Selenoprotein S: a therapeutic target for diabetes and macroangiopathy?

Abstract

Inflammatory response, oxidative stress, and endoplasmic reticulum (ER) stress are important pathophysiological bases of the occurrence and development of diabetes mellitus (DM) and macroangiopathy complications. Selenoprotein S (SELENOS) is involved in the regulation of these mechanisms; therefore, its association with DM and macroangiopathy has gradually received attention from scholars worldwide. SELENOS has different biological functions in different tissues and organs: it exerts antioxidant protection and has anti-ER stress effects in the pancreas and blood vessels, while it promotes the occurrence and development of insulin resistance in the liver, adipose tissue, and skeletal muscle. In addition, studies have confirmed that some SELENOS gene polymorphisms can influence the inflammatory response and are closely associated with the risk for developing DM and macroangiopathy. Therefore, comprehensive understanding of the association between SELENOS and inflammation, oxidative stress, and ER stress may better elucidate and supplement the pathogenic mechanisms of DM and macroangiopathy complications. Furthermore, in-depth investigation of the association of SELENOS function in different tissues and organs with DM and macroangiopathy may facilitate the development of new strategies for the prevention and treatment of DM and macrovascular complications. Here, we summarize the consensus and controversy regarding functions of SELENOS on currently available evidence.

Serum selenoprotein P, but not selenium, predicts future hyperglycemia in a general Japanese population

“…Selenoproteins other than SELENOP, such as glutathione peroxidase 1 (GPX1) and selenoprotein S, are known to play a major role in regulation of glucose metabolism 33 , 34 . For example, overexpression of GPX1 was reported to exhibit insulin resistance and obesity in mice 35 .…”

High glucose and TGF-β1 reduce expression of endoplasmic reticulum-resident selenoprotein S and selenoprotein N in human mesangial cells

“…SELENOS also has different biological functions in different tissues and organs, even has opposite effects. In the pancreas and blood vessels, SELENOS can exert antioxidant protection and has anti-ER stress effects, while it promotes the occurrence and development of insulin resistance in the liver, adipose tissue, and skeletal muscle [22]. Even in the same tissue, Yao et al.’s study showed that relative distribution of ER-resident selenoprotein gene mRNA amounts and their responses to dietary Se deficiency were different in different skeletal muscle [23].…”

Research advance on the important role of selenoproteinin human health

“…ID 家族是一类包含折叠二聚硫氧还蛋白的硒蛋白，能够催化碘甲状腺氨酸 还原性脱碘 [17] 。主要分为三种类型：Ⅰ型脱碘酶(DIO1)、Ⅱ型脱碘酶 (DIO2)和Ⅲ型脱碘酶(DIO3)，其中 DIO1 主要存在于肝脏、肾脏和甲状腺 中，DIO2 存在于垂体、甲状腺、骨骼肌中，DIO3 主要存在于大脑皮层和皮肤 中 [18] 。三者高度保守的活性位点均含有 Sec，对维持酶活性至关重要 [19] 。 甲状腺激素(thyroid hormone，TH)是细胞生物学过程的重要调节剂，参与 22] ，Sel15、SelK、SelF、SelM、SelN 和 SelT 等均参与内质网氧化还原调节、 蛋白质折叠和细胞钙稳态等生理过程，SelH、SelV、SelW、SelO 分别在细胞核、 生殖细胞、骨骼肌、线粒体中发挥抗氧化作用，SelI 还参与生物膜磷脂的合成 氧化应激增加 [24] 。在不同肿瘤类型中 GPX3 具有双重作用，一项研究报道 GPX3…”