Mechanisms of skeletal muscle atrophy in type 2 diabetes mellitus

作者：Jingyi Yang, Yingdong Wang, Yuzhen Xu, X. Jia, Fangping Lu · 发表于：Frontiers in Physiology · 年份：2025 · DOI：10.3389/fphys.2025.1607873 · 被引用次数：10 · 研究领域：Medicine

Introduction ERS-induced apoptosis may play a pivotal role in diabetic skeletal muscle atrophy. However, the specific mechanisms by which ERS regulates skeletal muscle atrophy in diabetes remain unclear. The research examines the impact of endoplasmic reticulum stress (ERS) on skeletal muscle atrophy in type 2 diabetes mellitus (T2DM) mice. Methods Leptin receptor-deficient Db/db mice (n = 7, 24-week-old, male) were employed as a type 2 diabetes model, while age-matched male C57BL/6J mice (n = 7) served as normal controls. Pathway enrichment analysis of differentially expressed genes was performed based on transcriptome sequencing data, focusing on apoptosis, ERS, and ubiquitin-proteasome pathways. Skeletal muscle morphology was assessed via anatomical observation, Laminin Staining, and immunoblotting analysis (WB). WB was used to detect ERS markers (ATF6, p-eIF2α, Bip, p-JNK, Chop), apoptosis-related proteins (Bcl2, Bax, Cleaved Caspase-3, CytC), p-Akt, and muscle atrophy marker Atrogin1. Results Transcriptomic enrichment analysis confirmed specific activation of apoptosis, ERS, and ubiquitin-proteasome pathways. WB revealed upregulated ERS-related proteins, increased apoptotic proteins, decreased p-Akt expression, elevated Atrogin1 levels, and enhanced proteolytic activity. Db/db mice exhibited significant skeletal muscle atrophy, with Laminin Staining demonstrating reduced cross-sectional area (CSA) of muscle fibers. Discussion These findings uncovers a dual regulatory mec...