Skip Navigation
Skip to contents

Diabetes Metab J : Diabetes & Metabolism Journal

Search
OPEN ACCESS

Articles

Page Path
HOME > Diabetes Metab J > Volume 37(2); 2013 > Article
Review
Pathophysiology A Systematic Review of Oxidative Stress and Safety of Antioxidants in Diabetes: Focus on Islets and Their Defense
Udayakumar Karunakaran, Keun-Gyu Park
Diabetes & Metabolism Journal 2013;37(2):106-112.
DOI: https://doi.org/10.4093/dmj.2013.37.2.106
Published online: April 16, 2013
  • 6,038 Views
  • 92 Download
  • 136 Crossref
  • 165 Scopus

Departments of Internal Medicine, Biochemistry and Cell Biology, Research Institute of Aging and Metabolism and World Class University Program, Kyungpook National University School of Medicine, Daegu, Korea.

corresp_icon Corresponding author: Keun-Gyu Park. Division of Endocrinology and Metabolism, Department of Internal Medicine, Kyungpook National University School of Medicine, 130 Dongdeok-ro, Jung-gu, Daegu 700-721, Korea. kpark@knu.ac.kr

Copyright © 2013 Korean Diabetes Association

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

prev next
  • A growing body of evidence suggests that hyperglycemia-induced oxidative stress plays an important role in diabetic complications, especially β-cell dysfunction and failure. Under physiological conditions, reactive oxygen species serve as second messengers that facilitate signal transduction and gene expression in pancreatic β-cells. However, under pathological conditions, an imbalance in redox homeostasis leads to aberrant tissue damage and β-cell death due to a lack of antioxidant defense systems. Taking into account the vulnerability of islets to oxidative damage, induction of endogenous antioxidant enzymes or exogenous antioxidant administration has been proposed as a way to protect β-cells against diabetic insults. Here, we consider recent insights into how the redox response becomes deregulated under diabetic conditions, as well as the therapeutic benefits of antioxidants, which may provide clues for developing strategies aimed at the treatment or prevention of diabetes associated with β-cell failure.
Diabetes mellitus is a complex metabolic disorder resulting from progressive impairment of insulin secretion and insulin resistance. Normal pancreatic β-cells exhibit a dramatic response to nutrients and obesity induced insulin resistance via hyper secretion of insulin, which compensates for glucose intolerance. However, in type 2 diabetes, β-cells become unable to sustain a compensatory response, which has a deleterious effect on β-cells [1,2]. Further, there is considerable evidence suggesting that chronic elevation of glucose leads to the generation of reactive oxygen species (ROS), resulting in increased oxidative stress in β-cells [3-5]. As a result, β-cells become worsened with respect to both insulin secretion and action due to their ability to directly damage and oxidize DNA, protein, and lipids. In addition to macromolecular damage, ROS can activate a number of cellular stress-sensitive pathways that have been linked to insulin resistance and decreased insulin secretion [6]. In order to neutralize ROS, cells are equipped with antioxidant defense mechanisms capable of combating oxidative stress. Intriguingly, compared to other tissues, β-cells have a lower abundance of antioxidant defense enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) [7,8]. Thus, due to the low antioxidant defense status of islets, excessive ROS lead to oxidative stress during β-cell dysfunction. As such, administration of antioxidant supplements can increase the defense capacity of islet cells to cope with oxidative stress [9-11]. On the other hand, increasing evidence suggests that H2O2 molecules play a role in glucose stimulated insulin secretion (GSIS) [12,13]. Consistent with these reports, induction of endogenous antioxidant capacity in β-cells abrogates ROS signaling and reduces GSIS. Based on these studies, the imbalance between ROS signaling and antioxidant defense can be implicated in diabetes-associated β-cell dysfunction.
Effect of oxidative stress on hyperglycemia
An overwhelming body of evidence indicates that oxidative stress can lead to both cell and tissue injury. Indeed, excess production of such reactive species can be toxic and exert cytostatic effects that cause membrane damage and activate cell death pathways. Healthy pancreatic β-cells exhibit a dramatic response to nutrients and obesity-associated insulin resistance through hypersecretion of insulin in order to maintain energy homeostasis; however, through a complex process that occurs over an extended period of time, β-cells can become unable to sustain a compensatory response, leading to β-cell dysfunction and death [2]. Many studies have suggested that chronic exposure of β-cells to high levels of glucose may contribute to impaired β-cell function [14], resulting in increased glycolytic flux and subsequent production of reducing equivalents leading to production of ROS, including superoxide, hydrogen peroxide, and hydroxyl radicals. Superoxide can subsequently be converted to H2O2 by mitochondrial SOD followed by H2O and oxygen by GPx and catalase. Indeed, several in vitro and in vivo studies have demonstrated that superoxide generation is increased in diabetes. For example, Ihara et al. [15] reported increased oxidative stress markers in Goto-Kakizaki rat β-cells compared with Wistar rat islets [15-17]. In addition, there are several key metabolic pathways activated during hyperglycemia-induced superoxide production, namely, increased polyol pathway activity, increased advanced glycation end products (AGEs) pathway activity, activation of the protein kinase C (PKC) isoform, and increased hexosamine pathway flux. As such, hyperglycemia induced conversion of glucose to sorbitol leads to a concomitant decrease of nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione, which in turn is responsible for the loss of antioxidant equivalents that are more susceptible to elevated intracellular oxidative stress [18]. Under diabetic conditions, an increased flux of glucose through hexosamine biosynthesis pathway (HBP) leads to the formation of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), an end-product of HBP. Using UDP-GlcNAc as a substrate, O-linked N-acetylglucosamine transferase (OGT) catalyzes the transfer of GlcNAc via O-linkages to specific serine or threonine residues of various target proteins. Indeed, D'Alessandris et al. [19] demonstrated that the increased flux of glucose via HBP impairs insulin-signaling pathways, while other studies have shown that hyperglycemia mediated increases in both UDP-GlcNAc and O-GlcNAcylation leads to both oxidative and endoplasmic reticulum stress, which have been shown to cause chronic inflammation and insulin resistance in other cell types [20]. Furthermore, Kaneto et al. [21] demonstrated increased hydrogen peroxide formation by glucosamine in isolated rat islet cells. In the case of AGEs, glucose reacts with a free amino group to produce adduct formation, which in turn has been shown to interfere with target cell integrity or induce ROS production [22]. Likewise, Jiang et al. [23] demonstrated increased production of hydrogen peroxide with AGEs. Under hyperglycemic conditions, elevated levels of diacylglycerol (DAG) activate PKC, which subsequently increase oxidants such as H2O2 via PKC dependent activation of NADPH oxidase [24]. The above-mentioned pathways clearly show that hyperglycemia-induced overproduction of superoxide by mitochondria is capable of driving multiple pathways [25].
Effect of oxidative stress on lipotoxicity
Recent studies have suggested that elevated glucose along with circulating free fatty acid (FFA) originating from intra-abdominal fat stores is the major culprits of β-cell dysfunction. Indeed, although the exact cause of the metabolic deterioration of β-cells is unknown, several hypotheses have been proposed including mitochondrial dysfunction, oxidative stress, endoplasmic stress, and ceramide formation [26,27]. Several lines of in vitro evidence have indicated that elevated FFA has an adverse effect on mitochondrial function, leading to uncoupling of oxidative phosphorylation and ROS generation [28,29]. Thus, oxidative stress and mitochondrial dysfunction contribute to impaired endogenous antioxidant defenses. In addition, FFA induced formation of ceramide induces generation of ROS and DNA fragmentation [30]. Recent experimental evidence suggests that H2O2 formation in peroxisomes mediates lipotoxicity induced β-cell apoptosis [31]. Specifically, Bindokas et al. [32] quantified superoxide production in islets isolated from Zucker lean fatty (ZLF) and Zucker diabetic fatty (ZDF) rats, and showed that increased superoxide production in ZLF islets was comparable to that of islets of ZDF rats in the presence of glucose. In addition, the resting superoxide content of ZDF rat islets was higher than Zucker lean control islets with perturbed mitochondrial morphology [32].
FFA mediated activation of nuclear factor kappa B contributes to cytokine production and leads to the generation of nitric oxide (NO) through inducible NO synthase (iNOS) expression [33]. In this way, iNOS can result in the overproduction of NO, which in turn can react with superoxide to produce the even more toxic product peroxynitrite. Shimabukuro et al. [34] showed that exposure of prediabetic ZDF rats to FFA upregulates iNOS expression, resulting in a fourfold rise in NO formation and reduced insulin output. As discussed above, generation of ROS and reactive nitrogen species (RNS), as well as the subsequent increase in oxidative stress, may play a central role in the development of diabetes (Fig. 1).
Antioxidant response of islets against oxidative stress
As discussed above, oxidative stress has been associated with β-cell dysfunction in diabetic condition due to their poor antioxidant defense mechanisms. Indeed, there is a delicate balance between oxidants and antioxidants in health and disease, the proper balance of which is essential for cell survival. Thus, redox status is dependent on the degree to which a cell's components exist in an oxidative state, whereby a reducing environment within cells can help to prevent oxidative stress. Such a reducing environment can be maintained by the action of antioxidant enzymes and substances such as glutathione and enzymes such as SOD and catalase, both of which serve to remove ROS. Therefore, induction of endogenous antioxidant enzymes may strengthen islets against detrimental effect of ROS. The main players of intrinsic antioxidant enzymes of islets are SOD, catalase, and GPx, which, compared to liver contents, are 30% and 15% less for SOD and glutathione and catalase, respectively [8,35]. Lortz and Tiedge [36] revealed overexpression of SOD and catalase protects islets against ROS induced impairment of insulin synthesis. In addition, adenoviral mediated over expression GPx has been shown to protect insulin producing INS-1 cells against ROS and RNS insult [37]. Moreover, overexpression of catalase reduces the susceptibility of human and rat pancreatic islets to oxidative stress and preserves insulin secretory capacity [38]. Artificial overexpression of mitochondrial catalase also preferentially protects against oxidative injury and expression of proinflammatory cytokines [39]. In contrast, the ability to overexpress catalase in FVB mice can protect islets against H2O2 and streptozotocin (STZ) toxicity, as well as cytokine toxicity [40] and β-cell specific overexpression of cytoplasmic catalase and methallothionein, which can augment diabetes after cyclophosphamide treatment [41]. In addition, it should be noted that changing the balance of mitochondrial enzymes and increasing production of β-cells can alter susceptibility to dysfunction and development of diabetes.
Many studies have shown that overexpression of UCP2 downregulates levels of ROS [11,12]. Likewise, a study by Kaneto et al. [9] showed that N-acetyl cysteine, along with vitamins C and E, protects metabolically deregulated islets of C57BL/KSJ-db/db mice. Further, alpha-lipoic acid, a dithiol compound and cofactor in mitochondrial energy metabolism, can directly scavenge ROS and RNS in pancreatic islet cells [42]. Administration of alpha-lipoic acid provides a remarkable range of positive therapeutic benefits in nonobese diabetic mice treated with cyclophosphamide [43]. Furthermore, alpha-lipoic acid reduces oxidizing forms of antioxidants including vitamin C and E, as well as elevates GSH levels via its ability to increase cysteine uptake [44]. In addition, a number of reports have shown that alpha lipoic acid improves glucose disposal and reduces body weight in diabetic obese patients [45-47]. Furthermore, Bast and Haenen [48] showed that lipoic acid is capable of reducing an essential component of the mitochondrial respiratory complex cofactor ubiquinone. In support of this observation, exogenous administration of CQ10 blocks cytokine mediated inhibition of GSIS [49].
In the present study, a search of novel therapeutic agents identified a set of plant derived flavanoids that exhibited a broad bioactivity spectrum. The identified agents displayed a remarkable array of biochemical and pharmacological characteristics similar to their proposed antioxidant properties, namely, quercetin [50], curcumin [51], ginseng [52], genistein [53], and Epigallocatechin gallate [54] (Fig. 2). The biological properties of the above mentioned flavanoids were identified by limited production of ROS or a scavenging approach based on alternative nonoxidants, including the regulation of cell signaling and gene expression, which comprised vital cellular functions.
Experimental evidence shows that oxidative stress contributes to β-cell dysfunction and failure in diabetic conditions. Likewise, changes in redox status and depletion of antioxidants occur during oxidative stress induced dysfunction, which suggest the importance of ROS as a signaling molecule in GSIS. Meanwhile, numerous studies have demonstrated that antioxidant therapy potently inhibits ROS generation and eliminates oxidative stress. However, use of these compounds may have limited therapeutic relevance due to their interference with the physiological redox balance. Thus, understanding this complex scenario and determining the proper administration of antioxidants may have a considerable impact on the treatment of β-cell failure during diabetes.

No potential conflict of interest relevant to this article was reported.

  • 1. Porte D Jr. Clinical importance of insulin secretion and its interaction with insulin resistance in the treatment of type 2 diabetes mellitus and its complications. Diabetes Metab Res Rev 2001;17:181-188. ArticlePubMed
  • 2. Kahn SE. The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia 2003;46:3-19. ArticlePubMedPDF
  • 3. Rehman A, Nourooz-Zadeh J, Moller W, Tritschler H, Pereira P, Halliwell B. Increased oxidative damage to all DNA bases in patients with type II diabetes mellitus. FEBS Lett 1999;448:120-122. ArticlePubMedPDF
  • 4. Sakuraba H, Mizukami H, Yagihashi N, Wada R, Hanyu C, Yagihashi S. Reduced beta-cell mass and expression of oxidative stress-related DNA damage in the islet of Japanese type II diabetic patients. Diabetologia 2002;45:85-96. ArticlePubMedPDF
  • 5. Mohamed AK, Bierhaus A, Schiekofer S, Tritschler H, Ziegler R, Nawroth PP. The role of oxidative stress and NF-kappaB activation in late diabetic complications. Biofactors 1999;10:157-167. ArticlePubMed
  • 6. Evans JL, Goldfine ID, Maddux BA, Grodsky GM. Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr Rev 2002;23:599-622. ArticlePubMedPDF
  • 7. Grankvist K, Marklund SL, Taljedal IB. CuZn-superoxide dismutase, Mn-superoxide dismutase, catalase and glutathione peroxidase in pancreatic islets and other tissues in the mouse. Biochem J 1981;199:393-398. ArticlePubMedPMCPDF
  • 8. Lenzen S, Drinkgern J, Tiedge M. Low antioxidant enzyme gene expression in pancreatic islets compared with various other mouse tissues. Free Radic Biol Med 1996;20:463-466. ArticlePubMed
  • 9. Kaneto H, Kajimoto Y, Miyagawa J, Matsuoka T, Fujitani Y, Umayahara Y, Hanafusa T, Matsuzawa Y, Yamasaki Y, Hori M. Beneficial effects of antioxidants in diabetes: possible protection of pancreatic beta-cells against glucose toxicity. Diabetes 1999;48:2398-2406. ArticlePubMedPDF
  • 10. Kubisch HM, Wang J, Bray TM, Phillips JP. Targeted overexpression of Cu/Zn superoxide dismutase protects pancreatic beta-cells against oxidative stress. Diabetes 1997;46:1563-1566. ArticlePubMed
  • 11. Pi J, Bai Y, Zhang Q, Wong V, Floering LM, Daniel K, Reece JM, Deeney JT, Andersen ME, Corkey BE, Collins S. Reactive oxygen species as a signal in glucose-stimulated insulin secretion. Diabetes 2007;56:1783-1791. ArticlePubMedPDF
  • 12. Affourtit C, Jastroch M, Brand MD. Uncoupling protein-2 attenuates glucose-stimulated insulin secretion in INS-1E insulinoma cells by lowering mitochondrial reactive oxygen species. Free Radic Biol Med 2011;50:609-616. ArticlePubMedPMC
  • 13. Saadeh M, Ferrante TC, Kane A, Shirihai O, Corkey BE, Deeney JT. Reactive oxygen species stimulate insulin secretion in rat pancreatic islets: studies using mono-oleoyl-glycerol. PLoS One 2012;7:e30200ArticlePubMedPMC
  • 14. LeRoith D, Taylor SI, Olefsky JM. Chapter 11. Glucose toxicity of the β-cell: cellular and molecular mechanisms. Diabetes mellitus: a fundamental and clinical text. 2000. 2nd ed. Philadelphia: Lippincott Williams & Wilkins; p. 125-132.
  • 15. Ihara Y, Toyokuni S, Uchida K, Odaka H, Tanaka T, Ikeda H, Hiai H, Seino Y, Yamada Y. Hyperglycemia causes oxidative stress in pancreatic beta-cells of GK rats, a model of type 2 diabetes. Diabetes 1999;48:927-932. ArticlePubMedPDF
  • 16. Maritim AC, Sanders RA, Watkins JB 3rd. Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol 2003;17:24-38. ArticlePubMed
  • 17. Tang C, Han P, Oprescu AI, Lee SC, Gyulkhandanyan AV, Chan GN, Wheeler MB, Giacca A. Evidence for a role of superoxide generation in glucose-induced beta-cell dysfunction in vivo. Diabetes 2007;56:2722-2731. PubMed
  • 18. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001;414:813-820. ArticlePubMedPDF
  • 19. D'Alessandris C, Andreozzi F, Federici M, Cardellini M, Brunetti A, Ranalli M, Del Guerra S, Lauro D, Del Prato S, Marchetti P, Lauro R, Sesti G. Increased O-glycosylation of insulin signaling proteins results in their impaired activation and enhanced susceptibility to apoptosis in pancreatic beta-cells. FASEB J 2004;18:959-961. ArticlePubMedPDF
  • 20. Werstuck GH, Khan MI, Femia G, Kim AJ, Tedesco V, Trigatti B, Shi Y. Glucosamine-induced endoplasmic reticulum dysfunction is associated with accelerated atherosclerosis in a hyperglycemic mouse model. Diabetes 2006;55:93-101. ArticlePubMedPDF
  • 21. Kaneto H, Xu G, Song KH, Suzuma K, Bonner-Weir S, Sharma A, Weir GC. Activation of the hexosamine pathway leads to deterioration of pancreatic beta-cell function through the induction of oxidative stress. J Biol Chem 2001;276:31099-31104. PubMed
  • 22. Yan SD, Schmidt AM, Anderson GM, Zhang J, Brett J, Zou YS, Pinsky D, Stern D. Enhanced cellular oxidant stress by the interaction of advanced glycation end products with their receptors/binding proteins. J Biol Chem 1994;269:9889-9897. ArticlePubMed
  • 23. Jiang ZY, Woollard AC, Wolff SP. Hydrogen peroxide production during experimental protein glycation. FEBS Lett 1990;268:69-71. ArticlePubMedPDF
  • 24. Inoguchi T, Li P, Umeda F, Yu HY, Kakimoto M, Imamura M, Aoki T, Etoh T, Hashimoto T, Naruse M, Sano H, Utsumi H, Nawata H. High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C: dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes 2000;49:1939-1945. ArticlePubMedPDF
  • 25. Nishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T, Kaneda Y, Yorek MA, Beebe D, Oates PJ, Hammes HP, Giardino I, Brownlee M. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 2000;404:787-790. ArticlePubMedPDF
  • 26. Robertson RP, Harmon J, Tran PO, Poitout V. Beta-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes. Diabetes 2004;53(Suppl 1):S119-S124. PubMed
  • 27. Cnop M, Welsh N, Jonas JC, Jorns A, Lenzen S, Eizirik DL. Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: many differences, few similarities. Diabetes 2005;54(Suppl 2):S97-S107. PubMed
  • 28. Bakker SJ, RG IJ, Teerlink T, Westerhoff HV, Gans RO, Heine RJ. Cytosolic triglycerides and oxidative stress in central obesity: the missing link between excessive atherosclerosis, endothelial dysfunction, and beta-cell failure. Atherosclerosis 2000;148:17-21. ArticlePubMed
  • 29. El-Assaad W, Joly E, Barbeau A, Sladek R, Buteau J, Maestre I, Pepin E, Zhao S, Iglesias J, Roche E, Prentki M. Glucolipotoxicity alters lipid partitioning and causes mitochondrial dysfunction, cholesterol, and ceramide deposition and reactive oxygen species production in INS832/13 ss-cells. Endocrinology 2010;151:3061-3073. PubMed
  • 30. Lupi R, Dotta F, Marselli L, Del Guerra S, Masini M, Santangelo C, Patane G, Boggi U, Piro S, Anello M, Bergamini E, Mosca F, Di Mario U, Del Prato S, Marchetti P. Prolonged exposure to free fatty acids has cytostatic and pro-apoptotic effects on human pancreatic islets: evidence that beta-cell death is caspase mediated, partially dependent on ceramide pathway, and Bcl-2 regulated. Diabetes 2002;51:1437-1442. PubMed
  • 31. Elsner M, Gehrmann W, Lenzen S. Peroxisome-generated hydrogen peroxide as important mediator of lipotoxicity in insulin-producing cells. Diabetes 2011;60:200-208. ArticlePubMedPDF
  • 32. Bindokas VP, Kuznetsov A, Sreenan S, Polonsky KS, Roe MW, Philipson LH. Visualizing superoxide production in normal and diabetic rat islets of Langerhans. J Biol Chem 2003;278:9796-9801. ArticlePubMed
  • 33. Igoillo-Esteve M, Marselli L, Cunha DA, Ladriere L, Ortis F, Grieco FA, Dotta F, Weir GC, Marchetti P, Eizirik DL, Cnop M. Palmitate induces a pro-inflammatory response in human pancreatic islets that mimics CCL2 expression by beta cells in type 2 diabetes. Diabetologia 2010;53:1395-1405. ArticlePubMedPDF
  • 34. Shimabukuro M, Ohneda M, Lee Y, Unger RH. Role of nitric oxide in obesity-induced beta cell disease. J Clin Invest 1997;100:290-295. ArticlePubMedPMC
  • 35. Tiedge M, Lortz S, Drinkgern J, Lenzen S. Relation between antioxidant enzyme gene expression and antioxidative defense status of insulin-producing cells. Diabetes 1997;46:1733-1742. ArticlePubMed
  • 36. Lortz S, Tiedge M. Sequential inactivation of reactive oxygen species by combined overexpression of SOD isoforms and catalase in insulin-producing cells. Free Radic Biol Med 2003;34:683-688. ArticlePubMed
  • 37. Moriscot C, Richard MJ, Favrot MC, Benhamou PY. Protection of insulin-secreting INS-1 cells against oxidative stress through adenoviral-mediated glutathione peroxidase overexpression. Diabetes Metab 2003;29(2 Pt 1):145-151. ArticlePubMed
  • 38. Benhamou PY, Moriscot C, Richard MJ, Beatrix O, Badet L, Pattou F, Kerr-Conte J, Chroboczek J, Lemarchand P, Halimi S. Adenovirus-mediated catalase gene transfer reduces oxidant stress in human, porcine and rat pancreatic islets. Diabetologia 1998;41:1093-1100. ArticlePubMedPDF
  • 39. Gurgul E, Lortz S, Tiedge M, Jorns A, Lenzen S. Mitochondrial catalase overexpression protects insulin-producing cells against toxicity of reactive oxygen species and proinflammatory cytokines. Diabetes 2004;53:2271-2280. ArticlePubMedPDF
  • 40. Xu B, Moritz JT, Epstein PN. Overexpression of catalase provides partial protection to transgenic mouse beta cells. Free Radic Biol Med 1999;27:830-837. ArticlePubMed
  • 41. Li X, Chen H, Epstein PN. Metallothionein and catalase sensitize to diabetes in nonobese diabetic mice: reactive oxygen species may have a protective role in pancreatic beta-cells. Diabetes 2006;55:1592-1604. PubMed
  • 42. Lee BW, Kwon SJ, Chae HY, Kang JG, Kim CS, Lee SJ, Yoo HJ, Kim JH, Park KS, Ihm SH. Dose-related cytoprotective effect of alpha-lipoic acid on hydrogen peroxide-induced oxidative stress to pancreatic beta cells. Free Radic Res 2009;43:68-77. PubMed
  • 43. Faust A, Burkart V, Ulrich H, Weischer CH, Kolb H. Effect of lipoic acid on cyclophosphamide-induced diabetes and insulitis in non-obese diabetic mice. Int J Immunopharmacol 1994;16:61-66. ArticlePubMed
  • 44. Busse E, Zimmer G, Schopohl B, Kornhuber B. Influence of alpha-lipoic acid on intracellular glutathione in vitro and in vivo. Arzneimittelforschung 1992;42:829-831. PubMed
  • 45. Koh EH, Lee WJ, Lee SA, Kim EH, Cho EH, Jeong E, Kim DW, Kim MS, Park JY, Park KG, Lee HJ, Lee IK, Lim S, Jang HC, Lee KH, Lee KU. Effects of alpha-lipoic acid on body weight in obese subjects. Am J Med 2011;124:85Article
  • 46. Jacob S, Henriksen EJ, Tritschler HJ, Augustin HJ, Dietze GJ. Improvement of insulin-stimulated glucose-disposal in type 2 diabetes after repeated parenteral administration of thioctic acid. Exp Clin Endocrinol Diabetes 1996;104:284-288. ArticlePubMed
  • 47. Estrada DE, Ewart HS, Tsakiridis T, Volchuk A, Ramlal T, Tritschler H, Klip A. Stimulation of glucose uptake by the natural coenzyme alpha-lipoic acid/thioctic acid: participation of elements of the insulin signaling pathway. Diabetes 1996;45:1798-1804. ArticlePubMed
  • 48. Bast A, Haenen GR. Lipoic acid: a multifunctional antioxidant. Biofactors 2003;17:207-213. ArticlePubMed
  • 49. Schroeder MM, Belloto RJ Jr, Hudson RA, McInerney MF. Effects of antioxidants coenzyme Q10 and lipoic acid on interleukin-1 beta-mediated inhibition of glucose-stimulated insulin release from cultured mouse pancreatic islets. Immunopharmacol Immunotoxicol 2005;27:109-122. PubMed
  • 50. Coskun O, Kanter M, Korkmaz A, Oter S. Quercetin, a flavonoid antioxidant, prevents and protects streptozotocin-induced oxidative stress and beta-cell damage in rat pancreas. Pharmacol Res 2005;51:117-123. PubMed
  • 51. Meghana K, Sanjeev G, Ramesh B. Curcumin prevents streptozotocin-induced islet damage by scavenging free radicals: a prophylactic and protective role. Eur J Pharmacol 2007;577:183-191. ArticlePubMed
  • 52. Kim HY, Kim K. Protective effect of ginseng on cytokine-induced apoptosis in pancreatic beta-cells. J Agric Food Chem 2007;55:2816-2823. ArticlePubMed
  • 53. Kim EK, Kwon KB, Song MY, Seo SW, Park SJ, Ka SO, Na L, Kim KA, Ryu DG, So HS, Park R, Park JW, Park BH. Genistein protects pancreatic beta cells against cytokine-mediated toxicity. Mol Cell Endocrinol 2007;278:18-28. PubMed
  • 54. Cai EP, Lin JK. Epigallocatechin gallate (EGCG) and rutin suppress the glucotoxicity through activating IRS2 and AMPK signaling in rat pancreatic beta cells. J Agric Food Chem 2009;57:9817-9827. ArticlePubMed
Fig. 1
Current working model of reactive oxygen species (ROS) generation via hyperglycemia, free fatty acids, and cytokines. Excess generation of mitochondrial ROS activates stress sensitive pathways including polyol, advanced glycation end products (AGEs), protein kinase C (PKC), and hexosamine flux. Detailed mechanisms are discussed in the text of the present study. NF-κB, nuclear factor kappa B; JNK, c-Jun N-terminal kinases; JAK, Janus kinase; STAT, signal transducer and activator of transcription.
dmj-37-106-g001.jpg
Fig. 2
Proposed causative link of β-cell dysfunction between reactive oxygen species (ROS) and antioxidants. In the proposed mechanism, glucose stimulates intracellular ROS generation, which leads to glucose stimulated insulin secretion (GSIS). Likewise, chronic exposure to free radicals leads to β-cell dysfunction and death. Administration of dietary antioxidants may inhibit free radical induced cell dysfunction; however, they may also interfere with glucose induced ROS signaling in GSIS. SOD, superoxide dismutase; GPx, glutathione peroxidase; Nrf2, nuclear factor erythroid 2-related factor 2.
dmj-37-106-g002.jpg

Figure & Data

References

    Citations

    Citations to this article as recorded by  
    • Association Between Serum Ferritin and the Duration of Type 2 Diabetes Mellitus in a Tertiary Care Hospital in Chennai
      Sankar Arumugam, Anbalagan Suyambulingam
      Cureus.2024;[Epub]     CrossRef
    • Pancreatic Parenchymal Atrophy and Pancreatic Fat Accumulation Measured by Multidetector Computed Tomography as a Stable Marker of Chronic Progressive Type 2 Diabetes Mellitus—A Cross Sectional Observational Study
      Kshipra Devadiga, Khanak K Nandolia, Mahendra Singh, Pankaj Sharma, Udit Chauhan, Ravi Kant
      Avicenna Journal of Medicine.2024; 14(01): 060.     CrossRef
    • Toward Ultrasound Molecular Imaging of Endothelial Dysfunction in Diabetes: Targets, Strategies, and Challenges
      Jiahan Liu, Chen Wang, Shuo Qiu, Wenqi Sun, Guodong Yang, Lijun Yuan
      ACS Applied Bio Materials.2024; 7(3): 1416.     CrossRef
    • Bisphenol a accelerates the glucolipotoxicity-induced dysfunction of rat insulinoma cell lines: An implication for a potential risk of environmental bisphenol a exposure for individuals susceptible to type 2 diabetes
      Chengmeng Huang, Xiaolin Chen, Zedong Ouyang, Lingxue Meng, Jian Liu, Qihua Pang, Ruifang Fan
      Toxicology in Vitro.2024; 99: 105866.     CrossRef
    • Benefits of Quercetin on Glycated Hemoglobin, Blood Pressure, PiKo-6 Readings, Night-Time Sleep, Anxiety, and Quality of Life in Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Trial
      Aikaterini E. Mantadaki, Manolis Linardakis, Maria Tsakiri, Stella Baliou, Persefoni Fragkiadaki, Elena Vakonaki, Manolis N. Tzatzarakis, Aristidis Tsatsakis, Emmanouil K. Symvoulakis
      Journal of Clinical Medicine.2024; 13(12): 3504.     CrossRef
    • Effect of Vitamin C on Blood Glucose Levels, Glycosylated Hemoglobin, and Serum Lipid Profile in Patients with Type 2 Diabetes Mellitus: A Prospective Study
      Fehmi M. Mukadam, Ujwala P. Gawali, Shraddha M. Pore
      Journal of Diabetology.2024; 15(3): 273.     CrossRef
    • A Comprehensive Review on the Significance of Cysteine in Various Metabolic Disorders; Particularly CVD, Diabetes, Renal Dysfunction, and Ischemic Stroke
      Namra Aziz, Pranay Wal, Rishika Sinha, Prashant Ramesh Shirode, GunoSindhu Chakraborthy, Mukesh Chandra Sharma, Pankaj Kumar
      Current Protein & Peptide Science.2024; 25(9): 682.     CrossRef
    • Interference of altered plasma trace elements profile with hyperhomocysteinemia and oxidative stress damage to insulin secretion dysfunction in Psammomys obesus: focus on the selenium
      Asma Bouazza, Eric Fontaine, Xavier Leverve, Elhadj-Ahmed Koceir
      Archives of Physiology and Biochemistry.2023; 129(2): 505.     CrossRef
    • Vanillic acid potentiates insulin secretion and prevents pancreatic β-cells cytotoxicity under H2O2-induced oxidative stress
      Chandan Muddahally Naganna, K. Yogendra Prasad, V. P. Mahendra, P. Ganesan, Ravi Kumar
      Molecular Biology Reports.2023; 50(2): 1311.     CrossRef
    • Pancreatic β-cell dysfunction in type 2 diabetes: Implications of inflammation and oxidative stress
      Phiwayinkosi V Dludla, Sihle E Mabhida, Khanyisani Ziqubu, Bongani B Nkambule, Sithandiwe E Mazibuko-Mbeje, Sidney Hanser, Albert Kotze Basson, Carmen Pheiffer, Andre Pascal Kengne
      World Journal of Diabetes.2023; 14(3): 130.     CrossRef
    • Redox Balance in Type 2 Diabetes: Therapeutic Potential and the Challenge of Antioxidant-Based Therapy
      Lital Argaev-Frenkel, Tovit Rosenzweig
      Antioxidants.2023; 12(5): 994.     CrossRef
    • Polygenic Variants Linked to Oxidative Stress and the Antioxidant System Are Associated with Type 2 Diabetes Risk and Interact with Lifestyle Factors
      Youngjin Choi, Hyuk-Ku Kwon, Sunmin Park
      Antioxidants.2023; 12(6): 1280.     CrossRef
    • Food Anthocyanins: Malvidin and Its Glycosides as Promising Antioxidant and Anti-Inflammatory Agents with Potential Health Benefits
      Anna Merecz-Sadowska, Przemysław Sitarek, Tomasz Kowalczyk, Karolina Zajdel, Mariusz Jęcek, Paweł Nowak, Radosław Zajdel
      Nutrients.2023; 15(13): 3016.     CrossRef
    • Selenium—More than Just a Fortuitous Sulfur Substitute in Redox Biology
      Luisa B. Maia, Biplab K. Maiti, Isabel Moura, José J. G. Moura
      Molecules.2023; 29(1): 120.     CrossRef
    • Nitroxyl Radical as a Theranostic Contrast Agent in Magnetic Resonance Redox Imaging
      Ken-ichiro Matsumoto, Ikuo Nakanishi, Zhivko Zhelev, Rumiana Bakalova, Ichio Aoki
      Antioxidants & Redox Signaling.2022; 36(1-3): 95.     CrossRef
    • Speciation study and biological activity of copper (II) complexes with picolinic and 6-methylpicolinic acid with different components of blood serum of low molecular mass in KNO3 1.0 mol·L−1 at 25 °C
      Edgar Del Carpio, María L. Serrano, Lino Hernández, Waleska Madden, Vito Lubes, Vanessa R. Landaeta, Rafael E. Rodríguez-Lugo, Giuseppe Lubes, Anita Stern, Carlos Ciangherotti, Lissette Jiménez
      Polyhedron.2022; 211: 115562.     CrossRef
    • Pharmaceutical Formulation and Polymer Chemistry for Cell Encapsulation Applied to the Creation of a lab-on-a-chip bio-microsystem
      Armin Mooranian, Melissa Jones, Corina Mihaela Ionescu, Daniel Walker, Susbin Raj Wagle, Bozica Kovacevic, Jacqueline Chester, Thomas Foster, Edan Johnston, Momir Mikov, Hani Al-Salami
      Therapeutic Delivery.2022; 13(1): 51.     CrossRef
    • Racial Differences in Pain, Nutrition, and Oxidative Stress
      Larissa J. Strath, Robert E. Sorge
      Pain and Therapy.2022; 11(1): 37.     CrossRef
    • Aerobic training reduces pancreatic fat content and improves β‐cell function: A randomized controlled trial using IDEAL‐IQ magnetic resonance imaging
      Min Li, Qidong Zheng, Joshua D. Miller, Panpan Zuo, Xiaodan Yuan, Jitao Feng, Chao Liu, Shan Bao, Qingqing Lou
      Diabetes/Metabolism Research and Reviews.2022;[Epub]     CrossRef
    • Synthesis, Antioxidant, and Antidiabetic Activities of Ketone Derivatives of Succinimide
      Bushra Waheed, Syed Muhammad Mukarram Shah, Fida Hussain, Mohammad Ijaz Khan, Anwar Zeb, Muhammad Saeed Jan, Arpita Roy
      Evidence-Based Complementary and Alternative Medicine.2022; 2022: 1.     CrossRef
    • Recent Advances and Mechanistic Insights into Antibacterial Activity, Antibiofilm Activity, and Cytotoxicity of Silver Nanoparticles
      Neetu Tripathi, Manoj Kumar Goshisht
      ACS Applied Bio Materials.2022; 5(4): 1391.     CrossRef
    • Chemical speciation, antioxidant activity and molecular docking of copper(II) complexes with pyridinedicarboxylic acids and different ligands of low molecular mass
      Edgar Del Carpio, María L. Serrano, Lino Hernández, Waleska Madden, Vito Lubes, Vanessa R. Landaeta, Rafael E. Rodríguez-Lugo, Giuseppe Lubes, Anita Stern, Carlos Ciangherotti, Lissette Jiménez
      Physics and Chemistry of Liquids.2022; 60(6): 943.     CrossRef
    • Inflammaging and Osteoarthritis
      Francesca Motta, Elisa Barone, Antonio Sica, Carlo Selmi
      Clinical Reviews in Allergy & Immunology.2022; 64(2): 222.     CrossRef
    • Oxidative Stress in Ageing and Chronic Degenerative Pathologies: Molecular Mechanisms Involved in Counteracting Oxidative Stress and Chronic Inflammation
      Thobekile S. Leyane, Sandy W. Jere, Nicolette N. Houreld
      International Journal of Molecular Sciences.2022; 23(13): 7273.     CrossRef
    • Validation of the traditional medicinal use of a Mexican endemic orchid (Prosthechea karwinskii) through UPLC-ESI-qTOF-MS/MS characterization of its bioactive compounds
      Gabriela Soledad Barragán-Zarate, Luicita Lagunez-Rivera, Rodolfo Solano, Candy Carranza-Álvarez, Diego Manuel Hernández-Benavides, Gerard Vilarem
      Heliyon.2022; 8(7): e09867.     CrossRef
    • N-acetyl-L-cysteine ameliorates hepatocyte pyroptosis of dog type 1 diabetes mellitus via suppression of NLRP3/NF-κB pathway
      Haihua Huo, Haitong Wu, Feiyang Ma, Xinrun Li, Jianzhao Liao, Lianmei Hu, Qingyue Han, Ying Li, Jiaqiang Pan, Hui Zhang, Zhaoxin Tang, Jianying Guo
      Life Sciences.2022; 306: 120802.     CrossRef
    • Vitamin D regulates insulin and ameliorates apoptosis and oxidative stress in pancreatic tissues of rats with streptozotocin-induced diabetes
      Fatima El Zahra M. Fathi, Kadry M. Sadek, Asmaa F. Khafaga, Abdel Wahab Al senosy, Hanan A. Ghoniem, Sahar Fayez, Mohamed F. Zeweil
      Environmental Science and Pollution Research.2022; 29(60): 90219.     CrossRef
    • Hypoglycemic, Hypolipidemic and Antioxidant Potentials of Ethanolic Stem Bark Extract of Anacardium occidentale in Streptozotocin-Induced Diabetic Rats
      F. A Bamisaye, R. A Ibrahim, A.O. Sulyman, A.O. Jubril, Olawale Ajuwon
      Nigerian Journal of Physiological Sciences.2022; 37(1): 137.     CrossRef
    • Protective Effects of the Bilobalide on Retinal Oxidative Stress and Inflammation in Streptozotocin-Induced Diabetic Rats
      Qiang Su, Jing Dong, Donglei Zhang, Lu Yang, Rupak Roy
      Applied Biochemistry and Biotechnology.2022; 194(12): 6407.     CrossRef
    • Effects of Psychotropic Medication on Somatic Sterol Biosynthesis of Adult Mice
      Marta Balog, Allison C Anderson, Marija Heffer, Zeljka Korade, Karoly Mirnics
      Biomolecules.2022; 12(10): 1535.     CrossRef
    • Myricitrin and Its Solid Lipid Nanoparticle Increase Insulin Secretion and Content of Isolated Islets from the Pancreas of Male Mice
      Akram Ahangarpour, Ali Akbar Oroojan
      Brazilian Journal of Pharmaceutical Sciences.2022;[Epub]     CrossRef
    • Diabetes and plant‐derived natural products: From ethnopharmacological approaches to their potential for modern drug discovery and development
      Arun K. Jugran, Sandeep Rawat, Hari P. Devkota, Indra D. Bhatt, Ranbeer S. Rawal
      Phytotherapy Research.2021; 35(1): 223.     CrossRef
    • Exploring brain insulin resistance in adults with bipolar depression using extracellular vesicles of neuronal origin
      Rodrigo B. Mansur, Francheska Delgado-Peraza, Mehala Subramaniapillai, Yena Lee, Michelle Iacobucci, Flora Nasri, Nelson Rodrigues, Joshua D. Rosenblat, Elisa Brietzke, Victoria E. Cosgrove, Nicole E. Kramer, Trisha Suppes, Charles L. Raison, Andrea Fagio
      Journal of Psychiatric Research.2021; 133: 82.     CrossRef
    • Protective Effects of Iridoid Glycoside from Corni Fructus on Type 2 Diabetes with Nonalcoholic Fatty Liver in Mice
      Dou Niu, Xue Chen, Ting Wang, Fuxing Wang, Qiusheng Zhang, Xiaochang Xue, Jiefang Kang, Dan Qian Chen
      BioMed Research International.2021; 2021: 1.     CrossRef
    • Microdose Lithium Protects against Pancreatic Islet Destruction and Renal Impairment in Streptozotocin-Elicited Diabetes
      Jiahui Zhang, Fnu Anshul, Deepak K. Malhotra, Juan Jaume, Lance D. Dworkin, Rujun Gong
      Antioxidants.2021; 10(1): 138.     CrossRef
    • p-Terphenyls From Aspergillus sp. GZWMJZ-055: Identification, Derivation, Antioxidant and α-Glycosidase Inhibitory Activities
      Yanchao Xu, Yong Wang, Dan Wu, Wenwen He, Liping Wang, Weiming Zhu
      Frontiers in Microbiology.2021;[Epub]     CrossRef
    • Updated Role of Neuropeptide Y in Nicotine-Induced Endothelial Dysfunction and Atherosclerosis
      Yan-li Zheng, Wan-da Wang, Mei-mei Li, Shu Lin, Hui-li Lin
      Frontiers in Cardiovascular Medicine.2021;[Epub]     CrossRef
    • IRS‐2/Akt/GSK‐3β/Nrf2 Pathway Contributes to the Protective Effects of Chikusetsu Saponin IVa against Lipotoxicity
      Lei Wang, Jialin Duan, Na Jia, Meiyou Liu, Shanshan Cao, Yan Weng, Wei Zhang, Jinyi Cao, Ruili Li, Jia Cui, Jingwen Wang, Silvana Hrelia
      Oxidative Medicine and Cellular Longevity.2021;[Epub]     CrossRef
    • In Vivo and In Vitro Assays Evaluating the Biological Activity of Taurine, Glucose and Energetic Beverages
      Marcos Mateo-Fernández, Fernando Valenzuela-Gómez, Rafael Font, Mercedes Del Río-Celestino, Tania Merinas-Amo, Ángeles Alonso-Moraga
      Molecules.2021; 26(8): 2198.     CrossRef
    • Effect of propolis on glycemic control in patients with type 2 diabetes: an updated systematic review and meta-analysis of randomized controlled trials
      Zahra Mosallanezhad, Cain Clark, Fatemeh Bahreini, Zahra Motamed, Abdolhamid Mosallanezhad, Seyedeh Fatemeh Hosseini, Aneseh Shaban-Khalaf, Zahra Sohrabi
      Nutrition & Food Science .2021; 51(7): 1124.     CrossRef
    • The Correlation between Selenium Dependent Glutathione Peroxidase Activity and Oxidant/Antioxidant Balance in Sera of Diabetic Patients with Nephropathy
      Abdulateef Altuhafi, Muhammed Altun, Mahmoud Hussein Hadwan
      Reports of Biochemistry and Molecular Biology.2021; 10(2): 164.     CrossRef
    • Effect of alpha-lipoic acid on oxidative stress parameters: A systematic review and meta-analysis
      Sanaz Rezaei Zonooz, Motahareh Hasani, Mojgan Morvaridzadeh, Ana Beatriz Pizarro, Hafez Heydari, Somaye Yosaee, Gholamreza Rezamand, Javad Heshmati
      Journal of Functional Foods.2021; 87: 104774.     CrossRef
    • The Mechanisms and Management of Age-Related Oxidative Stress in Male Hypogonadism Associated with Non-communicable Chronic Disease
      Kristian Leisegang, Shubhadeep Roychoudhury, Petr Slama, Renata Finelli
      Antioxidants.2021; 10(11): 1834.     CrossRef
    • Роль системы врождённого иммунитета и окислительного стресса в развитии сахарного диабета 1-типа. Пероксиредоксин 6 как новый антидиабетический препарат
      Е.Г. Новосёлова, О.В. Глушкова, М.О. Хренов, С.М. Лунин, Т.В. Новосёлова, С.Б. Парфенюк
      Биохимия.2021; 86(12): 1840.     CrossRef
    • Role of Innate Immunity and Oxidative Stress in the Development of Type 1 Diabetes Mellitus. Peroxiredoxin 6 as a New Anti-Diabetic Agent
      Elena G. Novoselova, Olga V. Glushkova, Maxim O. Khrenov, Sergey M. Lunin, Tatyana V. Novoselova, Svetlana B. Parfenuyk
      Biochemistry (Moscow).2021; 86(12-13): 1579.     CrossRef
    • Participation of Hsp70 and Hsp90α Heat Shock Proteins in Stress Response in the Course of Type 1 Diabetes Mellitus
      E. G. Novoselova, O. V. Glushkova, M. O. Khrenov, S. B. Parfenyuk, S. M. Lunin, T. V. Novoselova, E. E. Fesenko
      Doklady Biological Sciences.2020; 493(1): 124.     CrossRef
    • The correlation between blood oxidative stress and sialic acid content in diabetic patients with nephropathy, hypertension, and hyperlipidemia
      Sedigheh Shahvali, Armita Shahesmaeili, Mojgan Sanjari, Somayyeh Karami-Mohajeri
      Diabetology International.2020; 11(1): 19.     CrossRef
    • Green synthesis of gold nanoparticles from Fritillaria cirrhosa and its anti-diabetic activity on Streptozotocin induced rats
      Ying Guo, Nan Jiang, Li Zhang, Min Yin
      Arabian Journal of Chemistry.2020; 13(4): 5096.     CrossRef
    • The Role of Oxidative Stress in Physiopathology and Pharmacological Treatment with Pro- and Antioxidant Properties in Chronic Diseases
      Andrés García-Sánchez, Alejandra Guillermina Miranda-Díaz, Ernesto Germán Cardona-Muñoz
      Oxidative Medicine and Cellular Longevity.2020; 2020: 1.     CrossRef
    • Pharmacological and Advanced Cell Respiration Effects, Enhanced by Toxic Human-Bile Nano-Pharmaceuticals of Probucol Cell-Targeting Formulations
      Susbin Raj Wagle, Bozica Kovacevic, Daniel Walker, Corina Mihaela Ionescu, Melissa Jones, Goran Stojanovic, Sanja Kojic, Armin Mooranian, Hani Al-Salami
      Pharmaceutics.2020; 12(8): 708.     CrossRef
    • Triglyceride is independently correlated with insulin resistance and islet beta cell function: a study in population with different glucose and lipid metabolism states
      Minglei Ma, Haibin Liu, Jie Yu, Shuli He, Pingping Li, Chunxiao Ma, Huabing Zhang, Lingling Xu, Fan Ping, Wei Li, Qi Sun, Yuxiu Li
      Lipids in Health and Disease.2020;[Epub]     CrossRef
    • Protective Effects of Grape Seed Proanthocyanidins on the Kidneys of Diabetic Rats through the Nrf2 Signalling Pathway
      Yusong Ding, Haiyan Li, Yang Li, Dandan Liu, Liyuan Zhang, Tongling Wang, Tao Liu, Long Ma, Rocío De la Puerta
      Evidence-Based Complementary and Alternative Medicine.2020;[Epub]     CrossRef
    • The Role of CD36 in Type 2 Diabetes Mellitus: β-Cell Dysfunction and Beyond
      Jun Sung Moon, Udayakumar Karunakaran, Elumalai Suma, Seung Min Chung, Kyu Chang Won
      Diabetes & Metabolism Journal.2020; 44(2): 222.     CrossRef
    • Roles of Autophagy in Oxidative Stress
      Hyeong Rok Yun, Yong Hwa Jo, Jieun Kim, Yoonhwa Shin, Sung Soo Kim, Tae Gyu Choi
      International Journal of Molecular Sciences.2020; 21(9): 3289.     CrossRef
    • Antioxidant and prebiotic effects of a beverage composed by tropical fruits and yacon in alloxan-induced diabetic rats
      Ana Paula DIONISIO, Luciano Bruno de CARVALHO-SILVA, Nara Menezes VIEIRA, Nedio Jair WURLITZER, Ana Carolina da Silva PEREIRA, Maria de Fatima BORGES, Deborah dos Santos GARRUTI, Idila dos Santos ARAÚJO
      Food Science and Technology.2020; 40(1): 202.     CrossRef
    • Pro-oxidant–antioxidant balance (PAB) as a prognostic index in assessing the cardiovascular risk factors: A narrative review
      Hamideh Ghazizadeh, Maryam Saberi-Karimian, Maliheh Aghasizadeh, Reza Sahebi, Hamed Ghazavi, Hamed Khedmatgozar, Ameneh Timar, Mohadeseh Rohban, Ali Javandoost, Majid Ghayour-Mobarhan
      Obesity Medicine.2020; 19: 100272.     CrossRef
    • Rosemary Leaf Extract Inhibits Glycation, Breast Cancer Proliferation, and Diabetes Risks
      Yixiao Shen, Jing Han, Xiaoyan Zheng, Binling Ai, Yang Yang, Dao Xiao, Lili Zheng, Zhanwu Sheng
      Applied Sciences.2020; 10(7): 2249.     CrossRef
    • Trigonella stellata reduced the deleterious effects of diabetes mellitus through alleviation of oxidative stress, antioxidant- and drug-metabolizing enzymes activities
      Salah A. Sheweita, Sara A. ElHady, Hala M. Hammoda
      Journal of Ethnopharmacology.2020; 256: 112821.     CrossRef
    • A Shift Toward a Plant-Centered Diet From Young to Middle Adulthood and Subsequent Risk of Type 2 Diabetes and Weight Gain: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
      Yuni Choi, Nicole Larson, Daniel D. Gallaher, Andrew O. Odegaard, Jamal S. Rana, James M. Shikany, Lyn M. Steffen, David R. Jacobs
      Diabetes Care.2020; 43(11): 2796.     CrossRef
    • Ascorbic acid supplementation in type 2 diabetes mellitus
      Lipeng Shi, Xuqin Du, Pei Guo, Lumei Huang, Peng Qi, Qianhui Gong
      Medicine.2020; 99(45): e23125.     CrossRef
    • Analysis of the Effect of Fish Bars Made of Bilih Fish (Mystacoleuseus padangensis Blkr) Flour to Reduce Oxidative Stress in a Diabetic Rat Model
      Deni ELNOVRIZA, Hadi RIYADI, Rimbawan RIMBAWAN, Evy DAMAYANTHI, Adi WINARTO
      Journal of Nutritional Science and Vitaminology.2020; 66(Supplement): S36.     CrossRef
    • Antioxidant activity of crude ethanolic extract and fractions of Ziziphus mauritiana Lam. (Rhamnaceae) leaves from Burkina Faso
      Estelle N.H. Youl, Cyrille A.P. Ouédraogo, Moustapha Gambo, Moussa Ouédraogo, Martin Kiendrebéogo, Aristide Traoré, Innocent Pierre Guissou
      Journal of Basic and Clinical Physiology and Pharmacology.2019;[Epub]     CrossRef
    • CD36 dependent redoxosomes promotes ceramide-mediated pancreatic β-cell failure via p66Shc activation
      Udayakumar Karunakaran, Suma Elumalai, Jun Sung Moon, Kyu Chang Won
      Free Radical Biology and Medicine.2019; 134: 505.     CrossRef
    • Comparative proteomic analysis reveals drug resistance of Staphylococcus xylosus ATCC700404 under tylosin stress
      Xin Liu, Jinpeng Wang, Mo Chen, Ruixiang Che, Wenya Ding, Fei Yu, Yonghui Zhou, Wenqiang Cui, Xing Xiaoxu, Bello-Onaghise God’spower, Yanhua Li
      BMC Veterinary Research.2019;[Epub]     CrossRef
    • The Potential of Bilih Fish (Mystacoleuseus padangensis Blkr) Flour as a Zinc Source to Control Blood Glucose and Impact on Oxidative Stress in a Diabetic Rat Model
      Deni Elnovriza, Hadi Riyadi, Rimbawan ., Evy Damayanthi, Adi Winarto
      Pakistan Journal of Nutrition.2019; 18(3): 264.     CrossRef
    • Inflammaging and Oxidative Stress in Human Diseases: From Molecular Mechanisms to Novel Treatments
      Li Zuo, Evan R. Prather, Mykola Stetskiv, Davis E. Garrison, James R. Meade, Timotheus I. Peace, Tingyang Zhou
      International Journal of Molecular Sciences.2019; 20(18): 4472.     CrossRef
    • The variations of some salivary parameters as probable indices of the hereditary diabetes
      Menicagli Roberto, Marotta Ortensio
      International Journal of Preventive Medicine.2019; 10(1): 11.     CrossRef
    • The Interrelationship between Job Stress with the Immune System and Functional Memory of Women Working in Diagnostic Laboratories
      Mansoureh Sadeghi-Yarandi, Anahita Khodabakhshi-Koolaee, Mohammad Reza Falsafinejad, Neda Khaletbari
      The Neuroscience Journal of Shefaye Khatam.2019; 7(2): 23.     CrossRef
    • Effect of Cinnamon Administration on Fertility of Normal and Diabetic Male Rats
      Mahmoud Al-Shawabk, Abdulrahim Al Jamal
      Pakistan Journal of Nutrition.2019; 18(5): 491.     CrossRef
    • White Sesame Seed Oil Mitigates Blood Glucose Level, Reduces Oxidative Stress, and Improves Biomarkers of Hepatic and Renal Function in Participants with Type 2 Diabetes Mellitus
      Farhan Aslam, Sanaullah Iqbal, Muhammad Nasir, Aftab Ahmad Anjum
      Journal of the American College of Nutrition.2019; 38(3): 235.     CrossRef
    • Effect of combination of Gynura procumbens aqueous extract and Trigona spp. honey on fertility and libido of streptozotocin-induced hyperglycaemic male rats
      Khaidatul Akmar, MahanemMat Noor
      Asian Pacific Journal of Reproduction.2019; 8(2): 56.     CrossRef
    • Serum Antioxidant Parameters are Significantly Increased in Patients with Type 2 Diabetes Mellitus after Consumption of Chinese Propolis: A Randomized Controlled Trial Based on Fasting Serum Glucose Level
      Weina Gao, Lingling Pu, Jingyu Wei, Zhanxin Yao, Yawen Wang, Tala Shi, Liting Zhao, Changya Jiao, Changjiang Guo
      Diabetes Therapy.2018; 9(1): 101.     CrossRef
    • Baccharis trimera (Carqueja) Improves Metabolic and Redox Status in an Experimental Model of Type 1 Diabetes
      Natália Nogueira do Nascimento Kaut, Ana Carolina Silveira Rabelo, Glaucy Rodrigues Araujo, Jason Guy Taylor, Marcelo Eustáquio Silva, Maria Lúcia Pedrosa, Miriam Martins Chaves, Joamyr Victor Rossoni Junior, Daniela Caldeira Costa, Laura De Martino
      Evidence-Based Complementary and Alternative Medicine.2018;[Epub]     CrossRef
    • The Potential of South African Herbal Tisanes, Rooibos and Honeybush in the Management of Type 2 Diabetes Mellitus
      Olawale R. Ajuwon, Ademola O. Ayeleso, Gbenga A. Adefolaju
      Molecules.2018; 23(12): 3207.     CrossRef
    • Clinical variables and ethnicity may influenced by polymorphism of CAT −262C/T and MnSOD 47C/T antioxidant enzymes in Algerian type1 diabetes without complications
      A. Eddaikra, H. Amroun, R. Raache, A. Galleze, N. Abdallah-Elhadj, M. Azzouz, F. Meçabih, B. Mechti, M.C. Abbadi, C. Touil-Boukoffa, N. Attal
      Gene.2018; 670: 182.     CrossRef
    • Crystal structure and functional characterization of selenocysteine-containing glutathione peroxidase 4 suggests an alternative mechanism of peroxide reduction
      Astrid Borchert, Jacqueline Kalms, Sophia R. Roth, Marlena Rademacher, Andrea Schmidt, Hermann-Georg Holzhutter, Hartmut Kuhn, Patrick Scheerer
      Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids.2018; 1863(9): 1095.     CrossRef
    • The effects of green cardamom supplementation on blood glucose, lipids profile, oxidative stress, sirtuin-1 and irisin in type 2 diabetic patients: a study protocol for a randomized placebo-controlled clinical trial
      Mohadeseh Aghasi, Shohreh Ghazi-Zahedi, Fariba Koohdani, Fereydoun Siassi, Ensieh Nasli-Esfahani, Ali Keshavarz, Mostafa Qorbani, Hoorieh Khoshamal, Asma Salari-Moghaddam, Gity Sotoudeh
      BMC Complementary and Alternative Medicine.2018;[Epub]     CrossRef
    • Mice pancreatic islets protection from oxidative stress induced by single-walled carbon nanotubes through naringin
      A Ahangarpour, S Alboghobeish, AA Oroojan, MA Dehghani
      Human & Experimental Toxicology.2018; 37(12): 1268.     CrossRef
    • Chronic hyperglycemia mediated physiological alteration and metabolic distortion leads to organ dysfunction, infection, cancer progression and other pathophysiological consequences: An update on glucose toxicity
      Biplab Giri, Sananda Dey, Tanaya Das, Mrinmoy Sarkar, Jhimli Banerjee, Sandeep Kumar Dash
      Biomedicine & Pharmacotherapy.2018; 107: 306.     CrossRef
    • Cognitive dysfunction and metabolic comorbidities in mood disorders: A repurposing opportunity for glucagon-like peptide 1 receptor agonists?
      Rodrigo B. Mansur, Yena Lee, Mehala Subramaniapillai, Elisa Brietzke, Roger S. McIntyre
      Neuropharmacology.2018; 136: 335.     CrossRef
    • The protective effects of a novel synthetic β-elemene derivative on human umbilical vein endothelial cells against oxidative stress-induced injury: Involvement of antioxidation and PI3k/Akt/eNOS/NO signaling pathways
      Khalil Ali Ahmad, Hong Ze, Jichao Chen, Farhan Ullah Khan, Chen Xuezhuo, Jinyi Xu, Ding Qilong
      Biomedicine & Pharmacotherapy.2018; 106: 1734.     CrossRef
    • Curcumin alleviates liver oxidative stress in type 1 diabetic rats
      Zhenglu Xie, Binbin Wu, Guozhi Shen, Xiaqing Li, Qianying Wu
      Molecular Medicine Reports.2017;[Epub]     CrossRef
    • Treatment with a GLP−1R agonist over four weeks promotes weight loss-moderated changes in frontal-striatal brain structures in individuals with mood disorders
      Rodrigo B. Mansur, Andre Zugman, Juhie Ahmed, Danielle S. Cha, Mehala Subramaniapillai, Yena Lee, Julie Lovshin, Jung G. Lee, Jae-Hon Lee, Vladislav Drobinin, Jason Newport, Elisa Brietzke, Eva Z. Reininghaus, Kang Sim, Maj Vinberg, Natalie Rasgon, Tomas
      European Neuropsychopharmacology.2017; 27(11): 1153.     CrossRef
    • Plasma vascular endothelial growth factor B levels are increased in patients with newly diagnosed type 2 diabetes mellitus and associated with the first phase of glucose-stimulated insulin secretion function of β-cell
      J. Wu, H. Wei, H. Qu, Z. Feng, J. Long, Q. Ge, H. Deng
      Journal of Endocrinological Investigation.2017; 40(11): 1219.     CrossRef
    • Associations of Dietary Antioxidants and Risk of Type 2 Diabetes: Data from the 2007–2012 Korea National Health and Nutrition Examination Survey
      Dan Quansah, Kyungho Ha, Shinyoung Jun, Seong-Ah Kim, Sangah Shin, Gyung-Ah Wie, Hyojee Joung
      Molecules.2017; 22(10): 1664.     CrossRef
    • Curcumin attenuates oxidative stress in liver in Type 1 diabetic rats
      Zhenglu Xie, Xinqi Zeng, Xiaqing Li, Binbin Wu, Guozhi Shen, Qianying Wu, Changbiao Wu
      Open Life Sciences.2017; 12(1): 452.     CrossRef
    • Metabolic control and periodontal treatment decreases elevated oxidative stress in the early phases of type 1 diabetes onset
      Cüneyt A. Aral, Özlem Nalbantoğlu, Bilge G. Nur, Mustafa Altunsoy, Kübra Aral
      Archives of Oral Biology.2017; 82: 115.     CrossRef
    • Evaluation and Application of a Novel Quantitative Antioxidant Activity Assay Based on Cellular Metabolomics
      Jianteng Wei, Qingping Hu, Ningli Wang, Yewei Liu, Dong Pei, Duolong Di
      Chromatographia.2017; 80(4): 617.     CrossRef
    • C-X-C motif chemokine ligand 8 promotes endothelial cell homing via the Akt-signal transducer and activator of transcription pathway to accelerate healing of ischemic and hypoxic skin ulcers
      Lei Shen, Peng Zhang, Shanqiang Zhang, Liping Xie, Lijie Yao, Weiya Lang, Jie Lian, Wei Qin, Meng Zhang, Liang Ji
      Experimental and Therapeutic Medicine.2017; 13(6): 3021.     CrossRef
    • STEAP4: its emerging role in metabolism and homeostasis of cellular iron and copper
      Rachel T Scarl, C Martin Lawrence, Hannah M Gordon, Craig S Nunemaker
      Journal of Endocrinology.2017; 234(3): R123.     CrossRef
    • Current views on neuropeptide Y and diabetes-related atherosclerosis
      Wei-wei Sun, Ping Zhu, Yan-chuan Shi, Chen-liang Zhang, Xu-feng Huang, Shi-yu Liang, Zhi-yuan Song, Shu Lin
      Diabetes and Vascular Disease Research.2017; 14(4): 277.     CrossRef
    • Teucrium polium extract reverses symptoms of streptozotocin-induced diabetes in rats via rebalancing the Pdx1 and FoxO1 expressions
      Parvaneh Sadat Tabatabaie, Razieh Yazdanparast
      Biomedicine & Pharmacotherapy.2017; 93: 1033.     CrossRef
    • Morin activates the Nrf2-ARE pathway and reduces oxidative stress-induced DNA damage in pancreatic beta cells
      Pachamuthu Vanitha, Sankareswaran Senthilkumar, Sireesh Dornadula, Sundaramurthy Anandhakumar, Palanisamy Rajaguru, Kunka Mohanram Ramkumar
      European Journal of Pharmacology.2017; 801: 9.     CrossRef
    • Antioxidant status and gut microbiota change in an aging mouse model as influenced by exopolysaccharide produced by Lactobacillus plantarum YW11 isolated from Tibetan kefir
      Jian Zhang, Xiao Zhao, Yunyun Jiang, Wen Zhao, Ting Guo, Yongqiang Cao, Junwei Teng, Xiaona Hao, Juan Zhao, Zhennai Yang
      Journal of Dairy Science.2017; 100(8): 6025.     CrossRef
    • Metformin prevents glucotoxicity by alleviating oxidative and ER stress–induced CD36 expression in pancreatic beta cells
      Jun Sung Moon, Udayakumar Karunakaran, Suma Elumalai, In-Kyu Lee, Hyoung Woo Lee, Yong-Woon Kim, Kyu Chang Won
      Journal of Diabetes and its Complications.2017; 31(1): 21.     CrossRef
    • Differential dose-dependent Effects of Zinc Oxide Nanoparticles on Oxidative stress-mediated Pancreatic β-cell Death
      Swati C Asani, Rinku D Umrani, Kishore M Paknikar
      Nanomedicine.2017; 12(7): 745.     CrossRef
    • Effects of Silver Nanoparticles on Multiple Drug-Resistant Strains of Staphylococcus aureus and Pseudomonas aeruginosa from Mastitis-Infected Goats: An Alternative Approach for Antimicrobial Therapy
      Yu-Guo Yuan, Qiu-Ling Peng, Sangiliyandi Gurunathan
      International Journal of Molecular Sciences.2017; 18(3): 569.     CrossRef
    • Rac1-NADPH oxidase signaling promotes CD36 activation under glucotoxic conditions in pancreatic beta cells
      Suma Elumalai, Udayakumar Karunakaran, In Kyu Lee, Jun Sung Moon, Kyu Chang Won
      Redox Biology.2017; 11: 126.     CrossRef
    • Changes in pancreatic histology, insulin secretion and oxidative status in diabetic rats following treatment with Ficus deltoidea and vitexin
      Samsulrizal Nurdiana, Yong Meng Goh, Hafandi Ahmad, Sulaiman Md Dom, Nur Syimal’ain Azmi, Noor Syaffinaz Noor Mohamad Zin, Mahdi Ebrahimi
      BMC Complementary and Alternative Medicine.2017;[Epub]     CrossRef
    • Murraya paniculata(L.) (Orange Jasmine): Potential Nutraceuticals with Ameliorative Effect in Alloxan‐Induced Diabetic Rats
      Cicero Diego Almino Menezes, Francisca Adilfa de Oliveira Garcia, Glauce Socorro de Barros Viana, Patricia Gonçalves Pinheiro, Cícero Francisco Bezerra Felipe, Thaís Rodrigues de Albuquerque, Alisson Cordeiro Moreira, Enaide Soares Santos, Maynara Rodrigu
      Phytotherapy Research.2017; 31(11): 1747.     CrossRef
    • Exploiting biological activities of brown seaweed Ishige okamurae Yendo for potential industrial applications: a review
      K. K. Asanka Sanjeewa, Won Woo Lee, Jae-Il Kim, You-Jin Jeon
      Journal of Applied Phycology.2017; 29(6): 3109.     CrossRef
    • The thioredoxin and glutathione-dependent H2O2 consumption pathways in muscle mitochondria: Involvement in H2O2 metabolism and consequence to H2O2 efflux assays
      Daniel Munro, Sheena Banh, Emianka Sotiri, Nahid Tamanna, Jason R. Treberg
      Free Radical Biology and Medicine.2016; 96: 334.     CrossRef
    • Effect of crocin extracted from saffron on pro-oxidant–anti-oxidant balance in subjects with metabolic syndrome: A randomized, placebo-controlled clinical trial
      I. Nikbakht-Jam, M. Khademi, M. Nosrati, S. Eslami, M. Foroutan-Tanha, A. Sahebkar, S. Tavalaie, M. Ghayour-Mobarhan, G.A.A. Ferns, F. Hadizadeh, S.A.S. Tabassi, S.A. Mohajeri, M. Emamian
      European Journal of Integrative Medicine.2016; 8(3): 307.     CrossRef
    • Multicompartmental, multilayered probucol microcapsules for diabetes mellitus: Formulation characterization and effects on production of insulin and inflammation in a pancreatic β-cell line
      Armin Mooranian, Rebecca Negrulj, Frank Arfuso, Hani Al-Salami
      Artificial Cells, Nanomedicine, and Biotechnology.2016; 44(7): 1642.     CrossRef
    • Lipid peroxidation is associated with poor control of type-2 diabetes mellitus
      Sameer Hassan Fatani, Abdullatif Taha Babakr, EssamEldin Mohamed NourEldin, Abdalla A. Almarzouki
      Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2016; 10(2): S64.     CrossRef
    • Increased Electron Paramagnetic Resonance Signal Correlates with Mitochondrial Dysfunction and Oxidative Stress in an Alzheimer’s disease Mouse Brain
      Du Fang, Zhihua Zhang, Hang Li, Qing Yu, Justin T. Douglas, Anna Bratasz, Periannan Kuppusamy, Shirley ShiDu Yan, Hemachandra Reddy
      Journal of Alzheimer's Disease.2016; 51(2): 571.     CrossRef
    • Coffee silverskin extract improves glucose-stimulated insulin secretion and protects against streptozotocin-induced damage in pancreatic INS-1E beta cells
      Beatriz Fernandez-Gomez, Sonia Ramos, Luis Goya, María Dolores Mesa, María Dolores del Castillo, María Ángeles Martín
      Food Research International.2016; 89: 1015.     CrossRef
    • Male Subfertility Induced by Heterozygous Expression of Catalytically Inactive Glutathione Peroxidase 4 Is Rescued in Vivo by Systemic Inactivation of the Alox15 Gene
      Simone Hanna Brütsch, Marlena Rademacher, Sophia Regina Roth, Karin Müller, Susanne Eder, Dagmar Viertel, Christiane Franz, Hartmut Kuhn, Astrid Borchert
      Journal of Biological Chemistry.2016; 291(45): 23578.     CrossRef
    • Assessment of antioxidant activity, lipid profile, general biochemical and immune system responses of Wistar rats fed with dairy dessert containing Lactobacillus acidophilus La-5
      C.S. Moura, P.C.B. Lollo, P.N. Morato, E.A. Esmerino, L.P. Margalho, V.A. Santos-Junior, P.T. Coimbra, L.P. Cappato, M.C. Silva, A.S. Garcia-Gomes, D. Granato, H.M. A. Bolini, A.S. Sant'Ana, A.G. Cruz, Jaime Amaya-Farfan
      Food Research International.2016; 90: 275.     CrossRef
    • Discovery of biomarkers for oxidative stress based on cellular metabolomics
      Ningli Wang, Jianteng Wei, Yewei Liu, Dong Pei, Qingping Hu, Yu Wang, Duolong Di
      Biomarkers.2016; 21(5): 449.     CrossRef
    • Diabetic nephropathy and endothelial dysfunction: Current and future therapies, and emerging of vascular imaging for preclinical renal-kinetic study
      Wilson KC Leung, L Gao, Parco M Siu, Christopher WK Lai
      Life Sciences.2016; 166: 121.     CrossRef
    • Brazilian Green Propolis Improves Antioxidant Function in Patients with Type 2 Diabetes Mellitus
      Liting Zhao, Lingling Pu, Jingyu Wei, Jinghua Li, Jianquan Wu, Zhonghao Xin, Weina Gao, Changjiang Guo
      International Journal of Environmental Research and Public Health.2016; 13(5): 498.     CrossRef
    • Inhibition of Adenylyl Cyclase Type 5 Increases Longevity and Healthful Aging through Oxidative Stress Protection
      Stephen F. Vatner, Ronald E. Pachon, Dorothy E. Vatner
      Oxidative Medicine and Cellular Longevity.2015; 2015: 1.     CrossRef
    • Recent Breakthroughs in the Antioxidant and Anti-Inflammatory Effects of Morella and Myrica Species
      Bruno Silva, Ana Seca, Maria Barreto, Diana Pinto
      International Journal of Molecular Sciences.2015; 16(8): 17160.     CrossRef
    • Oxidative Stress Type Influences the Properties of Antioxidants Containing Polyphenols in RINm5F Beta Cells
      Nathalie Auberval, Stéphanie Dal, William Bietiger, Elodie Seyfritz, Jean Peluso, Christian Muller, Minjie Zhao, Eric Marchioni, Michel Pinget, Nathalie Jeandidier, Elisa Maillard, Valérie Schini-Kerth, Séverine Sigrist
      Evidence-Based Complementary and Alternative Medicine.2015; 2015: 1.     CrossRef
    • CD36 initiated signaling mediates ceramide-induced TXNIP expression in pancreatic beta-cells
      Udayakumar Karunakaran, Jun Sung Moon, Hyoung Woo Lee, Kyu Chang Won
      Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2015; 1852(11): 2414.     CrossRef
    • Free radicals and related reactive species as mediators of tissue injury and disease: implications for Health
      James P. Kehrer, Lars-Oliver Klotz
      Critical Reviews in Toxicology.2015; 45(9): 765.     CrossRef
    • Expression of Inactive Glutathione Peroxidase 4 Leads to Embryonic Lethality, and Inactivation of theAlox15Gene Does Not Rescue Such Knock-In Mice
      Simone Hanna Brütsch, Chi Chiu Wang, Lu Li, Hannelore Stender, Nilgün Neziroglu, Constanze Richter, Hartmut Kuhn, Astrid Borchert
      Antioxidants & Redox Signaling.2015; 22(4): 281.     CrossRef
    • Islet β-cell failure in type 2 diabetes – Within the network of toxic lipids
      Justyna Janikiewicz, Katarzyna Hanzelka, Kamil Kozinski, Katarzyna Kolczynska, Agnieszka Dobrzyn
      Biochemical and Biophysical Research Communications.2015; 460(3): 491.     CrossRef
    • Endoplasmic reticulum stress and Nrf2 repression in circulating cells of type 2 diabetic patients without the recommended glycemic goals
      C. Mozzini, U. Garbin, C. Stranieri, A. Pasini, E. Solani, I. A. Tinelli, L. Cominacini, A.M. Fratta Pasini
      Free Radical Research.2015; 49(3): 244.     CrossRef
    • El estrés oxidativo como predictor de longevidad; estudio de casos y controles
      Ángel Belenguer Varea, Kheira Mohamed Abdelaziz, Juan Antonio Avellana Zaragoza, Consuelo Borrás Blasco, Paula Sanchis Aguilar, José Viña Ribes
      Revista Española de Geriatría y Gerontología.2015; 50(1): 16.     CrossRef
    • Microbial phenolic metabolites improve glucose-stimulated insulin secretion and protect pancreatic beta cells against tert-butyl hydroperoxide-induced toxicity via ERKs and PKC pathways
      Elisa Fernández-Millán, Sonia Ramos, Carmen Alvarez, Laura Bravo, Luis Goya, María Ángeles Martín
      Food and Chemical Toxicology.2014; 66: 245.     CrossRef
    • Decreased serum CA19‐9 is associated with improvement of insulin resistance and metabolic control in patients with obesity and type 2 diabetes after Roux‐en‐Y gastric bypass
      Yinfang Tu, Haoyong Yu, Pin Zhang, Jianzhong Di, Xiaodong Han, Songhua Wu, Yuqian Bao, Weiping Jia
      Journal of Diabetes Investigation.2014; 5(6): 694.     CrossRef
    • Oxidative Stress Is Associated with an Increased Antioxidant Defense in Elderly Subjects: A Multilevel Approach
      Gemma Flores-Mateo, Roberto Elosua, Teresa Rodriguez-Blanco, Josep Basora-Gallisà, Mònica Bulló, Jordi Salas-Salvadó, Miguel Ángel Martínez-González, Ramon Estruch, Dolores Corella, Montserrat Fitó, Miquel Fiol, Fernando Arós, Enrique Gómez-Gracia, Isaac
      PLoS ONE.2014; 9(9): e105881.     CrossRef
    • Inflamed moods: A review of the interactions between inflammation and mood disorders
      Joshua D. Rosenblat, Danielle S. Cha, Rodrigo B. Mansur, Roger S. McIntyre
      Progress in Neuro-Psychopharmacology and Biological Psychiatry.2014; 53: 23.     CrossRef
    • Differences in pancreatic volume, fat content, and fat density measured by multidetector-row computed tomography according to the duration of diabetes
      Soo Lim, Jae Hyun Bae, Eun Ju Chun, Haeryoung Kim, So Yeon Kim, Kyoung Min Kim, Sung Hee Choi, Kyong Soo Park, Jose C. Florez, Hak Chul Jang
      Acta Diabetologica.2014; 51(5): 739.     CrossRef
    • Role of Lipid Peroxidation Products, Plasma Total Antioxidant Status, and Cu-, Zn-Superoxide Dismutase Activity as Biomarkers of Oxidative Stress in Elderly Prediabetics
      Sylwia Dzięgielewska-Gęsiak, Ewa Wysocka, Sławomir Michalak, Ewa Nowakowska-Zajdel, Teresa Kokot, Małgorzata Muc-Wierzgoń
      Oxidative Medicine and Cellular Longevity.2014; 2014: 1.     CrossRef
    • Inhibitors ofα-glucosidase andα-amylase fromCyperus rotundus
      Hong Hanh Thi Tran, Minh Chau Nguyen, Hoang Tram Le, Thi Luyen Nguyen, Thanh Binh Pham, Van Minh Chau, Hoai Nam Nguyen, Tien Dat Nguyen
      Pharmaceutical Biology.2014; 52(1): 74.     CrossRef
    • Diabetes Mellitus and Disturbances in Brain Connectivity: A Bidirectional Relationship?
      Rodrigo B. Mansur, Danielle S. Cha, Hanna O. Woldeyohannes, Joanna K. Soczynska, Andre Zugman, Elisa Brietzke, Roger S. McIntyre
      NeuroMolecular Medicine.2014; 16(4): 658.     CrossRef
    • Pathogenesis of Chronic Hyperglycemia: From Reductive Stress to Oxidative Stress
      Liang-Jun Yan
      Journal of Diabetes Research.2014; 2014: 1.     CrossRef
    • Vitamin C Protects against INS832/13 ^|^beta;-Cell Death and/or Dysfunction Caused by Glucolipotoxicity or 3T3-L1 Adipocyte Coculture
      Ruojun WANG, Jia LIU, Xiaoxuan GUO, Fengyi GAO, Baoping JI, Feng ZHOU
      Journal of Nutritional Science and Vitaminology.2014; 60(5): 313.     CrossRef
    • Antioxidant activities of novel small-molecule polysaccharide fractions purified from Portulaca oleracea L.
      Yu-Ping Li, Li-Hua Yao, Guan-Jie Wu, Xiao-Fang Pi, Yan-Chun Gong, Ruo-Shong Ye, Chen-Xi Wang
      Food Science and Biotechnology.2014; 23(6): 2045.     CrossRef
    • Anti-diabetic properties of a non-conventional radical scavenger, as compared to pioglitazone and exendin-4, in streptozotocin-nicotinamide diabetic mice
      Michela Novelli, Donatella Canistro, Manuela Martano, Niccola Funel, Andrea Sapone, Simone Melega, Matilde Masini, Vincenzo De Tata, Anna Pippa, Cecilia Vecoli, Daniela Campani, Rocco De Siena, Antonio Soleti, Moreno Paolini, Pellegrino Masiello
      European Journal of Pharmacology.2014; 729: 37.     CrossRef
    • Therapeutic Roles of Heme Oxygenase-1 in Metabolic Diseases: Curcumin and Resveratrol Analogues as Possible Inducers of Heme Oxygenase-1
      Yong Son, Ju Hwan Lee, Hun-Taeg Chung, Hyun-Ock Pae
      Oxidative Medicine and Cellular Longevity.2013; 2013: 1.     CrossRef
    • Endoplasmic Reticulum Oxidoreductin-1α (Ero1α) Improves Folding and Secretion of Mutant Proinsulin and Limits Mutant Proinsulin-induced Endoplasmic Reticulum Stress
      Jordan Wright, Julia Birk, Leena Haataja, Ming Liu, Thomas Ramming, Michael A. Weiss, Christian Appenzeller-Herzog, Peter Arvan
      Journal of Biological Chemistry.2013; 288(43): 31010.     CrossRef
    • Moving on from GWAS: Functional Studies on the G6PC2 Gene Implicated in the Regulation of Fasting Blood Glucose
      Richard M. O’Brien
      Current Diabetes Reports.2013; 13(6): 768.     CrossRef

    • PubReader PubReader
    • Cite this Article
      Cite this Article
      export Copy Download
      Close
      Download Citation
      Download a citation file in RIS format that can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Reference Manager.

      Format:
      • RIS — For EndNote, ProCite, RefWorks, and most other reference management software
      • BibTeX — For JabRef, BibDesk, and other BibTeX-specific software
      Include:
      • Citation for the content below
      A Systematic Review of Oxidative Stress and Safety of Antioxidants in Diabetes: Focus on Islets and Their Defense
      Diabetes Metab J. 2013;37(2):106-112.   Published online April 16, 2013
      Close
    • XML DownloadXML Download
    Figure
    • 0
    • 1
    A Systematic Review of Oxidative Stress and Safety of Antioxidants in Diabetes: Focus on Islets and Their Defense
    Image Image
    Fig. 1 Current working model of reactive oxygen species (ROS) generation via hyperglycemia, free fatty acids, and cytokines. Excess generation of mitochondrial ROS activates stress sensitive pathways including polyol, advanced glycation end products (AGEs), protein kinase C (PKC), and hexosamine flux. Detailed mechanisms are discussed in the text of the present study. NF-κB, nuclear factor kappa B; JNK, c-Jun N-terminal kinases; JAK, Janus kinase; STAT, signal transducer and activator of transcription.
    Fig. 2 Proposed causative link of β-cell dysfunction between reactive oxygen species (ROS) and antioxidants. In the proposed mechanism, glucose stimulates intracellular ROS generation, which leads to glucose stimulated insulin secretion (GSIS). Likewise, chronic exposure to free radicals leads to β-cell dysfunction and death. Administration of dietary antioxidants may inhibit free radical induced cell dysfunction; however, they may also interfere with glucose induced ROS signaling in GSIS. SOD, superoxide dismutase; GPx, glutathione peroxidase; Nrf2, nuclear factor erythroid 2-related factor 2.
    A Systematic Review of Oxidative Stress and Safety of Antioxidants in Diabetes: Focus on Islets and Their Defense
    Karunakaran U, Park KG. A Systematic Review of Oxidative Stress and Safety of Antioxidants in Diabetes: Focus on Islets and Their Defense. Diabetes Metab J. 2013;37(2):106-112.
    DOI: https://doi.org/10.4093/dmj.2013.37.2.106.

    Diabetes Metab J : Diabetes & Metabolism Journal
    Close layer
    TOP