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2 型糖尿病器官捐献者胰岛制备物的研究特点。

Characteristics of research-focused human islet preparations from organ donors with type 2 diabetes.

机构信息

Research Institute of Transplant Medicine, Tianjin First Central Hospital, Nankai University, Tianjin, China.

NHC Key Laboratory for Critical Care Medicine, Tianjin First Central Hospital, Tianjin, China.

出版信息

Islets. 2023 Dec 31;15(1):2219104. doi: 10.1080/19382014.2023.2219104.

Abstract

Type 2 diabetes mellitus (T2D) affects 463 million individuals worldwide. β-cell dysfunction and relatively inadequate β-cell mass has been implicated in the pathogenesis of T2D. Primary human islets from T2D patients can reveal the islet dysfunction and the underlying mechanisms and thus have become valued resources for diabetes research. Our center (Human Islet Resource Center, China) has prepared a number of batches of human islets from T2D organ donors. The present study aims to characterize islet isolation processes, islet yields, and qualities of T2D pancreases by comparing with non-diabetic (ND) ones. Overall, 24 T2D and 80 ND pancreases were obtained with informed research consents. The digestion time, islet purity, yield, size distribution, islet morphology score, viability, and function in each islet preparation were analyzed. We found that at digestion stage, T2D pancreases need significantly longer digestion duration and have worse digestion rates and lower gross islet yields. At purification stage, T2D pancreases have poorer purity, purification rate, morphology score, and islet yields after purification. Functional evaluation by GSI assay showed that the human T2D islets have significantly lower glucose stimulated insulin secretion ability. In conclusion, the features of longer digestion duration, lower yields and quality, and impaired insulin secretion in T2D group are consistent with the pathological condition of this disease. Both islet yields and islet function evaluation results did not support human T2D islets as clinical transplantation resources. However, they could serve as good research models for T2D disease studies and promote the advancement of diabetes research.

摘要

2 型糖尿病(T2D)影响着全球 4.63 亿人。β 细胞功能障碍和相对不足的β细胞量被认为与 T2D 的发病机制有关。来自 T2D 患者的原代人胰岛可以揭示胰岛功能障碍及其潜在机制,因此已成为糖尿病研究的宝贵资源。我们中心(中国胰岛资源中心)已经从 T2D 器官捐献者中制备了多批人胰岛。本研究旨在通过与非糖尿病(ND)胰岛比较,描述 T2D 胰腺的胰岛分离过程、胰岛产量和质量。总体而言,在知情同意的情况下,获得了 24 个 T2D 胰腺和 80 个 ND 胰腺。分析了每个胰岛制备物的消化时间、胰岛纯度、产量、大小分布、胰岛形态评分、活力和功能。我们发现,在消化阶段,T2D 胰腺需要更长的消化时间,消化率和总胰岛产量更低。在纯化阶段,T2D 胰腺的纯度、纯化率、形态评分和纯化后的胰岛产量较差。GSI 测定的功能评估表明,人 T2D 胰岛的葡萄糖刺激胰岛素分泌能力明显降低。总之,T2D 组消化时间长、产量和质量低、胰岛素分泌受损的特征与该疾病的病理状况一致。胰岛产量和胰岛功能评估结果均不支持将人 T2D 胰岛作为临床移植资源。然而,它们可以作为 T2D 疾病研究的良好研究模型,并促进糖尿病研究的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9027/10269413/0d7c952fabcd/KISL_A_2219104_UF0001_OC.jpg

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