Publication Name	World Journal of Diabetes
Manuscript ID	113938
Country	China

Category	Toxicology
Manuscript Type	Basic Study
Article Title	Study on the role of CCM3 in neurological damage in lead exposure of diabetes
Manuscript Source	Unsolicited Manuscript
All Author List	Xu Liang, Liu-Xue Yang, Tao Tao, Wen-Jia Ding, Xin-Yi Tang, Zhi-Bin Shang, Hang Zhou, Yun He and Yi Sun
Funding Agency and Grant Number	Funding Agency Grant Number National Natural Science Foundation of China 82060586 Natural Science Foundation of Guangxi Province 2023GXNSFAA026122， 2020GXNSFAA238036 National Guangxi College Students Innovation and Entrepreneurship Training Program S202410601154, S202410601162 and X202410601236 China Scholarship Council 202208455012
Corresponding Author	Yi Sun, Department of Toxicology, Guilin Medical University, No. 1 Zhiyuan Road, Lingui District, Guilin 541199, Guangxi Zhuang Autonomous Region, China. sunyide163@163.com
Key Words	CCM3; Lead; Diabetes; PI3K-AKT; Ferroptosis
Core Tip	Using a diabetic, CCM3-deficient mouse model with lead exposure, this study demonstrates that lead exposure, diabetes, and CCM3 loss synergistically increase blood glucose and lead levels, resulting in neural injury that precedes vascular damage. Lead triggers early neural impairment by inhibiting the PI3K-AKT signaling pathway and promoting ferroptosis, a mechanism distinct from glucose-related effects. Epidemiological analyses further confirm that interactions among urinary lead levels, blood glucose, and the CCM3 single-nucleoyide polymorphisms rs6784267 significantly influence the neurotransmitter metabolites vanillylmandelic acid and homovanillic acid, consistent with animal findings. Collectively, these results provide a scientific basis for the prevention early neural damage involving environmental, metabolic, and genetic factors.
Citation	Liang X, Yang LX, Tao T, Ding WJ, Tang XY, Shang ZB, Zhou H, He Y, Sun Y. Study on the role of CCM3 in neurological damage in lead exposure of diabetes. World J Diabetes 2026; In press

Received	2025-09-07 06:46
Peer-Review Started	2025-09-08 00:06
First Decision by Editorial Office Director	2025-10-22 08:49
Return for Revision	2025-10-22 08:49
Revised	2025-11-15 03:24
Publication Fee Transferred	2025-11-23 03:20
Second Decision by Editor	2026-05-28 02:37
Second Decision by Editor-in-Chief
Final Decision by Editorial Office Director	2026-05-28 03:15
Articles in Press	2026-05-28 03:15
Edit the Manuscript by Language Editor
Typeset the Manuscript

ISSN	1948-9358 (online)
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