Type 1 diabetes (T1DM) is a chronic autoimmune disease, with a strong genetic background, leading to a gradual loss of pancreatic beta-cells, which secrete insulin and control glucose homeostasis. Patients with T1DM require life-long substitution with insulin and are at high risk for development of severe secondary complications. The incidence of T1DM has been continuously growing in the last decades, indicating an important contribution of environmental factors. Accumulating data indicates that sphingolipids may be crucially involved in T1DM development. The serum lipidome of T1DM patients is characterized by significantly altered sphingolipid composition compared to nondiabetic, healthy probands. Recently, several polymorphisms in the genes encoding the enzymatic machinery for sphingolipid production have been identified in T1DM individuals. Evidence gained from studies in rodent islets and beta-cells exposed to cytokines indicates dysregulation of the sphingolipid biosynthetic pathway and impaired function of several sphingolipids. Moreover, a number of glycosphingolipids have been suggested to act as beta-cell autoantigens. Studies in animal models of autoimmune diabetes, such as the Non Obese Diabetic (NOD) mouse and the LEW.1AR1-iddm (IDDM) rat, indicate a crucial role of sphingolipids in immune cell trafficking, islet infiltration and diabetes development. In this review, the up-to-date status on the findings about sphingolipids in T1DM will be provided, the under-investigated research areas will be identified and perspectives for future studies will be given.

中文翻译：

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1型糖尿病的鞘脂：专注于β细胞。

1型糖尿病（T1DM）是一种慢性自身免疫性疾病，具有很强的遗传背景，会导致胰岛β细胞逐渐丢失，后者会分泌胰岛素并控制葡萄糖的体内稳态。患有T1DM的患者需要终生用胰岛素替代，并且有发生严重继发性并发症的高风险。在过去的几十年中，T1DM的发病率一直在持续增长，这表明环境因素的重要贡献。积累的数据表明鞘脂可能与T1DM的发展密切相关。与非糖尿病，健康先证者相比，T1DM患者的血清脂质组的特征是鞘脂成分明显改变。最近，在T1DM个体中已经发现了编码鞘氨醇生产酶机制的基因中的几种多态性。从啮齿动物的胰岛和暴露于细胞因子的β细胞的研究中获得的证据表明，鞘脂生物合成途径的调节异常和几种鞘脂的功能受损。此外，已经提出许多糖鞘脂可作为β细胞自身抗原。对自身免疫性糖尿病动物模型的研究，例如非肥胖糖尿病（NOD）小鼠和LEW.1AR1-iddm（IDDM）大鼠，表明鞘脂在免疫细胞运输，胰岛浸润和糖尿病发展中起着至关重要的作用。在这篇综述中，将提供有关T1DM中鞘脂的最新发现，鉴定未充分研究的领域以及未来研究的前景。