Kulkarni Abhishek, Anderson Cara M, Mirmira Raghavendra G, Tersey Sarah A
Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
Metabolites. 2022 Apr 12;12(4):344. doi: 10.3390/metabo12040344.
The polyamines-putrescine, spermidine, and spermine-are polycationic, low molecular weight amines with cellular functions primarily related to mRNA translation and cell proliferation. Polyamines partly exert their effects via the hypusine pathway, wherein the polyamine spermidine provides the aminobutyl moiety to allow posttranslational modification of the translation factor eIF5A with the rare amino acid hypusine (droxy trescine ly). The "hypusinated" eIF5A (eIF5A) is considered to be the active form of the translation factor necessary for the translation of mRNAs associated with stress and inflammation. Recently, it has been demonstrated that activity of the polyamines-hypusine circuit in insulin-producing islet β cells contributes to diabetes pathogenesis under conditions of inflammation. Elevated levels of polyamines are reported in both exocrine and endocrine cells of the pancreas, which may contribute to endoplasmic reticulum stress, oxidative stress, inflammatory response, and autophagy. In this review, we have summarized the existing research on polyamine-hypusine metabolism in the context of β-cell function and diabetes pathogenesis.
多胺（腐胺、亚精胺和精胺）是具有多阳离子特性的低分子量胺类，其细胞功能主要与mRNA翻译和细胞增殖相关。多胺部分通过hypusine途径发挥作用，其中多胺亚精胺提供氨丁基部分，使翻译因子eIF5A通过罕见氨基酸hypusine（羟基丁赖氨酸）进行翻译后修饰。“hypusinated”的eIF5A（eIF5Ahyp）被认为是与应激和炎症相关的mRNA翻译所必需的翻译因子的活性形式。最近有研究表明，在炎症条件下，胰岛素生成胰岛β细胞中的多胺-hypusine回路活性促成了糖尿病发病机制。据报道，胰腺外分泌和内分泌细胞中的多胺水平均升高，这可能导致内质网应激、氧化应激、炎症反应和自噬。在本综述中，我们总结了在β细胞功能和糖尿病发病机制背景下关于多胺-hypusine代谢的现有研究。
