Pathophysiological significance of hepatokine overproduction in type 2 diabetes

被引：10

作者：

Misu H. ^{[1
,2
]}

机构：

[1] Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa, 920-8641, Ishikawa

[2] PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama

来源：

Diabetology International | 2018年 / 9卷 / 4期

基金：

日本学术振兴会; 日本科学技术振兴机构;

关键词：

Hepatokines; Insulin resistance; LECT2; Selenoprotein P;

D O I：

10.1007/s13340-018-0368-9

中图分类号：

学科分类号：

摘要：

Currently, many studies draw attention to novel secretory factors, such as adipokines or myokines, derived from the tissues that were not originally recognized as endocrine organs. The liver may contribute to the onset of various kinds of pathologies of type 2 diabetes by way of the production of secretory proteins “hepatokines.” Using the comprehensive gene expression analyses in human livers, we have rediscovered selenoprotein P and LECT2 as hepatokines involved in the onset of dysregulated glucose metabolism. Overproduction of selenoprotein P, previously reported as a transport protein of selenium, induces insulin resistance and hyperglycemia in type 2 diabetic condition. Selenoprotein P also contributes to vascular complications of type 2 diabetes directly by inducing VEGF resistance in vascular endothelial cells. Notably, selenoprotein P impairs health-promoting effects of exercise by inhibiting ROS/AMPK/PGC-1α pathway in the skeletal muscle through its receptor LRP1. Overproduction of LECT2, previously reported as a neutrophil chemotactic protein, links obesity to insulin resistance in the skeletal muscle. Further studies would develop novel diagnostic or therapeutic procedures targeting hepatokines to combat over-nutrition-related diseases such as type 2 diabetes. © 2018, The Japan Diabetes Society.

引用

页码：224 / 233

页数：9

共 51 条

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