Isolated pancreatic islet yield and quality is inversely related to organ donor age in rats
Isolated pancreatic islet yield and quality is inversely related to organ donor age in rats
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DOI：
10.1016/j.exger.2019.110739
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发表时间：
2019-12-01
影响因子：
3.9
通讯作者：
Komatsu, Hirotake
中科院分区：
文献类型：
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作者：
Gonzalez, Nelson;Salgado, Mayra;Komatsu, Hirotake
胰岛由几种维持葡萄糖稳态的内分泌细胞组成。1型糖尿病（T1 D）是由自身免疫介导的胰岛中产生胰岛素的β细胞的破坏引起的。胰岛移植是治疗某些T1 D患者的一种方法。啮齿动物胰岛移植作为临床的实验模型，需要胰岛数量和质量的一致性以获得可重复的结果。本研究对不同年龄大鼠胰岛的产量和功能进行了研究。从年轻（10-20周龄）、中间（21-40周龄）和老年（> 41周龄）雄性大鼠收获胰腺，并使用标准方案分离胰岛。对胰岛数量、形态测定、活力、功能和代谢进行了表征。胰岛产量，标准化为体重，作为增加供体年龄的函数下降。来自年轻动物胰腺的胰岛比来自中龄和老龄动物器官的胰岛更大且碎片更少。过夜培养后的胰岛活力对于来自年轻和中等年龄供体的胰岛是相同的，但对于来自老年供体的胰岛则较低。在老年供体的胰岛中，葡萄糖刺激的胰岛素分泌减少。胰岛代谢葡萄糖挑战后，测量的耗氧量，显示，胰岛从老年捐助者代谢较慢，滞后于葡萄糖刺激。这些数据表明，供体年龄的增加对分离的胰岛产量和质量有负面影响。
Pancreatic islets consist of several endocrine cell types that maintain glucose homeostasis. Type 1 diabetes (T1D) results from autoimmune-mediated destruction of insulin producing beta cells in pancreatic islets. Islet transplantation is a treatment for certain individuals with T1D. Islet transplantation in rodents, as an experimental model of the clinical scenario, requires consistency of islet quantity and quality to obtain reproducible results. In this study, we investigated the yield and function of the isolated islets from rats of different ages. Pancreata were harvested from young (10-20 week-old), intermediate (21-40 week-old) and old (> 41 week-old) male rats and islets were isolated using a standard protocol. Islet number, morphometry, viability, function, and metabolism were characterized. Islet yield, normalized to body weight, decreased as a function of increasing donor age. Islets from pancreata from young animals were larger and less fragmented compared to islets from organs from intermediate and older animals. Islet viability following overnight culture was the same for islets derived from young and intermediate aged donors but less for islets from old donors. Glucose-stimulated insulin secretion was decreased in islets from older donors. Islet metabolism following glucose challenge, as measured by oxygen consumption, revealed that islets from old donors were metabolically slower and lagged in response to glucose-stimuli. These data demonstrate that increasing donor age has a negative impact on isolated islet yield and quality.