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A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 32102

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Prof. Dr. Vanessa Routh

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Department of Pharmacology, Physiology & Neuroscience, Medical Science Building (MSB), 185 South Orange Avenue, Room I 681, Newark, NJ 07101, USA
Interests: metabolism; glucose metabolism; insulin signaling; reactive oxygen species; neuroendocrinology; metabolic diseases
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Dr. Xavier Fioramonti

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Institut National de la Recherche Agronomique, Université de Bordeaux, Bordeaux INP, NutriNeuro, UMR 1286, F-33000 Bordeaux, France
Interests: metabolic diseases; diabetes; obesity
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Special Issue Information

Dear colleagues,

Oxidative stress is a major contributing factor in the pathology of diabetes mellitus. Diabetic hyperglycemia increases inflammatory markers and reactive oxygen species (ROS) production in peripheral tissues and in the brain. Recurrent hypoglycemia, which occurs in patients with Type 1 and advanced Type 2 diabetes mellitus that are using intensive insulin therapy, also increases ROS levels. Increased ROS levels and oxidative stress compromise endogenous antioxidant pathways. Furthermore, recent studies point to the therapeutic value of antioxidants in ameliorating diabetic complications.

We invite you to submit your latest research findings or a review to this Special issue which will bring together current research regarding the role of oxidative stress and antioxidants in the pathology of diabetes mellitus. This research can include both in vitro and in vivo studies relating to any of the following topics: mechanisms underlying hyper- or hypoglycemia-induced oxidative stress, the role of oxidative stress in diabetic complications including, but not limited to, central and peripheral nervous system, cardiovascular, pancreatic, endothelial and renal dysfunction or psychological disorders, and the role of both endogenous and exogenous antioxidants in Type 1 and Type 2 diabetes mellitus. Nutritional approaches aiming at decreasing oxidative stress and improving blood glucose levels or diabetes-associated complications are welcome.

Prof. Dr. Vanessa Routh
Dr. Xavier Fioramonti
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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Research

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16 pages, 1957 KiB

Open AccessArticle

Randomized Clinical Trial of How Long-Term Glutathione Supplementation Offers Protection from Oxidative Damage and Improves HbA1c in Elderly Type 2 Diabetic Patients

by Saurabh Kalamkar, Jhankar Acharya, Arjun Kolappurath Madathil, Vijay Gajjar, Uma Divate, Sucheta Karandikar-Iyer, Pranay Goel and Saroj Ghaskadbi

Antioxidants 2022, 11(5), 1026; https://doi.org/10.3390/antiox11051026 - 23 May 2022

Cited by 15 | Viewed by 6547

Abstract

Complications in type 2 diabetes (T2D) arise from hyperglycemia-induced oxidative stress. Here, we examined the effectiveness of supplementation with the endogenous antioxidant glutathione (GSH) during anti-diabetic treatment. A total of 104 non-diabetic and 250 diabetic individuals on anti-diabetic therapy, of either sex and aged between 30 and 78 years, were recruited. A total of 125 diabetic patients were additionally given 500 mg oral GSH supplementation daily for a period of six months. Fasting and PP glucose, insulin, HbA1c, GSH, oxidized glutathione (GSSG), and 8-hydroxy-2-deoxy guanosine (8-OHdG) were measured upon recruitment and after three and six months of supplementation. Statistical significance and effect size were assessed longitudinally across all arms. Blood GSH increased (Cohen’s d = 1.01) and 8-OHdG decreased (Cohen’s d = −1.07) significantly within three months (p < 0.001) in diabetic individuals. A post hoc sub-group analysis showed that HbA1c (Cohen’s d = −0.41; p < 0.05) and fasting insulin levels (Cohen’s d = 0.56; p < 0.05) changed significantly in diabetic individuals above 55 years. GSH supplementation caused a significant increase in blood GSH and helped maintain the baseline HbA1c overall. These results suggest GSH supplementation is of considerable benefit to patients above 55 years, not only supporting decreased glycated hemoglobin (HbA1c) and 8-OHdG but also increasing fasting insulin. The clinical implication of our study is that the oral administration of GSH potentially complements anti-diabetic therapy in achieving better glycemic targets, especially in the elderly population. Full article

(This article belongs to the Special Issue Antioxidants in Diabetes)

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19 pages, 3501 KiB

Open AccessArticle

Antioxidative, Antidiabetic, and Hypolipidemic Properties of Probiotic-Enriched Fermented Camel Milk Combined with Salvia officinalis Leaves Hydroalcoholic Extract in Streptozotocin-Induced Diabetes in Rats

by Yousef M. Alharbi, Sally S. Sakr, Saleh M. Albarrak, Tariq I. Almundarij, Hassan Barakat and Mohamed F. Y. Hassan

Antioxidants 2022, 11(4), 668; https://doi.org/10.3390/antiox11040668 - 30 Mar 2022

Cited by 14 | Viewed by 3196

Abstract

Antioxidative, antidiabetic, and hypolipidemic properties of probiotic-enriched fermented camel milk (FCM) combined with Salvia officinalis L. leaves hydroalcoholic extract (SOHE) in streptozotocin-induced diabetes in rats were investigated. Phytochemicals analysis and antioxidant capacity indicated that S. officinalis contained high phenolics with super antioxidant activity. Subsequently, HPLC analysis demonstrated 13 phenolic acids and 14 flavonoids in considerable amounts with ferulic acid and resveratrol as predominant, respectively. The antidiabetic and hypolipidemic properties of FCM and SOHE were examined in a designed animal model consisting of seven treated groups for four weeks. There was a negative group (G1); the positive group (G2) received a single dose (50 mg kg⁻¹) of streptozotocin (STZ) by intraperitoneal injection (i.p.); in G3, diabetic rats (DRs) orally received 5 mL FCM kg⁻¹ daily; in G4, DRs orally received 50 mg GAE SOHE kg⁻¹ daily; in G5, DRs orally received 5 mL FCM contains 25 mg GAE SOHE kg⁻¹ daily; in G6, DRs orally received 5 mL FCM contains 50 mg GAE SOHE kg⁻¹ daily; in G7, DRs orally received 50 mg metformin kg⁻¹ daily. Combining FCM with SOHE at 25 or 50 mg kg⁻¹ exhibited a synergistic effect in significantly lowering random blood glucose (RBG), fasting blood glucose (FBG), and improved weight gain recovery %. The hypolipidemic effect of FCM + 50 mg GAE SOHE kg⁻¹ was significantly higher than using FCM or SOHE individually, and attenuation in triglycerides (TG), total cholesterol (CHO), and high- and low-density lipoproteins (HDL and LDL), and very-low-density lipoproteins (VLDL) was remarked. Combining FCM with SOHE at 25 or 50 mg kg⁻¹ ameliorated liver and kidney functions better than individual uses of FCM, SOHE, or metformin. Interestingly, FCM with 50 mg SOHE kg⁻¹ presented significant improvement in the activity of antioxidant enzymes, reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and a substantial reduction in malonaldehyde (MDA) levels with 53.75%, 89.93%, 63.06%, and 58.69% when compared to the STZ group (G2), respectively. Histopathologically, administrating FCM + 25, 50 mg SOHE kg⁻¹ or 50 mg kg⁻¹ metformin showed a normal histological structure of both islets of Langerhans cells and acini. In conclusion, combining FCM with SOHE presented synergistic and therapeutical efficacy. It could be beneficial and profitable for controlling diabetes mellitus complications and protecting against oxidative stress. Full article

(This article belongs to the Special Issue Antioxidants in Diabetes)

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22 pages, 4345 KiB

Open AccessArticle

Inhibition Mechanism of Components Isolated from Morus alba Branches on Diabetes and Diabetic Complications via Experimental and Molecular Docking Analyses

by Ryeong-Ha Kwon, Niha Thaku, Binod Timalsina, Se-Eun Park, Jae-Sue Choi and Hyun-Ah Jung

Antioxidants 2022, 11(2), 383; https://doi.org/10.3390/antiox11020383 - 14 Feb 2022

Cited by 11 | Viewed by 3075

Abstract

Previously, we reported the anti-diabetic effect of Morus alba root bark and the compounds therein. In our continuous study of other parts of this plant, the ability of the branch of Morus alba to inhibit α-glucosidase, protein tyrosine phosphatase 1B (PTP1B), and advanced glycation end products (AGEs) formation was evaluated. Moreover, there are no previous studies that have performed enzyme kinetics and molecular docking analyses, along with assessments of peroxynitrite (ONOO⁻) inhibitory activities. Since the Morus alba branch exhibited favorable inhibitory effects, repeated column chromatography was performed to obtain eight compounds, including four flavonoids (1, 3, 6, 8), one arylbenzofuran (2), one stilbene (5), one Diels–Alder-type adduct (7), and one sterol (4). Among them, compounds 1–3 and 5–7 were mixed-type inhibitors of α-glucosidase, sharing the same catalytic residues with acarbose and the same allosteric sites with (Z)-3-bytylidenephthalide. On the other hand, kuwanon C (1) and oxyresveratrol (5) interacted with residues of the allosteric site (α3 and α6 helices) of PTP1B, indicating their use as non-competitive inhibitors. Interestingly, kuwanon G (7) directly bound the catalytic site, or interrupted the binding between the substrate and the active site, as a mixed-type inhibitor. Moreover, most of the compounds exhibited greater activity against AGE formation and ONOO⁻ than positive controls. The IC₅₀ values required to inhibit ONOO⁻ using compounds 1, 3, 5, 6, and 7 were reported for the first time, and range from 1.08 to 12.92 μM. Based on the structure–activity relationship, the presence of hydroxyl, resorcinol, and prenyl moieties was important in the prevention of diabetes’ pathological mechanisms, and these findings have been further supported by molecular docking analysis. These computational and experimental results will be useful in the development of therapeutic candidates to prevent/treat diabetes and its complications. Full article

(This article belongs to the Special Issue Antioxidants in Diabetes)

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18 pages, 1555 KiB

Open AccessArticle

Effects of a 12-Month Treatment with Glucagon-like Peptide-1 Receptor Agonists, Sodium-Glucose Cotransporter-2 Inhibitors, and Their Combination on Oxidant and Antioxidant Biomarkers in Patients with Type 2 Diabetes

by Vaia Lambadiari, John Thymis, Dimitris Kouretas, Zoi Skaperda, Fotios Tekos, Foteini Kousathana, Aikaterini Kountouri, Konstantinos Balampanis, John Parissis, Ioanna Andreadou, Maria Tsoumani, Christina Chania, Konstantinos Katogiannis, George Dimitriadis, Aristotelis Bamias and Ignatios Ikonomidis

Antioxidants 2021, 10(9), 1379; https://doi.org/10.3390/antiox10091379 - 28 Aug 2021

Cited by 18 | Viewed by 3004

Abstract

Imbalance between oxidative stress burden and antioxidant capacity is implicated in the course of atherosclerosis among type 2 diabetic patients. We addressed the effects of insulin, glucagon-like peptide-1 receptor agonists (GLP1-RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), and their combination on levels of oxidant and antioxidant biomarkers. We recruited a total of 160 type 2 diabetics, who received insulin (n = 40), liraglutide (n = 40), empagliflozin (n = 40), or their combination (GLP-1RA+SGLT-2i) (n = 40). We measured at baseline, at 4 and at 12 months of treatment: (a) Thiobarbituric Acid Reactive Substances (TBARS), (b) Malondialdehyde (MDA), (c) Reducing Power (RP), (d) 2,2¢-azino-bis-(3-ethylbenzthiazoline-6-sulphonic acid) radical (ABTS) and (e) Total Antioxidant Capacity TAC). Dual treatment resulted in significant improvement of TBARS, MDA, and ABTS at four months compared with the other groups (p < 0.05 for all comparisons). At twelve months, all participants improved TBARS, MDA, and ABTS (p < 0.05). At 12 months, GLP1-RA and GLP-1RA+SGLT2-i provided a greater reduction of TBARS (−8.76% and −9.83%) compared with insulin or SGLT2i (−0.5% and 3.22%), (p < 0.05). GLP1-RA and GLP-1RA+SGLT-2i showed a greater reduction of MDA (−30.15% and −31.44%) compared with insulin or SGLT2i (4.72% and −3.74%), (p < 0.05). SGLT2i and GLP-1RA+SGLT2-i showed increase of ABTS (12.87% and 14.13%) compared with insulin or GLP1-RA (2.44% and −3.44%), (p < 0.05). Only combined treatment resulted in increase of TAC compared with the other groups after 12 months of treatment (p < 0.05).12-month treatment with GLP1-RA and SGLT2i resulted in reduction of biomarkers responsible for oxidative modifications and increase of antioxidant biomarker, respectively. The combination treatment was superior and additive to each separate agent and also the beneficial effects appeared earlier. Full article

(This article belongs to the Special Issue Antioxidants in Diabetes)

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12 pages, 1308 KiB

Open AccessArticle

β-Hydroxybutyrate, a Ketone Body, Potentiates the Antioxidant Defense via Thioredoxin 1 Upregulation in Cardiomyocytes

by Shin-ichi Oka, Fan Tang, Adave Chin, Guersom Ralda, Xiaoyong Xu, Chengchen Hu, Zhi Yang, Maha Abdellatif and Junichi Sadoshima

Antioxidants 2021, 10(7), 1153; https://doi.org/10.3390/antiox10071153 - 20 Jul 2021

Cited by 13 | Viewed by 3815

Abstract

Thioredoxin 1 (Trx1) is a major antioxidant that acts adaptively to protect the heart during the development of diabetic cardiomyopathy. The molecular mechanism(s) responsible for regulating the Trx1 level and/or activity during diabetic cardiomyopathy is unknown. β-hydroxybutyrate (βHB), a major ketone body in mammals, acts as an alternative energy source in cardiomyocytes under stress, but it also appears to be involved in additional mechanisms that protect the heart against stress. βHB upregulated Trx1 in primary cultured cardiomyocytes in a dose- and a time-dependent manner and a ketogenic diet upregulated Trx1 in the heart. βHB protected cardiomyocytes against H₂O₂-induced death, an effect that was abolished in the presence of Trx1 knockdown. βHB also alleviated the H₂O₂-induced inhibition of mTOR and AMPK, known targets of Trx1, in a Trx1-dependent manner, suggesting that βHB potentiates Trx1 function. It has been shown that βHB is a natural inhibitor of HDAC1 and knockdown of HDAC1 upregulated Trx1 in cardiomyocytes, suggesting that βHB may upregulate Trx1 through HDAC inhibition. βHB induced Trx1 acetylation and inhibited Trx1 degradation, suggesting that βHB-induced inhibition of HDAC1 may stabilize Trx1 through protein acetylation. These results suggest that βHB potentiates the antioxidant defense in cardiomyocytes through the inhibition of HDAC1 and the increased acetylation and consequent stabilization of Trx1. Thus, modest upregulation of ketone bodies in diabetic hearts may protect the heart through the upregulation of Trx1. Full article

(This article belongs to the Special Issue Antioxidants in Diabetes)

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22 pages, 3675 KiB

Open AccessArticle

Central Acting Hsp10 Regulates Mitochondrial Function, Fatty Acid Metabolism, and Insulin Sensitivity in the Hypothalamus

by Kristina Wardelmann, Michaela Rath, José Pedro Castro, Sabine Blümel, Mareike Schell, Robert Hauffe, Fabian Schumacher, Tanina Flore, Katrin Ritter, Andreas Wernitz, Toru Hosoi, Koichiro Ozawa, Burkhard Kleuser, Jürgen Weiß, Annette Schürmann and André Kleinridders

Antioxidants 2021, 10(5), 711; https://doi.org/10.3390/antiox10050711 - 30 Apr 2021

Cited by 13 | Viewed by 3983

Abstract

Mitochondria are critical for hypothalamic function and regulators of metabolism. Hypothalamic mitochondrial dysfunction with decreased mitochondrial chaperone expression is present in type 2 diabetes (T2D). Recently, we demonstrated that a dysregulated mitochondrial stress response (MSR) with reduced chaperone expression in the hypothalamus is an early event in obesity development due to insufficient insulin signaling. Although insulin activates this response and improves metabolism, the metabolic impact of one of its members, the mitochondrial chaperone heat shock protein 10 (Hsp10), is unknown. Thus, we hypothesized that a reduction of Hsp10 in hypothalamic neurons will impair mitochondrial function and impact brain insulin action. Therefore, we investigated the role of chaperone Hsp10 by introducing a lentiviral-mediated Hsp10 knockdown (KD) in the hypothalamic cell line CLU-183 and in the arcuate nucleus (ARC) of C57BL/6N male mice. We analyzed mitochondrial function and insulin signaling utilizing qPCR, Western blot, XF96 Analyzer, immunohistochemistry, and microscopy techniques. We show that Hsp10 expression is reduced in T2D mice brains and regulated by leptin in vitro. Hsp10 KD in hypothalamic cells induced mitochondrial dysfunction with altered fatty acid metabolism and increased mitochondria-specific oxidative stress resulting in neuronal insulin resistance. Consequently, the reduction of Hsp10 in the ARC of C57BL/6N mice caused hypothalamic insulin resistance with acute liver insulin resistance. Full article

(This article belongs to the Special Issue Antioxidants in Diabetes)

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17 pages, 1961 KiB

Open AccessArticle

Analysis of Lipid Peroxidation by UPLC-MS/MS and Retinoprotective Effects of the Natural Polyphenol Pterostilbene

by Isabel Torres-Cuevas, Iván Millán, Miguel Asensi, Máximo Vento, Camille Oger, Jean-Marie Galano, Thierry Durand and Ángel L. Ortega

Antioxidants 2021, 10(2), 168; https://doi.org/10.3390/antiox10020168 - 23 Jan 2021

Cited by 9 | Viewed by 2431

Abstract

The loss of redox homeostasis induced by hyperglycemia is an early sign and key factor in the development of diabetic retinopathy. Due to the high level of long-chain polyunsaturated fatty acids, diabetic retina is highly susceptible to lipid peroxidation, source of pathophysiological alterations in diabetic retinopathy. Previous studies have shown that pterostilbene, a natural antioxidant polyphenol, is an effective therapy against diabetic retinopathy development, although its protective effects on lipid peroxidation are not well known. Plasma, urine and retinas from diabetic rabbits, control and diabetic rabbits treated daily with pterostilbene were analyzed. Lipid peroxidation was evaluated through the determination of derivatives from arachidonic, adrenic and docosahexaenoic acids by ultra-performance liquid chromatography coupled with tandem mass spectrometry. Diabetes increased lipid peroxidation in retina, plasma and urine samples and pterostilbene treatment restored control values, showing its ability to prevent early and main alterations in the development of diabetic retinopathy. Through our study, we are able to propose the use of a derivative of adrenic acid, 17(RS)-10-epi-SC-Δ¹⁵-11-dihomo-IsoF, for the first time, as a suitable biomarker of diabetic retinopathy in plasmas or urine. Full article

(This article belongs to the Special Issue Antioxidants in Diabetes)

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Review

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15 pages, 1334 KiB

Open AccessReview

An Overview on the Therapeutic Function of Foods Enriched with Plant Sterols in Diabetes Management

by Selvaraj Jayaraman, Anitha Roy, Srinivasan Vengadassalapathy, Ramya Sekar, Vishnu Priya Veeraraghavan, Ponnulakshmi Rajagopal, Gayathri Rengasamy, Raktim Mukherjee, Durairaj Sekar and Reji Manjunathan

Antioxidants 2021, 10(12), 1903; https://doi.org/10.3390/antiox10121903 - 27 Nov 2021

Cited by 5 | Viewed by 3975

Abstract

Diabetes is one of the most significant health issues across the world. People identified with diabetes are more vulnerable to various infections and are at a greater risk of developing cardiovascular diseases. The plant-based food we consume often contains many sterol-based bioactive compounds. It is well documented that these compounds could effectively manage the processes of insulin metabolism and cholesterol regulation. Insulin resistance followed by hyperglycemia often results in oxidative stress level enhancement and increased reactive oxygen species production. At the molecular level, these changes induce apoptosis in pancreatic cells and hence lead to insulin insufficiency. Studies have proved that plant sterols can lower inflammatory and oxidative stress damage connected with DNA repair mechanisms. The effective forms of phyto compounds are polyphenols, terpenoids, and thiols abundant in vegetables, fruits, nuts, and seeds. The available conventional drug-based therapies for the prevention and management of diabetes are time-consuming, costly, and with life-threatening side effects. Thereby, the therapeutic management of diabetes with plant sterols available in our daily diet is highly welcome as there are no side effects. This review intends to offer an overview of the present scenario of the anti-diabetic compounds from food ingredients towards the therapeutic beneficial against diabetes. Full article

(This article belongs to the Special Issue Antioxidants in Diabetes)

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