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Antioxidants
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Antioxidant Defence in Type 2 Diabetes
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Antioxidant Defence in Type 2 Diabetes

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 (25 March 2022) | Viewed by 16097

Special Issue Editors

Dr. Kenneth A. Earle

E-Mail Website
Guest Editor
Institute of Medical and Biomedical Education, St George’s University of London, London SW17 0QT, UK
Interests: Type 2 diabetes; oxidative stress; antioxidants; glutathione peroxidase; sex differences; cardiovascular risk
Dr. Karima Zitouni

E-Mail Website
Guest Editor
Institute of Medical and Biomedical Education, St George’s University of London, London SW17 0QT, UK
Interests: antioxidants; antioxidant activity; free radicals; free radical scavengers; lipid peroxidation; oxidative stress biomarkers

Special Issue Information

Dear Colleagues,

The pandemic of diabetes mellitus continues to grow and challenge health service provision due to the morbidity from microvascular complications and premature death from cardiovascular disease. 

Over the past decade, Cardiovascular Outcome (CVOT) trials of the newer classes of agents (sodium glucose transporter-2 inhibitors and glucagon-like polypeptide receptor agonists) used in the treatment of type 2 diabetes have shown benefit in reducing vascular complications. Recent studies suggest that these effects are associated with an amelioration of oxidative stress. 

An established and strong experimental evidence base exists for a role of oxidative stress in key target tissues in the onset of diabetes and the development of its complications. However, clinical data concerning the effect of antioxidant therapy in preventing micro- and macrovascular disease is conflicting in general but also compelling in some selected, sub-groups of patients with type 2 diabetes.  

The current COVID-19 pandemic has revealed that the higher risk of severe disease occurs in certain patient groups. These include those with type 2 diabetes, who are overweight, are of non-Caucasian heritage or from deprived socio-economic backgrounds. A hypothesis is emerging that in groups characterized as having higher insulin-resistance, severe disease is linked to an over-exuberance or deficiency of antioxidant defence. It is an aim of future research that modulation of host antioxidant pathways will help in the development of targeted treatment for diabetic vasculopathy.

Dr. Kenneth A. Earle
Dr. Karima Zitouni
Guest Editors

Manuscript Submission Information

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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.

Keywords

  • Type 2 diabetes
  • Antioxidant defence
  • Oxidative stress

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Published Papers (4 papers)

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Research

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18 pages, 5850 KiB  
Article
N-Acetylcysteine Enhances the Recovery of Ischemic Limb in Type-2 Diabetic Mice
by Qiang Zhu, Xuanyou Liu, Qingyi Zhu, Zehao Liu, Chunlin Yang, Hao Wu, Linfang Zhang, Xiujuan Xia, Meifang Wang, Hong Hao, Yuqi Cui, Guangsen Zhang, Michael A. Hill, Gregory C. Flaker, Shenghua Zhou and Zhenguo Liu
Antioxidants 2022, 11(6), 1097; https://doi.org/10.3390/antiox11061097 - 31 May 2022
Cited by 7 | Viewed by 3016
Abstract
Critical limb ischemia (CLI) is a severe complication of diabetes mellitus that occurs without effective therapy. Excessive reactive oxygen species (ROS) production and oxidative stress play critical roles in the development of diabetic cardiovascular complications. N-acetylcysteine (NAC) reduces ischemia-induced ROS production. The [...] Read more.
Critical limb ischemia (CLI) is a severe complication of diabetes mellitus that occurs without effective therapy. Excessive reactive oxygen species (ROS) production and oxidative stress play critical roles in the development of diabetic cardiovascular complications. N-acetylcysteine (NAC) reduces ischemia-induced ROS production. The present study aimed to investigate the effect of NAC on the recovery of ischemic limb in an experimental model of type-2 diabetes. TALLYHO/JngJ diabetic and SWR/J non-diabetic mice were used for developing a CLI model. For NAC treatment, mice received NAC (1 mg/mL) in their drinking water for 24 h before initiating CLI, and continuously for the duration of the experiment. Blood flow, mechanical function, histology, expression of antioxidant enzymes including superoxide dismutase (SOD)-1, SOD-3, glutathione peroxidase (Gpx)-1, catalase, and phosphorylated insulin receptor substrate (IRS)-1, Akt, and eNOS in ischemic limb were evaluated in vivo or ex vivo. Body weight, blood glucose, plasma advanced glycation end-products (AGEs), plasma insulin, insulin resistance index, and plasma TNF-a were also evaluated during the experiment. NAC treatment effectively attenuated ROS production with preserved expressions of SOD-1, Gpx-1, catalase, phosphorylated Akt, and eNOS, and enhanced the recovery of blood flow and function of the diabetic ischemic limb. NAC treatment also significantly decreased the levels of phosphorylated IRS-1 (Ser307) expression and plasma TNF-α in diabetic mice without significant changes in blood glucose and AGEs levels. In conclusion, NAC treatment enhanced the recovery of blood flow and mechanical function in ischemic limbs in T2D mice in association with improved tissue redox/inflammatory status and insulin resistance. Full article
(This article belongs to the Special Issue Antioxidant Defence in Type 2 Diabetes)
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17 pages, 6218 KiB  
Article
Combination Effects of Metformin and a Mixture of Lemon Balm and Dandelion on High-Fat Diet-Induced Metabolic Alterations in Mice
by Jae Young Choi, Tae-Woo Jang, Phil Hyun Song, Seong Hoon Choi, Sae-Kwang Ku and Chang-Hyun Song
Antioxidants 2022, 11(3), 580; https://doi.org/10.3390/antiox11030580 - 18 Mar 2022
Cited by 4 | Viewed by 3345
Abstract
Metformin, the first-line drug for type 2 diabetes mellitus (T2DM), has additional effects on improvements of nonalcoholic fatty liver disease (NAFLD); however, there are no treatments for both T2DM and NAFLD. Previous studies have shown hepatoprotective effects of a mixture of lemon balm [...] Read more.
Metformin, the first-line drug for type 2 diabetes mellitus (T2DM), has additional effects on improvements of nonalcoholic fatty liver disease (NAFLD); however, there are no treatments for both T2DM and NAFLD. Previous studies have shown hepatoprotective effects of a mixture of lemon balm and dandelion (LD) through its antioxidant and anti-steatosis properties. Thus, combination effects of metformin and LD were examined in a high-fat diet (HFD)-induced metabolic disease mouse model. The model received an oral administration of distilled water, monotherapies of metformin and LD, or a metformin combination with LD for 12 weeks. The HFD-induced weight gain and body fat deposition were reduced more by the combination than either monotherapy. Blood parameters for NAFLD (i.e., alanine aminotransferase and triglyceride), T2DM (i.e., glucose and insulin), and renal functions (i.e., blood urea nitrogen and creatinine) were reduced in the combination. The combination further enhanced hepatic antioxidant activities, and improved insulin resistance via the AMP-activated protein kinase and lipid metabolism pathways. Histopathological analyses revealed that the metformin combination ameliorated the hepatic hypertrophy/steatosis, pancreatic endocrine/exocrine alteration, fat tissue hypertrophy, and renal steatosis, more than either monotherapy. These results suggest that metformin combined with LD can be promising for preventing and treating metabolic diseases involving insulin resistance. Full article
(This article belongs to the Special Issue Antioxidant Defence in Type 2 Diabetes)
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13 pages, 6659 KiB  
Article
3-Hydroxybutyrate Ameliorates the Progression of Diabetic Nephropathy
by Jeeyoun Jung, Woo Yeong Park, Yun Jin Kim, Mikyung Kim, Misun Choe, Kyubok Jin, Ji Hae Seo and Eunyoung Ha
Antioxidants 2022, 11(2), 381; https://doi.org/10.3390/antiox11020381 - 14 Feb 2022
Cited by 9 | Viewed by 3969
Abstract
Studies report beneficial effects of 3-hydroxybutyrate (3-OHB) on the treatment of type 2 diabetes and obesity, but the effects of 3-OHB on diabetic nephropathy have not been elucidated. This study was designed to investigate the efficacy and mechanism of 3-OHB against progression of [...] Read more.
Studies report beneficial effects of 3-hydroxybutyrate (3-OHB) on the treatment of type 2 diabetes and obesity, but the effects of 3-OHB on diabetic nephropathy have not been elucidated. This study was designed to investigate the efficacy and mechanism of 3-OHB against progression of diabetic nephropathy (DN). Mice (db/db) were fed normal chow, high-fat, or ketogenic diets (KD) containing precursors of 3-OHB. Hyperglycemia was determined based on random glucose level (≥250 mg/dL). Fasting blood glucose and body weights were measured once a week. Twenty four-hour urine albumin to creatinine ratio was determined 5 weeks after the differential diet. Energy expenditure was measured 9 weeks after the differential diet. Body weights were significantly lower in the KD group than those in other groups, but no significant differences in fasting blood glucose levels among three groups were observed. Urine albumin to creatinine ratio and serum blood urea nitrogen (BUN) to creatinine ratio in the KD group were significantly lower than in other groups. Histologic and quantitative analysis of mesangial area suggested that KD delayed the progression of DN phenotype in db/db mice. Metabolic cage analysis also revealed that KD increased energy expenditure in db/db mice. In vitro studies with proximal tubular cells revealed that 3-OHB stimulated autophagic flux. 3-OHB increased LC3 I to LC3 II ratio, phosphorylation of AMPK, beclin, p62 degradation, and NRF2 expression. Moreover, we found that 3-OHB attenuated high glucose-induced reactive oxygen species (ROS) levels in proximal tubular cells. In vivo study also confirmed increased LC3 and decreased ROS levels in the kidney of KD mice. In summary, this study shows in both in vivo and in vitro models that 3-OHB delays the progression of DN by augmenting autophagy and inhibiting oxidative stress. Full article
(This article belongs to the Special Issue Antioxidant Defence in Type 2 Diabetes)
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Review

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22 pages, 7181 KiB  
Review
Selenium and Selenoproteins at the Intersection of Type 2 Diabetes and Thyroid Pathophysiology
by Francesca Gorini and Cristina Vassalle
Antioxidants 2022, 11(6), 1188; https://doi.org/10.3390/antiox11061188 - 16 Jun 2022
Cited by 14 | Viewed by 4890
Abstract
Type 2 diabetes (T2D) is considered one of the largest global public-health concerns, affecting approximately more than 400 million individuals worldwide. The pathogenesis of T2D is very complex and, among the modifiable risk factors, selenium (Se) has recently emerged as a determinant of [...] Read more.
Type 2 diabetes (T2D) is considered one of the largest global public-health concerns, affecting approximately more than 400 million individuals worldwide. The pathogenesis of T2D is very complex and, among the modifiable risk factors, selenium (Se) has recently emerged as a determinant of T2D pathogenesis and progression. Selenium is considered an essential element with antioxidant properties, and is incorporated into the selenoproteins involved in the antioxidant response. Furthermore, deiodinases, the enzymes responsible for homeostasis and for controlling the activity of thyroid hormones (THs), contain Se. Given the crucial action of oxidative stress in the onset of insulin resistance (IR) and T2D, and the close connection between THs and glucose metabolism, Se may be involved in these fundamental relationships; it may cover a dual role, both as a protective factor and as a risk factor of T2D, depending on its basal plasma concentration and the individual’s diet intake. In this review we discuss the current evidence (from experimental, observational and randomized clinical studies) on how Se is associated with the occurrence of T2D and its influence on the relationship between thyroid pathophysiology, IR and T2D. Full article
(This article belongs to the Special Issue Antioxidant Defence in Type 2 Diabetes)
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