title: The emerging role of redox-sensitive Nrf2-Keap1 pathway in diabetes.
abstract: The pathogenic processes involving in the development of diabetes range from autoimmune destruction of pancreatic β-cells with consequent insulin deficiency to abnormalities that result in resistance to insulin action. The major contributing factor for excessive β-cell death includes oxidative stress-mediated mitochondrial damage, which creates an imbalance in redox homeostasis. Yet, β-cells have evolved adaptive mechanisms to endure a wide range of stress conditions to safeguard its potential functions. These include 'Nrf2/Keap1' pathway, a key cellular defense mechanism, to combat oxidative stress by regulating phase II detoxifying and antioxidant genes. During diabetes, redox imbalance provokes defective Nrf2-dependent signaling and compromise antioxidant capacity of the pancreas which turnout β-cells to become highly vulnerable against various insults. Hence, identification of small molecule activators of Nrf2/Keap1 pathway remains significant to enhance cellular defense to overcome the burden of oxidative stress related disturbances. This review summarizes the molecular mechanism behind Nrf2 activation and the impact of Nrf2 activators in diabetes and its complications.
authors.affiliation: Department of Biotechnology, SRM University, Kattankulathur 603 203, Tamilnadu, India.
authors.forename: Elango
authors.initials: E
authors.lastname: Bhakkiyalakshmi
authors.affiliation: SRM Research Institute, SRM University, Kattankulathur 603 203, Tamilnadu, India.
authors.forename: Dornadula
authors.initials: D
authors.lastname: Sireesh
authors.affiliation: Department of Biotechnology, Anna University-BIT Campus, Tiruchirappalli 620 024, Tamilnadu, India.
authors.forename: Palanisamy
authors.initials: P
authors.lastname: Rajaguru
authors.affiliation: Department of Radiology, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
authors.forename: Ramasamy
authors.initials: R
authors.lastname: Paulmurugan
authors.affiliation: SRM Research Institute, SRM University, Kattankulathur 603 203, Tamilnadu, India. Electronic address: ramkumar.km@res.srmuniv.ac.in.
authors.forename: Kunka Mohanram
authors.initials: KM
authors.lastname: Ramkumar
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D010084:Oxidation-Reduction; D015398:Signal Transduction; D013312:Stress, Physiological
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human
keywords: Antioxidants; Bardoxolone methyl (PubChem CID: 400769); Cinnamaldehyde (PubChem CID: 637511); Curcumin (PubChem CID: 969516); Diabetes; Epigallocatechin gallate (PubChem CID: 65064); MG-132 (PubChem CID: 462382); Magnesium Lithospermate B (PubChem CID: 6438135); Nrf2 activators; Nrf2–Keap1 pathway; Oxidative stress; Pterostilbene (PubChem CID: 5281727); Resveratrol (PubChem CID: 445154); Sulforaphane (PubChem CID: 5350); tert-Butylhydroquinone (PubChem CID: 16043)