, E Eilertsen, TI Nilsen. The combined effect of leisure-time physical activity and diabetes on cardiovascular mortality: the Nord-Trondelag Health (HUNT) cohort study, Norway. Diabetes Care 2013; 36(3): 690–695 pmid: 23160724
141 N Yamashita, S Hoshida, K Otsu, M Asahi, T Kuzuya, M Hori. Exercise provides direct biphasic cardioprotection via manganese superoxide dismutase activation. J Exp Med 1999; 189(11): 1699–1706 pmid: 10359573
142 SM Haffner; American Diabetes Association. Management of dyslipidemia in adults with diabetes. Diabetes Care 2003; 26(Suppl 1): S83–S86 pmid: 12502625
143 S Lee, SC Yang, MJ Heffernan, WR Taylor, N Murthy. Polyketal microparticles: a new delivery vehicle for superoxide dismutase. Bioconjug Chem 2007; 18(1): 4–7 pmid: 17226951
144 CN Grama, P Suryanarayana, MA Patil, G Raghu, N Balakrishna, MN Kumar, GB Reddy. Efficacy of biodegradable curcumin nanoparticles in delaying cataract in diabetic rat model. PLoS One 2013; 8(10): e78217 pmid: 24155984
145 M Takahashi, S Uechi, K Takara, Y Asikin, K Wada. Evaluation of an oral carrier system in rats: bioavailability and antioxidant properties of liposome-encapsulated curcumin. J Agric Food Chem 2009; 57(19): 9141–9146 pmid: 19757811
146 AE Dikalova, AT Bikineyeva, K Budzyn, RR Nazarewicz, L McCann, W Lewis, DG Harrison, SI Dikalov. Therapeutic targeting of mitochondrial superoxide in hypertension. Circ Res 2010; 107(1): 106–116 pmid: 20448215
147 D Graham, NN Huynh, CA Hamilton, E Beattie, RA Smith, HM Cochemé, MP Murphy, AF Dominiczak. Mitochondria-targeted antioxidant MitoQ10 improves endothelial function and attenuates cardiac hypertrophy. Hypertension 2009; 54(2): 322–328 pmid: 19581509
148 W Jiao, J Ji, F Li, J Guo, Y Zheng, S Li, W Xu. Activation of the NotchNox4 reactive oxygen species signaling pathway induces cell death in high glucosetreated human retinal endothelial cells. Mol Med Rep 2019; 19(1): 667–677
pmid: 30431086
149 JJ Peng, SQ Xiong, LX Ding, J Peng, XB Xia. Diabetic retinopathy: focus on NADPH oxidase and its potential as therapeutic target. Eur J Pharmacol 2019; 853: 381–387 pmid: 31009636
150 PE Pergola, P Raskin, RD Toto, CJ Meyer, JW Huff, EB Grossman, M Krauth, S Ruiz, P Audhya, H Christ-Schmidt, J Wittes, DG Warnock; BEAM Study Investigators. Bardoxolone methyl and kidney function in CKD with type 2 diabetes. N Engl J Med 2011; 365(4): 327–336 pmid: 21699484
151 Q Zhong, M Mishra, RA Kowluru. Transcription factor Nrf2-mediated antioxidant defense system in the development of diabetic retinopathy. Invest Ophthalmol Vis Sci 2013; 54(6): 3941–3948 pmid: 23633659
152 R Gopalakrishna, S Jaken. Protein kinase C signaling and oxidative stress. Free Radic Biol Med 2000; 28(9): 1349–1361 pmid: 10924854
153 R Gopalakrishna, U Gundimeda. Protein kinase C as a molecular target for cancer prevention by selenocompounds. Nutr Cancer 2001; 40(1): 55–63 pmid: 11799924
154 R Gopalakrishna, ZH Chen, U Gundimeda. Selenocompounds induce a redox modulation of protein kinase C in the cell, compartmentally independent from cytosolic glutathione: its role in inhibition of tumor promotion. Arch Biochem Biophys 1997; 348(1): 37–48 pmid: 9390172
155 F Alam, MA Islam, SH Gan, M Mohamed, TH Sasongko. DNA methylation: an epigenetic insight into type 2 diabetes mellitus. Curr Pharm Des 2016; 22(28): 4398–4419 pmid: 27229720
156 XW Lei, Q Li, JZ Zhang, YM Zhang, Y Liu, KH Yang. The protective roles of folic acid in preventing diabetic retinopathy are potentially associated with suppressions on angiogenesis, inflammation, and oxidative stress. Ophthalmic Res 2019; 62(2): 80–92 pmid: 31018207
157 KM Beard, N Shangari, B Wu, PJ O’Brien. Metabolism, not autoxidation, plays a role in α-oxoaldehyde- and reducing sugar-induced erythrocyte GSH depletion: relevance for diabetes mellitus. Mol Cell Biochem 2003; 252(1-2): 331–338 pmid: 14577607
158 S Shukla, KK Dubey. CoQ10 a super-vitamin: review on application and biosynthesis. 3 Biotech 2018; 8(5):249
159 MM Lasram, IB Dhouib, A Annabi, S El Fazaa, N Gharbi. A review on the possible molecular mechanism of action of N-acetylcysteine against insulin resistance and type-2 diabetes development. Clin Biochem 2015; 48(16-17): 1200–1208 pmid: 25920891
160 P Kamenova. Improvement of insulin sensitivity in patients with type 2 diabetes mellitus after oral administration of α-lipoic acid. Hormones (Athens) 2006; 5(4): 251–258 pmid: 17178700
161 B Kiens. Skeletal muscle lipid metabolism in exercise and insulin resistance. Physiol Rev 2006; 86(1): 205–243 pmid: 16371598
162 JS Tauskela. MitoQ—a mitochondria-targeted antioxidant. IDrugs 2007; 10(6): 399–412
pmid: 17642004
163 CS Wilcox. Effects of tempol and redox-cycling nitroxides in models of oxidative stress. Pharmacol Ther 2010; 126(2): 119–145 pmid: 20153367
Related articles from Frontiers Journals
[1] Ning Jiang, Yao Li, Ting Shu, Jing Wang. Cytokines and inflammation in adipogenesis: an updated review[J]. Front. Med., 2019, 13(3): 314-329.
[2] Xiaoqing Li, Xinxin Li, Genbei Wang, Yan Xu, Yuanyuan Wang, Ruijia Hao, Xiaohui Ma. Xiao Ke Qing improves glycometabolism and ameliorates insulin resistance by regulating the PI3K/Akt pathway in KKAy mice[J]. Front. Med., 2018, 12(6): 688-696.
[3] Liping Xuan, Zhiyun Zhao, Xu Jia, Yanan Hou, Tiange Wang, Mian Li, Jieli Lu, Yu Xu, Yuhong Chen, Lu Qi, Weiqing Wang, Yufang Bi, Min Xu. Type 2 diabetes is causally associated with depression: a Mendelian randomization analysis[J]. Front. Med., 2018, 12(6): 678-687.
[4] Jiemin Pan, Weiping Jia. Early-onset diabetes: an epidemic in China[J]. Front. Med., 2018, 12(6): 624-633.
[5] Cynthia Rajani, Wei Jia. Bile acids and their effects on diabetes[J]. Front. Med., 2018, 12(6): 608-623.
[6] Meng Dong, Jun Lin, Wonchung Lim, Wanzhu Jin, Hyuek Jong Lee. Role of brown adipose tissue in metabolic syndrome, aging, and cancer cachexia[J]. Front. Med., 2018, 12(2): 130-138.
[7] Chao Chen, Chang Wang, Chun Hu, Yachun Han, Li Zhao, Xuejing Zhu, Li Xiao, Lin Sun. Normoalbuminuric diabetic kidney disease[J]. Front. Med., 2017, 11(3): 310-318.
[8] Palka Kaur Khanuja,Satish Chander Narula,Rajesh Rajput,Rajinder Kumar Sharma,Shikha Tewari. Association of periodontal disease with glycemic control in patients with type 2 diabetes in Indian population[J]. Front. Med., 2017, 11(1): 110-119.
[9] Huiqin Zhong,Ya Shao,Ling Fan,Tangshen Zhong,Lu Ren,Yan Wang. Perceived resource support for chronic illnesses among diabetics in north-western China[J]. Front. Med., 2016, 10(2): 219-227.
[10] Juan Zheng,Shih-Lung Woo,Xiang Hu,Rachel Botchlett,Lulu Chen,Yuqing Huo,Chaodong Wu. Metformin and metabolic diseases: a focus on hepatic aspects[J]. Front. Med., 2015, 9(2): 173-186.
[11] Amma Owusu-Ansah,Sung Hee Choi,Agne Petrosiute,John J. Letterio,Alex Yee-Chen Huang. Triterpenoid inducers of Nrf2 signaling as potential therapeutic agents in sickle cell disease: a review[J]. Front. Med., 2015, 9(1): 46-56.
[12] Jie Zheng,Yuzhen Gao,Yuejuan Jing,Xiaoshuang Zhou,Yuanyuan Shi,Yanhong Li,Lihua Wang,Ruiying Wang,Maolian Li,Chuanshi Xiao,Yafeng Li,Rongshan Li. Gender differences in the relationship between plasma lipids and fasting plasma glucose in non-diabetic urban Chinese population: a cross-section study[J]. Front. Med., 2014, 8(4): 477-483.
[13] Xiaoyan Chen,Wenxia Xiao,Xinchun Li,Jianxun He,Xiaochun Huang,Yuyu Tan. In vivo evaluation of renal function using diffusion weighted imaging and diffusion tensor imaging in type 2 diabetics with normoalbuminuria versus microalbuminuria[J]. Front. Med., 2014, 8(4): 471-476.
[14] Jichun Yang, Jihong Kang, Youfei Guan. The mechanisms linking adiposopathy to type 2 diabetes[J]. Front Med, 2013, 7(4): 433-444.
[15] Tingting Wang, Shanglong Yao, Zhengyuan Xia, Michael G. Irwin. Adiponectin: mechanisms and new therapeutic approaches for restoring diabetic heart sensitivity to ischemic post-conditioning[J]. Front Med, 2013, 7(3): 301-305.
Full text