Počet záznamů: 1  

Redox Homeostasis in Pancreatic beta-Cells: From Development to Failure

  1. 1.
    0542431 - FGÚ 2022 RIV CH eng J - Článek v odborném periodiku
    Benáková, Štěpánka - Holendová, Blanka - Plecitá-Hlavatá, Lydie
    Redox Homeostasis in Pancreatic beta-Cells: From Development to Failure.
    Antioxidants. Roč. 10, č. 4 (2021), č. článku 526. E-ISSN 2076-3921
    Grant CEP: GA ČR(CZ) GA20-00408S
    Institucionální podpora: RVO:67985823
    Klíčová slova: redox signaling * oxidative stress * redox homeostasis * pancreatic beta-cells * de/differentiation * inflammation
    Obor OECD: Endocrinology and metabolism (including diabetes, hormones)
    Impakt faktor: 7.675, rok: 2021
    Způsob publikování: Open access
    https://www.mdpi.com/2076-3921/10/4/526

    Redox status is a key determinant in the fate of beta-cell. These cells are not primarily detoxifying and thus do not possess extensive antioxidant defense machinery. However, they show a wide range of redox regulating proteins, such as peroxiredoxins, thioredoxins or thioredoxin reductases, etc., being functionally compartmentalized within the cells. They keep fragile redox homeostasis and serve as messengers and amplifiers of redox signaling. beta-cells require proper redox signaling already in cell ontogenesis during the development of mature beta-cells from their progenitors. We bring details about redox-regulated signaling pathways and transcription factors being essential for proper differentiation and maturation of functional beta-cells and their proliferation and insulin expression/maturation. We briefly highlight the targets of redox signaling in the insulin secretory pathway and focus more on possible targets of extracellular redox signaling through secreted thioredoxin1 and thioredoxin reductase1. Tuned redox homeostasis can switch upon chronic pathological insults towards the dysfunction of beta-cells and to glucose intolerance. These are characteristics of type 2 diabetes, which is often linked to chronic nutritional overload being nowadays a pandemic feature of lifestyle. Overcharged beta-cell metabolism causes pressure on proteostasis in the endoplasmic reticulum, mainly due to increased demand on insulin synthesis, which establishes unfolded protein response and insulin misfolding along with excessive hydrogen peroxide production. This together with redox dysbalance in cytoplasm and mitochondria due to enhanced nutritional pressure impact beta-cell redox homeostasis and establish prooxidative metabolism. This can further affect beta-cell communication in pancreatic islets through gap junctions. In parallel, peripheral tissues losing insulin sensitivity and overall impairment of glucose tolerance and gut microbiota establish local proinflammatory signaling and later systemic metainflammation, i.e., low chronic inflammation prooxidative properties, which target beta-cells leading to their dedifferentiation, dysfunction and eventually cell death.
    Trvalý link: http://hdl.handle.net/11104/0319840

     
     
Počet záznamů: 1  

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