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    Home > Active Ingredient News > Endocrine System > Cell Reports Jianyuan Zhao's team reveals a new pathological mechanism of homocysteine ​​modification in the development of diabetes

    Cell Reports Jianyuan Zhao's team reveals a new pathological mechanism of homocysteine ​​modification in the development of diabetes

    • Last Update: 2021-10-21
    • Source: Internet
    • Author: User
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    Editor | xi Homocysteine ​​(Hcy) is not involved in protein synthesis, but it is considered by Japanese scholars to be the most important indicator amino acid for human health
    .

    Hcy is a confirmed "independent risk factor for birth defects and cardiovascular and cerebrovascular diseases", and its importance in other disease fields is being increasingly recognized
    .

    In recent years, researchers have found that plasma Hcy levels are very closely related to diabetes.
    More than one-third of type 2 diabetes patients are accompanied by hyperhomocysteinemia, and diabetes patients with elevated plasma homocysteine The risk of death has increased significantly
    .

    Whether hyperhomocysteinemia is a cause or consequence of type 2 diabetes is unclear
    .

    On October 12, 2021, the research team of Jianyuan Zhao from the School of Life Sciences of Fudan University published an article Homocysteine ​​inhibits pro-insulin receptor cleavage and causes insulin resistance via protein cysteine-homocysteinylation in Cell Reports, explaining the secrets
    .

     Researchers have found that high levels of Hcy can be spontaneously modified to the cysteine ​​site of the insulin receptor precursor protein through disulfide bonds.
    This post-translational modification can disrupt the insulin receptor in the endoplasmic reticulum and Golgi apparatus.
    The maturation process ultimately leads to a significant reduction in the mature form of insulin receptor protein
    .

    The insulin receptor is located on the cell membrane and is responsible for receiving insulin stimulation and undertaking the initial task of insulin signal transmission.
    The decrease of its protein content makes the transmission of insulin signal directly inhibited in the first step, which leads to severe insulin resistance.

    .

     The team’s further research found that a protein called disulfide isomerase (PDI) located in the endoplasmic reticulum can efficiently remove the C-Hcy modification on the insulin receptor.
    This is the first time that this modification has been discovered.
    Modification enzyme
    .

    In addition, overexpression of PDI in a mouse model can effectively reverse the phenotype of insulin resistance induced by high Hcy, suggesting that C-Hcy modification in the endoplasmic reticulum may be an ideal target for intervention in Hcy-related insulin resistance.
    It provides guidance for the development of new programs for the prevention and treatment of type 2 diabetes
    .

     Zhang Xuan, a doctoral student at Fudan University, is the first author
    .

    Researcher Zhao Jianyuan, School of Life Sciences, Fudan University, is the corresponding author
    .

    This work is also the subsequent discovery by Jianyuan Zhao’s team and collaborators of the genetic causes of Hcy metabolism disorders (Circulation 2012, 2017; Cell Research 2013; European Heart Journal 2014), revealing that Hcy modifies protein lysine residues through amide bonds to induce DNA damage response disorders Another important discovery after oxidative stress (Cell Reports 2018; EMBO Molecular Medicine 2020) is expected to provide a new perspective for the prevention and intervention of Hcy-related diseases
    .

    Schematic diagram: High levels of Hcy can be modified to the insulin receptor precursor protein, disrupting its maturation process in the endoplasmic reticulum and Golgi apparatus, and ultimately leading to a significant decrease in the mature form of insulin receptor on the cell membrane
    .

     Original link: https://doi.
    org/10.
    1016/j.
    celrep.
    2021.
    109821 Platemaker: Notes for reprinting on the 11th [Non-original article] The copyright of this article belongs to the author of the article.
    Personal forwarding and sharing are welcome.
    Reprinting without permission is forbidden by the author.
    All statutory rights, offenders must be investigated
    .

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