Xiaorui Yu, Jiawang Tao, Yuhang Wu, Yan Chen, Penghui Li, Fan Yang, Miaoxiu Tang, Abdul Sammad, Yu Tao, Yingying Xu, Yin-Xiong Li
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引用次数: 0
Abstract
Backgruound: Insulin resistance (IR) is the key pathological basis of many metabolic disorders. Lack of asialoglycoprotein receptor 1 (ASGR1) decreased the serum lipid levels and reduced the risk of coronary artery disease. However, whether ASGR1 also participates in the regulatory network of insulin sensitivity and glucose metabolism remains unknown.
Methods: The constructed ASGR1 knockout mice and ASGR1-/- HepG2 cell lines were used to establish the animal model of metabolic syndrome and the IR cell model by high-fat diet (HFD) or drug induction, respectively. Then we evaluated the glucose metabolism and insulin signaling in vivo and in vitro.
Results: ASGR1 deficiency ameliorated systemic IR in mice fed with HFD, evidenced by improved insulin intolerance, serum insulin, and homeostasis model assessment of IR index, mainly contributed from increased insulin signaling in the liver, but not in muscle or adipose tissues. Meanwhile, the insulin signal transduction was significantly enhanced in ASGR1-/- HepG2 cells. By transcriptome analyses and comparison, those differentially expressed genes between ASGR1 null and wild type were enriched in the insulin signal pathway, particularly in phosphoinositide 3-kinase-AKT signaling. Notably, ASGR1 deficiency significantly reduced hepatic gluconeogenesis and glycogenolysis.
Conclusion: The ASGR1 deficiency was consequentially linked with improved hepatic insulin sensitivity under metabolic stress, hepatic IR was the core factor of systemic IR, and overcoming hepatic IR significantly relieved the systemic IR. It suggests that ASGR1 is a potential intervention target for improving systemic IR in metabolic disorders.
期刊介绍:
The aims of the Diabetes & Metabolism Journal are to contribute to the cure of and education about diabetes mellitus, and the advancement of diabetology through the sharing of scientific information on the latest developments in diabetology among members of the Korean Diabetes Association and other international societies.
The Journal publishes articles on basic and clinical studies, focusing on areas such as metabolism, epidemiology, pathogenesis, complications, and treatments relevant to diabetes mellitus. It also publishes articles covering obesity and cardiovascular disease. Articles on translational research and timely issues including ubiquitous care or new technology in the management of diabetes and metabolic disorders are welcome. In addition, genome research, meta-analysis, and randomized controlled studies are welcome for publication.
The editorial board invites articles from international research or clinical study groups. Publication is determined by the editors and peer reviewers, who are experts in their specific fields of diabetology.