Enhanced insulin signaling via circulating ATG7: A potential therapeutic strategy for diabetes
Abstract
Diabetes and insulin resistance (IR) remain major global health challenges, underscoring the need for novel therapeutic strategies. Here, we identify an autophagy-independent role of circulating autophagy-related gene 7 (ATG7) in metabolic regulation. Circulating ATG7 enhances insulin sensitivity and glucose homeostasis by directly interacting with IRS1 and modulating insulin signaling (IS) through liver–muscle crosstalk. Mechanistically, ATG7 binds to IRS1, promoting its activation and the propagation of downstream IS. Notably, we identify an ATG7-derived peptide (Aap2) that recapitulates ATG7’s insulin-sensitizing effects and improves glycemic control in both Type 1 and Type 2 diabetic mouse models. These findings establish ATG7 as a key regulator of IS and suggest that targeting ATG7 may represent a promising therapeutic approach for IR and diabetes.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (27)
Yi Guan
State Key Laboratory of Emerging Infectious Diseases, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong
Yang Yu
Mengdi Fu
Clinical Translational Research Center, Shengjing Hospital, Health Sciences Institute, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, Key Laboratory of Liaoning Province, Health Sciences Institute, China Medical University
Hongde Xu
Clinical Translational Research Center, Shengjing Hospital, Health Sciences Institute, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, Key Laboratory of Liaoning Province, Health Sciences Institute, China Medical University
Eunyoung Lee
Department of Medical Physiology, Graduate School of Medicine, Research Institute of Disaster Medicine, Chiba University
Hanfeng Wang
Clinical Translational Research Center, Shengjing Hospital, Health Sciences Institute, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, Key Laboratory of Liaoning Province, Health Sciences Institute, China Medical University
José María Moreno-Navarrete
Institut d’Investigació Biomèdica de Girona, University of Girona
Chengsi Deng
Clinical Translational Research Center, Shengjing Hospital, Health Sciences Institute, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, Key Laboratory of Liaoning Province, Health Sciences Institute, China Medical University
Yuheng Li
State Key Laboratory of Structural Chemistry
Kangjing Song
Clinical Translational Research Center, Shengjing Hospital, Health Sciences Institute, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, Key Laboratory of Liaoning Province, Health Sciences Institute, China Medical University
Qiqiang Guo
Clinical Translational Research Center, Shengjing Hospital, Health Sciences Institute, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, Key Laboratory of Liaoning Province, Health Sciences Institute, China Medical University
Xiaoyou Jiang
Clinical Translational Research Center, Shengjing Hospital, Health Sciences Institute, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, Key Laboratory of Liaoning Province, Health Sciences Institute, China Medical University
Xiaoyu Song
Department of Chemistry
Wendong Guo
Clinical Translational Research Center, Shengjing Hospital, Health Sciences Institute, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, Key Laboratory of Liaoning Province, Health Sciences Institute, China Medical University
Yanling Feng
Clinical Translational Research Center, Shengjing Hospital, Health Sciences Institute, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, Key Laboratory of Liaoning Province, Health Sciences Institute, China Medical University
Fei Yi
Clinical Translational Research Center, Shengjing Hospital, Health Sciences Institute, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, Key Laboratory of Liaoning Province, Health Sciences Institute, China Medical University
Ning Bai
Clinical Translational Research Center, Shengjing Hospital, Health Sciences Institute, Key Laboratory of Medical Cell Biology, Ministry of Education, College of Basic Medical Science, Key Laboratory of Liaoning Province, Health Sciences Institute, China Medical University
Jiabin Li
Key Laboratory of Medical Cell Biology, Ministry of Education, School of Life Sciences, China Medical University
Jingyang Chen
Medical Basic Experimental Teaching Centre, China Medical University
Wenjing Shen
Yunnan Open University, Kunming, China.
Wan Yu
Department of Gerontology and Geriatrics, Shengjing Hospital of China Medical University
Difei Wang
Siru Hou
Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University
Jichun Tan
Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University
José-Manuel Fernández-Real
Institut d’Investigació Biomèdica de Girona, University of Girona
Antonio Vidal-Puig
Centro de Investigacion Principe Felipe, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM)
Liu Cao
Computational Biology Department, School of Computer Science