Gao M, Dai MT, Gong GH. Dysfunctional glucose metabolism triggers oxidative stress to induce kidney injury in diabetes. World J Diabetes 2025; 16(4): 102554 [DOI: 10.4239/wjd.v16.i4.102554]
Corresponding Author of This Article
Guo-Hua Gong, PhD, Professor, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Chashan Higher Education Park, Wenzhou 325035, Zhejiang Province, China. guohgong@wmu.edu.cn
Research Domain of This Article
Medicine, Research & Experimental
Article-Type of This Article
Editorial
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Diabetes. Apr 15, 2025; 16(4): 102554 Published online Apr 15, 2025. doi: 10.4239/wjd.v16.i4.102554
Dysfunctional glucose metabolism triggers oxidative stress to induce kidney injury in diabetes
Meng Gao, Meng-Ting Dai, Guo-Hua Gong
Meng Gao, Meng-Ting Dai, Guo-Hua Gong, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
Meng Gao, Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
Author contributions: Gao M and Dai MT contributed to the discussion of the literature and design of the manuscript; Gao M and Gong GH contributed to the writing and editing of the manuscript; Gong GH designed the overall concept and outline of the manuscript; All authors read and approved the final version of the manuscript to be published.
Supported by The Basic Research Project of Wenzhou Municipal Science and Technology Bureau, No. Y20240008; The Medical Health Science and Technology Project of Zhejiang Provincial Health Commission, No. 2024KY138; and The Key Laboratory of School of Laboratory Medicine and Life Sciences, Wenzhou Medical University of China, No. JS2023003.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Guo-Hua Gong, PhD, Professor, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Chashan Higher Education Park, Wenzhou 325035, Zhejiang Province, China. guohgong@wmu.edu.cn
Received: October 22, 2024 Revised: January 14, 2025 Accepted: February 5, 2025 Published online: April 15, 2025 Processing time: 129 Days and 23.1 Hours
Abstract
In this editorial, we discussed the article published in the recent issue of the World Journal of Diabetes. To understand the effect of mizagliflozin on kidney injury induced by diabetes, we focused on the mechanisms by which high glucose triggers oxidative stress and contributes to kidney injury in diabetes. The high level of unmetabolized glucose reaching the kidney triggers glucose reabsorption by renal tubules, which elevates the cellular glucose level of renal cells. High glucose induces lactate dehydrogenase overexpression and thus shifts glucose metabolism, which causes mitochondrial dysfunction. Mitochondria generate approximately 90% of the reactive oxygen species in cells, whose dysfunction further alters glucose metabolism and enhances reactive oxygen species generation. Oxidative stress stimulates proinflammatory factor production and kidney inflammatory injury. Mizagliflozin decreases glucose reabsorption and thus ameliorates diabetes-induced kidney injury.
Core Tip: In diabetes, insulin resistance and insufficient insulin release lead to a decrease in glucose uptake by muscles and fat tissues, resulting in elevated blood glucose levels, which are dangerous to human organs. The tolerance of high glucose switches the metabolism of glucose, which causes mitochondrial dysfunction. Oxidative stress induced by excess reactive oxygen species generated by dysfunctional mitochondria causes cell damage and thus stimulates proinflammatory factor production and tissue injury. Therefore, antidiabetic therapies are aimed at decreasing blood glucose and oxidative stress.
