Institute of Medical Biochemistry and Molecular Biology, Rostock University Medical Center, University of Rostock, Schillingallee 70, D-18057, Rostock, Germany,
Diabetologia. 2014 May;57(5):856-9. doi: 10.1007/s00125-014-3206-z. Epub 2014 Mar 6.
The accurate quantification of beta cell mass in humans is one of the key challenges in understanding the role of beta cell loss and dysfunction in the pathogenesis of diabetes mellitus. Autopsy studies indicate that beta cell loss is not only a hallmark of autoimmune diabetes but also plays a pivotal role in type 2 diabetes, owing to the toxic effects of lipids, glucose and cytokines. Thus, there is an urgent need for non-invasive clinical techniques for beta cell mass quantification, which should be optimally integrated into standard diagnostic equipment in hospitals. In this issue of Diabetologia (Brom et al DOI 10.1007/s00125-014-3166-3) it is reported that single photon emission computed tomography (SPECT) data with (111)indium-labelled glucagon-like peptide-1 (GLP-1) receptor agonist exendin-3 correlate with the morphometric analysis of beta cell mass in a rat model of alloxan-induced diabetes. With this validation, the authors were able to demonstrate a significant loss of beta cell mass in C-peptide-negative type 1 diabetic patients. Thus, (111)indium-labelled exendin-3 could serve as a model tracer for future studies of larger cohorts of diabetic patients to monitor the dynamics of beta cell loss and regeneration. Despite the recent progress from SPECT imaging data there remain open questions that await clarification in the near future such as variations in GLP-1 receptor density and physiological variation of beta cell mass in relation to beta cell function. The use of GLP-1-based tracer analysis may open new clinical avenues for non-invasive quantification of beta cell mass in patients with newly diagnosed type 1 diabetes and prediabetic individuals with high titres of autoantibodies.
准确量化人类胰岛β细胞量是理解β细胞丢失和功能障碍在糖尿病发病机制中作用的关键挑战之一。尸检研究表明，β细胞丢失不仅是自身免疫性糖尿病的标志，而且在 2 型糖尿病中也起着关键作用，这是由于脂质、葡萄糖和细胞因子的毒性作用。因此，迫切需要用于β细胞量定量的非侵入性临床技术，这些技术应最佳整合到医院的标准诊断设备中。在本期《糖尿病学》（Brom 等人，DOI:10.1007/s00125-014-3166-3）中，据报道，（111）铟标记的胰高血糖素样肽-1（GLP-1）受体激动剂 exendin-3 的单光子发射计算机断层扫描（SPECT）数据与胰岛β细胞量的形态计量分析相关在链脲佐菌素诱导的糖尿病大鼠模型中。通过这种验证，作者能够证明 C 肽阴性 1 型糖尿病患者β细胞量的显著丢失。因此，（111）铟标记的 exendin-3 可作为未来对更大糖尿病患者队列进行研究的模型示踪剂，以监测β细胞丢失和再生的动态。尽管 SPECT 成像数据最近取得了进展，但仍有一些悬而未决的问题有待在不久的将来澄清，例如 GLP-1 受体密度的变化以及与β细胞功能相关的β细胞量的生理变化。基于 GLP-1 的示踪剂分析的使用可能为新诊断的 1 型糖尿病患者和自身抗体滴度高的糖尿病前期个体的β细胞量的非侵入性定量提供新的临床途径。
