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      Ferroptosis as a potential new therapeutic target for diabetes and its complications

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          Abstract

          Diabetes is a complex metabolic disease. In recent years, diabetes and its chronic complications have become a health hotspot of global concern. It is very important to find promising therapeutic targets and directions. Ferroptosis is a new type of programmed cell death that is different from cell necrosis, apoptosis, and autophagy. Ferroptosis is mainly characterized by iron-dependent lipid peroxidation. With the reduction of the anti-oxidative capacity of cells, the accumulated reactive lipid oxygen species will cause oxidative cell death and lead to ferroptosis at lethal levels. Recent studies have shown that ferroptosis plays an important regulatory role in the initiation and development of diabetes, as well as various complications of diabetes. In this review, we will summarize new findings related to ferroptosis and diabetic complications and propose ferroptosis as a potential target for treating diabetic complications.

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          Most cited references119

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          Ferroptosis: an iron-dependent form of nonapoptotic cell death.

          Nonapoptotic forms of cell death may facilitate the selective elimination of some tumor cells or be activated in specific pathological states. The oncogenic RAS-selective lethal small molecule erastin triggers a unique iron-dependent form of nonapoptotic cell death that we term ferroptosis. Ferroptosis is dependent upon intracellular iron, but not other metals, and is morphologically, biochemically, and genetically distinct from apoptosis, necrosis, and autophagy. We identify the small molecule ferrostatin-1 as a potent inhibitor of ferroptosis in cancer cells and glutamate-induced cell death in organotypic rat brain slices, suggesting similarities between these two processes. Indeed, erastin, like glutamate, inhibits cystine uptake by the cystine/glutamate antiporter (system x(c)(-)), creating a void in the antioxidant defenses of the cell and ultimately leading to iron-dependent, oxidative death. Thus, activation of ferroptosis results in the nonapoptotic destruction of certain cancer cells, whereas inhibition of this process may protect organisms from neurodegeneration. Copyright © 2012 Elsevier Inc. All rights reserved.
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            Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease

            Ferroptosis is a form of regulated cell death characterized by the iron-dependent accumulation of lipid hydroperoxides to lethal levels. Emerging evidence suggests that ferroptosis represents an ancient vulnerability caused by the incorporation of polyunsaturated fatty acids into cellular membranes, and cells have developed complex systems that exploit and defend against this vulnerability in different contexts. The sensitivity to ferroptosis is tightly linked to numerous biological processes, including amino acid, iron, and polyunsaturated fatty acid metabolism, and the biosynthesis of glutathione, phospholipids, NADPH, and coenzyme Q10. Ferroptosis has been implicated in the pathological cell death associated with degenerative diseases (i.e., Alzheimer's, Huntington's, and Parkinson's diseases), carcinogenesis, stroke, intracerebral hemorrhage, traumatic brain injury, ischemia-reperfusion injury, and kidney degeneration in mammals and is also implicated in heat stress in plants. Ferroptosis may also have a tumor-suppressor function that could be harnessed for cancer therapy. This Primer reviews the mechanisms underlying ferroptosis, highlights connections to other areas of biology and medicine, and recommends tools and guidelines for studying this emerging form of regulated cell death.
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              Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

              Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium-glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes.
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                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                19 January 2023
                19 January 2023
                01 March 2023
                : 12
                : 3
                : e220419
                Affiliations
                [1 ]Graduate College of Anhui University of Chinese Medicine , Hefei, China
                [2 ]Department of Endocrinology , The Second Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China
                [3 ]College of Acupuncture-moxibustion and Tuina , Anhui University of Chinese Medicine, Hefei, China
                [4 ]Department of Geriatrics , Zhongshan Hospital, Fudan University, Shanghai, China
                Author notes
                Correspondence should be addressed to X Ge or Q Zhang or T Cheng: xiage@ 123456ahtcm.edu.cn or zqp202202@ 123456163.com or chengtong.ct@ 123456163.com

                *(Q Deng and Y Zhu contributed equally to this work)

                Author information
                http://orcid.org/0000-0002-8630-718X
                Article
                EC-22-0419
                10.1530/EC-22-0419
                9986392
                36656308
                2d5f0425-56dd-4605-8907-70840ecaca1a
                © the author(s)

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 04 January 2023
                : 19 January 2023
                Categories
                Review

                ferroptosis,diabetes,diabetic complications
                ferroptosis, diabetes, diabetic complications

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