REVIEW article
Front. Endocrinol.
Sec. Diabetes: Molecular Mechanisms
This article is part of the Research TopicMitochondrial Dynamics and Endothelial Dysfunction: Implications for Metabolic DisordersView all 6 articles
Mitochondrial Bioenergetics Dysfunction in T2DM: Linking Oxidative Stress to Insulin Resistance
Provisionally accepted
- 1Department of Endo-crinology, Peking University Shenzhen Hospital, Shenzhen, China
- 2Shenzhen University Medical School, Shenzhen, China
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Insulin resistance (IR) is a core pathological feature of type 2 diabetes mellitus (T2DM) and is closely associated with mitochondrial dysfunction in insulin-sensitive tissues, including skeletal muscle, liver, and adipose tissue. Mitochondrial abnormalities—such as impaired oxidative phosphorylation (OXPHOS), dysregulated tricarboxylic acid (TCA) cycle, excessive reactive oxygen species (ROS) production, and altered mitochondrial dynamics—can contribute to IR by oxidatively modifying insulin-signaling proteins and activating inflammatory pathways (JNK/NF-κB). Recent work also implicates microRNAs (miRNAs) as modulators that link mitochondrial function and redox balance to insulin action; however, their magnitude and tissue specificity in human T2DM remain to be defined. Therapeutic strategies that target mitochondrial bioenergetics and redox homeostasis show promise, while miRNA-directed approaches are emerging. This review provides an explanatory synthesis aimed at distinguishing associations within the mitochondria-ROS-insulin resistance axis supported by solid evidence from findings influenced by specific contexts, and outlines translational opportunities and their associated delivery bottlenecks.
Keywords: type 2 diabetes, Insulin Resistance, Mitochondria, Oxidative stress/ROS, electron transport chain, Reverse electron transport, tricarboxylic acid cycle, delivery
Received: 28 Jul 2025; Accepted: 27 Nov 2025.
Copyright: © 2025 Feng, Tan and Lu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Zhenlin Tan
Donghui Lu
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