Researchers from the Peking University Institute of Molecular Medicine, the Ministry of Medicine and the Third Hospital recently confirmed in a new study: E3 ubiquitin ligase MG53 plays an important role in insulin resistance and metabolic diseases in insulin resistance and metabolic disorders "was published in the" Nature "magazine on January 27.
Professor Rui-Ping Xiao and Associate Researcher Chun-Mei Cao of the Institute of Molecular Medicine at Peking University are co-corresponding authors of this paper.
Metabolic syndrome (MS) is a pathological state in which a variety of metabolic components are abnormally aggregated. It is a complex group of metabolic disorder syndromes, including central obesity, type II diabetes or impaired glucose tolerance, hyperinsulinemia, and blood lipid disorders. , Hypertension, hyperuricemia, hyperviscosity, hypercoagulability, fatty liver and premature arteriosclerosis. In recent years, the incidence of metabolic syndrome has been increasing, which has seriously threatened human health.
Insulin resistance is the basic pathogenic factor of metabolic syndrome. Since skeletal muscle is responsible for 70-90% insulin-mediated glucose metabolism, insulin resistance in skeletal muscle may play a key role in the pathogenesis of metabolic syndrome and the resulting type 2 diabetes. Past studies have confirmed that skeletal muscle insulin resistance occurs early in the onset of metabolic syndrome and type 2 diabetes. However, the mechanism of insulin resistance in skeletal muscle is still poorly understood.
MG53 (mitsugumin 53) is a TRIM family protein discovered in recent years, which is specifically expressed in skeletal muscle and myocardium. In past studies, Professor Xiao Ruiping's group and other international research groups have confirmed that MG53 plays an important role in cell membrane repair and myocardial ischemic preconditioning. This protein has three specific motif structures that can be combined with proteins that are no longer needed by the cell, and these proteins are labeled with ubiquitin for degradation.
In this new article, the researchers confirmed in mice that skeletal muscle-specific MG53 mediates the degradation of insulin receptor and insulin receptor substrate (IRS1). When MG53 is upregulated, it can cause a metabolic syndrome characterized by insulin resistance, obesity, hypertension and disorders of lipid metabolism. The researchers found that MG53 expression was significantly increased in the insulin resistance model. Subsequently, they confirmed that overexpression of MG53 is sufficient to trigger muscle insulin resistance and metabolic syndrome. Conversely, by eliminating MG53 and maintaining the integrity of the insulin receptor, IRS1, and insulin signaling, diet-induced metabolic syndrome can be prevented. Mechanism research shows that MG53 targets the insulin receptor and IRS1 through the action of E3 ubiquitin ligase, and mediates their ubiquitin-dependent degradation, thereby regulating insulin signaling and metabolism in skeletal muscle.
New research results confirm that MG53 is an important negative regulator of insulin signaling in skeletal muscle, and MG53-mediated inhibition of skeletal muscle insulin signaling plays a key role in systemic insulin resistance and metabolic syndrome. This research provides us with a potential target for the treatment of various metabolic diseases and related cardiovascular diseases. (Bioon.com)
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