Glucose-sensitive Myokine/Cardiokine MG53 Regulates Systemic Insulin Response and Metabolic Homeostasis

Abstract:

Mitsugumin 53 (MG53 or TRIM72), a striated muscle-enriched E3 ligase, plays an essential role in metabolic syndrome and type 2 diabetes (T2D). However, it is unknown how MG53 from muscle regulates systemic insulin response and metabolic homeostasis. Here, we demonstrate that MG53 is a metabolism-regulated myokine/cardiokine that governs the inter-organ regulation of insulin sensitivity. High glucose or insulin induces MG53 secretion from striated muscle, and hyperglycemia is accompanied by increased circulating MG53 in diabetic humans and rodents. Elevating blood MG53 causes systemic insulin resistance and metabolic syndrome in mice, whereas neutralizing circulating MG53 with a monoclonal antibody has therapeutic effects in T2D db/db mice. Mechanistically, MG53 binds to the extracellular domain of the insulin receptor and blocks receptor signaling. Thus, MG53 has dual action as a myokine/cardiokine and an E3 ligase, synergistically inhibiting the insulin signaling pathway. Targeting circulating MG53 opens a new therapeutic avenue for T2D and its complications.

肖瑞平，国家杰出青年基金获得者、北京大学终身讲席教授。现任北京大学分子医学研究所所长。

1979年至1987年，肖瑞平就读于在同济医科大学，获医学学士和硕士，1995年获得马里兰大学生理学博士。1996年获聘NIH研究员，2003年成为NIH终身资深研究员。2010年3月辞去美国职位，全时在北京大学工作。她长期从事心血管及代谢疾病的基础和转化研究，在国际一流学术刊物发表文章100余篇，引用11000余次。

2000年至今为美国心脏学会中大西洋地区指导委员会委员，2002年至今担任国际心脏学会(ISHR)理事，2004入选美国临床医学研究会会士(American Society for Clinical Investigation, ASCI)。担任包括《新英格兰医学杂志》副主编在内的多个国际权威杂志副主编/编委。

11月23日（周四）15:00-16:00

清华大学医学楼B323