Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, 40225, Düsseldorf, Germany.
Institute of Biological Information Processing (Structural Biochemistry: IBI-7), Forschungszentrum Jülich GmbH, Wilhelm-Johnen-Straße, 52428, Jülich, Germany.
Sci Rep. 2024 Aug 22;14(1):19556. doi: 10.1038/s41598-024-70255-3.
Islet amyloid polypeptide (IAPP) is co-secreted with insulin from pancreatic ß-cells. Its oligomerisation is regarded as disease driving force in type 2 diabetes (T2D) pathology. Up to now, IAPP oligomers have been detected in affected tissues. IAPP oligomer concentrations in blood have not been analysed so far. Using the IAPP single-oligomer-sensitive and monomer-insensitive surface-based fluorescence intensity distribution analysis (sFIDA) technology, levels of IAPP oligomers in blood plasma from healthy controls and people with T2D in different disease stages where determined. Subsequently, the level of IAPP oligomerisation was introduced as the ratio between the IAPP oligomers determined with sFIDA and the total IAPP concentration determined with ELISA. Highest oligomerisation levels were detected in plasma of people with T2D without late complication and without insulin therapy. Their levels stand out significantly from the control group. Healthy controls presented with the lowest oligomerisation levels in plasma. In people with T2D without complications, IAPP oligomerisation levels correlated with disease duration. The results clearly demonstrate that IAPP oligomerisation in insulin-naïve patients correlates with duration of T2D. Although a correlation per se does not identify, which is cause and what is consequence, this result supports the hypothesis that IAPP aggregation is the driving factor of T2D development and progression. The alternative and conventional hypothesis explains development of T2D with increasing insulin resistance causing exhaustion of pancreatic ß-cells due to over-secretion of insulin, and thus IAPP, too, resulting in subsequent IAPP aggregation and fibril deposition in the pancreas. Further experiments and comparative analyses with primary tissues are warranted.
胰岛淀粉样多肽 (IAPP) 与胰腺β细胞分泌的胰岛素一起被分泌。其寡聚化被认为是 2 型糖尿病 (T2D) 病理中的致病因素。到目前为止，已经在受影响的组织中检测到 IAPP 寡聚体。迄今为止，尚未分析血液中的 IAPP 寡聚体浓度。使用 IAPP 单体敏感和单体不敏感的基于表面的荧光强度分布分析 (sFIDA) 技术，测定了健康对照组和不同疾病阶段的 T2D 患者的血浆中 IAPP 寡聚体的水平。随后，将 IAPP 寡聚化水平定义为通过 sFIDA 确定的 IAPP 寡聚物与通过 ELISA 确定的总 IAPP 浓度之间的比值。在没有晚期并发症且没有胰岛素治疗的 T2D 患者的血浆中检测到最高的寡聚化水平。其水平与对照组相比明显突出。健康对照组的血浆中呈现出最低的寡聚化水平。在没有并发症的 T2D 患者中，IAPP 寡聚化水平与疾病持续时间相关。结果清楚地表明，胰岛素初治患者的 IAPP 寡聚化与 T2D 的持续时间相关。尽管相关性本身不能确定哪个是原因，哪个是结果，但这一结果支持了 IAPP 聚集是 T2D 发展和进展的驱动因素的假设。替代和传统的假设用胰岛素抵抗的增加来解释 T2D 的发展，导致由于胰岛素过度分泌而耗尽胰腺β细胞，因此 IAPP 也是如此，导致随后在胰腺中 IAPP 聚集和纤维沉积。需要进行进一步的实验和与原发性组织的比较分析。
